2011 ASCO Annual Meeting

CHICAGO – Adding regional nodal irradiation to whole-breast irradiation significantly improved disease-free survival, but not overall survival in a randomized multi-center phase III trial of women with node-positive or high-risk node-negative disease treated with breast-conserving surgery and adjuvant therapy.

An interim analysis of 1,832 women with breast cancer found that after a median follow-up of 62 months, whole breast irradiation (WBI) plus regional nodal irradiation (RNI) significantly reduced the risk of locoregional recurrence from 5.5% to 3.2% (P = .02; hazard ratio 0.8) and distant recurrence from 13% to 7.6% (P = .002; HR 0.64), lead investigator Dr. Timothy Whelan reported at the annual meeting of the American Society of Clinical Oncology.

Overall survival in the intergroup trial was 9.3% with WBI vs. 7.7% with the combined radiation regimen, but the difference did not reach statistical significance (P = .07; HR 0.76).

In view of the positive findings, the data safety monitoring committee recommended that the results be released, Dr. Whelan told reporters at a press briefing during the meeting.

He suggested that the findings could expand the pool of women offered RNI. Currently, ASCO and the American Society for Therapeutic Radiology and Oncology (ASTRO) guidelines recommend locoregional radiation following mastectomy for tumors greater than 5 cm or with more than three positive axillary nodes.

Of the 1,832 women enrolled in the National Cancer Institute of Canada Clinical Trials Group MA.20 trial, 85% had one to three positive lymph nodes, and 10% had high-risk, node-negative breast cancer. All women were treated with breast-conserving surgery plus adjuvant chemotherapy or endocrine therapy.

"Results from MA.20 suggest that all women with node-positive disease be offered regional node irradiation provided they are made aware of the associated toxicities," said Dr. Whelan, head of radiation oncology at McMaster University and the Juravinski Cancer Centre, Hamilton, Ont.

The addition of RNI to WBI significantly increased the rates of grade 2 or higher dermatitis from 40% to 50% (P less than .001), pneumonitis from 0.2% to 1.3% (P = .01), and lymphedema from 4% to 7% (P = .004). The lymphedema was primarily grade 2, Dr. Whelen pointed out.

Reporters questioned why an earlier unpublished French study did not find a benefit with RNI, while MA.20 did. Dr. Whelan responded that regional radiation in the earlier study was limited to the internal mammary lymph nodes alone, whereas MA.20 expanded the upper radiation field to include the upper internal mammary nodes, supraclavicular nodes, and high axillary nodes. He could not explain why overall survival was not improved.

Radiation dosages for WBI were 50 Gy in 25 fractions plus a boost at the discretion of the cancer center of 10 Gy in 5 fractions. The RNI dosage was 45 Gy in 25 fractions.

WBI and RNI were delivered concurrently, so the added therapy would not require additional office visits for women, and would modestly lengthen the therapy.

The researchers will continue to monitor the patients and evaluate new techniques to reduce potential side effects, he said in an interview.

MA.20 was sponsored by the Canadian Cancer Society Research Institute, National Cancer Institute/Cancer Therapy Evaluation Program, and Canadian Breast Cancer Research Alliance. Dr. Whelan and his coauthors disclosed no conflicts of interest.

CHICAGO – Adding regional nodal irradiation to whole-breast irradiation significantly improved disease-free survival, but not overall survival in a randomized multi-center phase III trial of women with node-positive or high-risk node-negative disease treated with breast-conserving surgery and adjuvant therapy.

An interim analysis of 1,832 women with breast cancer found that after a median follow-up of 62 months, whole breast irradiation (WBI) plus regional nodal irradiation (RNI) significantly reduced the risk of locoregional recurrence from 5.5% to 3.2% (P = .02; hazard ratio 0.8) and distant recurrence from 13% to 7.6% (P = .002; HR 0.64), lead investigator Dr. Timothy Whelan reported at the annual meeting of the American Society of Clinical Oncology.

Overall survival in the intergroup trial was 9.3% with WBI vs. 7.7% with the combined radiation regimen, but the difference did not reach statistical significance (P = .07; HR 0.76).

In view of the positive findings, the data safety monitoring committee recommended that the results be released, Dr. Whelan told reporters at a press briefing during the meeting.

He suggested that the findings could expand the pool of women offered RNI. Currently, ASCO and the American Society for Therapeutic Radiology and Oncology (ASTRO) guidelines recommend locoregional radiation following mastectomy for tumors greater than 5 cm or with more than three positive axillary nodes.

Of the 1,832 women enrolled in the National Cancer Institute of Canada Clinical Trials Group MA.20 trial, 85% had one to three positive lymph nodes, and 10% had high-risk, node-negative breast cancer. All women were treated with breast-conserving surgery plus adjuvant chemotherapy or endocrine therapy.

"Results from MA.20 suggest that all women with node-positive disease be offered regional node irradiation provided they are made aware of the associated toxicities," said Dr. Whelan, head of radiation oncology at McMaster University and the Juravinski Cancer Centre, Hamilton, Ont.

The addition of RNI to WBI significantly increased the rates of grade 2 or higher dermatitis from 40% to 50% (P less than .001), pneumonitis from 0.2% to 1.3% (P = .01), and lymphedema from 4% to 7% (P = .004). The lymphedema was primarily grade 2, Dr. Whelen pointed out.

Reporters questioned why an earlier unpublished French study did not find a benefit with RNI, while MA.20 did. Dr. Whelan responded that regional radiation in the earlier study was limited to the internal mammary lymph nodes alone, whereas MA.20 expanded the upper radiation field to include the upper internal mammary nodes, supraclavicular nodes, and high axillary nodes. He could not explain why overall survival was not improved.

Radiation dosages for WBI were 50 Gy in 25 fractions plus a boost at the discretion of the cancer center of 10 Gy in 5 fractions. The RNI dosage was 45 Gy in 25 fractions.

WBI and RNI were delivered concurrently, so the added therapy would not require additional office visits for women, and would modestly lengthen the therapy.

The researchers will continue to monitor the patients and evaluate new techniques to reduce potential side effects, he said in an interview.

MA.20 was sponsored by the Canadian Cancer Society Research Institute, National Cancer Institute/Cancer Therapy Evaluation Program, and Canadian Breast Cancer Research Alliance. Dr. Whelan and his coauthors disclosed no conflicts of interest.

CHICAGO – Adding regional nodal irradiation to whole-breast irradiation significantly improved disease-free survival, but not overall survival in a randomized multi-center phase III trial of women with node-positive or high-risk node-negative disease treated with breast-conserving surgery and adjuvant therapy.

An interim analysis of 1,832 women with breast cancer found that after a median follow-up of 62 months, whole breast irradiation (WBI) plus regional nodal irradiation (RNI) significantly reduced the risk of locoregional recurrence from 5.5% to 3.2% (P = .02; hazard ratio 0.8) and distant recurrence from 13% to 7.6% (P = .002; HR 0.64), lead investigator Dr. Timothy Whelan reported at the annual meeting of the American Society of Clinical Oncology.

Overall survival in the intergroup trial was 9.3% with WBI vs. 7.7% with the combined radiation regimen, but the difference did not reach statistical significance (P = .07; HR 0.76).

In view of the positive findings, the data safety monitoring committee recommended that the results be released, Dr. Whelan told reporters at a press briefing during the meeting.

He suggested that the findings could expand the pool of women offered RNI. Currently, ASCO and the American Society for Therapeutic Radiology and Oncology (ASTRO) guidelines recommend locoregional radiation following mastectomy for tumors greater than 5 cm or with more than three positive axillary nodes.

Of the 1,832 women enrolled in the National Cancer Institute of Canada Clinical Trials Group MA.20 trial, 85% had one to three positive lymph nodes, and 10% had high-risk, node-negative breast cancer. All women were treated with breast-conserving surgery plus adjuvant chemotherapy or endocrine therapy.

"Results from MA.20 suggest that all women with node-positive disease be offered regional node irradiation provided they are made aware of the associated toxicities," said Dr. Whelan, head of radiation oncology at McMaster University and the Juravinski Cancer Centre, Hamilton, Ont.

The addition of RNI to WBI significantly increased the rates of grade 2 or higher dermatitis from 40% to 50% (P less than .001), pneumonitis from 0.2% to 1.3% (P = .01), and lymphedema from 4% to 7% (P = .004). The lymphedema was primarily grade 2, Dr. Whelen pointed out.

Reporters questioned why an earlier unpublished French study did not find a benefit with RNI, while MA.20 did. Dr. Whelan responded that regional radiation in the earlier study was limited to the internal mammary lymph nodes alone, whereas MA.20 expanded the upper radiation field to include the upper internal mammary nodes, supraclavicular nodes, and high axillary nodes. He could not explain why overall survival was not improved.

Radiation dosages for WBI were 50 Gy in 25 fractions plus a boost at the discretion of the cancer center of 10 Gy in 5 fractions. The RNI dosage was 45 Gy in 25 fractions.

WBI and RNI were delivered concurrently, so the added therapy would not require additional office visits for women, and would modestly lengthen the therapy.

The researchers will continue to monitor the patients and evaluate new techniques to reduce potential side effects, he said in an interview.

MA.20 was sponsored by the Canadian Cancer Society Research Institute, National Cancer Institute/Cancer Therapy Evaluation Program, and Canadian Breast Cancer Research Alliance. Dr. Whelan and his coauthors disclosed no conflicts of interest.

CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program.

If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.

The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.

Consequently, the overall incidence of oropharyngeal cancers increased 28%.

Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.

Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.

Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study. A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).

The evidence surrounding HPV-related oral cancers has been mounting, "but I don’t think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.

Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients’ partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.

"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they’ve already swapped. Just because they suddenly found that one of them got cancer from it doesn’t mean the other one will."

The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.

Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.

It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.

Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.

"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."

In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.

The HPV prevalence in oropharyngeal cancer significantly increased across the time period, regardless of the assay used, and remained statistically significant, even after correcting for potential loss in assay sensitivity, Dr. Gillison reported. Genotyping with the Inno-LiPA assay appeared to be the most precise, detecting more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.

Median survival was significantly better for patients with HPV-positive cancer at 131 months vs. 20 months for HPV-negative patients (log rank P value less than .001). HPV-positive cases on all assays had a significant reduction in hazard of death compared with HPV-negative cases after adjustment for age, sex, race, registry, calendar period, stage, surgery, chemotherapy, and radiotherapy.

Survival of HPV-positive cases increased over the study period but remained unchanged for HPV-negative cases. Consequently, survival of all oropharyngeal cancer cases improved over time, according to the results of the study, which was led by Dr. Amil Chaturvedi, an investigator with the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.

CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program.

If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.

The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.

Consequently, the overall incidence of oropharyngeal cancers increased 28%.

Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.

Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.

Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study. A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).

The evidence surrounding HPV-related oral cancers has been mounting, "but I don’t think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.

Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients’ partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.

"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they’ve already swapped. Just because they suddenly found that one of them got cancer from it doesn’t mean the other one will."

The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.

Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.

It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.

Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.

"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."

In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.

The HPV prevalence in oropharyngeal cancer significantly increased across the time period, regardless of the assay used, and remained statistically significant, even after correcting for potential loss in assay sensitivity, Dr. Gillison reported. Genotyping with the Inno-LiPA assay appeared to be the most precise, detecting more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.

Median survival was significantly better for patients with HPV-positive cancer at 131 months vs. 20 months for HPV-negative patients (log rank P value less than .001). HPV-positive cases on all assays had a significant reduction in hazard of death compared with HPV-negative cases after adjustment for age, sex, race, registry, calendar period, stage, surgery, chemotherapy, and radiotherapy.

Survival of HPV-positive cases increased over the study period but remained unchanged for HPV-negative cases. Consequently, survival of all oropharyngeal cancer cases improved over time, according to the results of the study, which was led by Dr. Amil Chaturvedi, an investigator with the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.

CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program.

If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.

The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.

Consequently, the overall incidence of oropharyngeal cancers increased 28%.

Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.

Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.

Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study. A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).

The evidence surrounding HPV-related oral cancers has been mounting, "but I don’t think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.

Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients’ partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.

"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they’ve already swapped. Just because they suddenly found that one of them got cancer from it doesn’t mean the other one will."

The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.

Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.

It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.

Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.

"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."

In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.

The HPV prevalence in oropharyngeal cancer significantly increased across the time period, regardless of the assay used, and remained statistically significant, even after correcting for potential loss in assay sensitivity, Dr. Gillison reported. Genotyping with the Inno-LiPA assay appeared to be the most precise, detecting more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.

Median survival was significantly better for patients with HPV-positive cancer at 131 months vs. 20 months for HPV-negative patients (log rank P value less than .001). HPV-positive cases on all assays had a significant reduction in hazard of death compared with HPV-negative cases after adjustment for age, sex, race, registry, calendar period, stage, surgery, chemotherapy, and radiotherapy.

Survival of HPV-positive cases increased over the study period but remained unchanged for HPV-negative cases. Consequently, survival of all oropharyngeal cancer cases improved over time, according to the results of the study, which was led by Dr. Amil Chaturvedi, an investigator with the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.

CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program.

If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.

The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.

Consequently, the overall incidence of oropharyngeal cancers increased 28%.

Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.

Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.

Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study. A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).

The evidence surrounding HPV-related oral cancers has been mounting, "but I don’t think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.

Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients’ partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.

"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they’ve already swapped. Just because they suddenly found that one of them got cancer from it doesn’t mean the other one will."

The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.

Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.

It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.

Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.

"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."

In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.

The HPV prevalence in oropharyngeal cancer significantly increased across the time period, regardless of the assay used, and remained statistically significant, even after correcting for potential loss in assay sensitivity, Dr. Gillison reported. Genotyping with the Inno-LiPA assay appeared to be the most precise, detecting more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.

Median survival was significantly better for patients with HPV-positive cancer at 131 months vs. 20 months for HPV-negative patients (log rank P value less than .001). HPV-positive cases on all assays had a significant reduction in hazard of death compared with HPV-negative cases after adjustment for age, sex, race, registry, calendar period, stage, surgery, chemotherapy, and radiotherapy.

Survival of HPV-positive cases increased over the study period but remained unchanged for HPV-negative cases. Consequently, survival of all oropharyngeal cancer cases improved over time, according to the results of the study, which was led by Dr. Amil Chaturvedi, an investigator with the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.

CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program.

If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.

The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.

Consequently, the overall incidence of oropharyngeal cancers increased 28%.

Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.

Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.

Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study. A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).

The evidence surrounding HPV-related oral cancers has been mounting, "but I don’t think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.

Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients’ partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.

"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they’ve already swapped. Just because they suddenly found that one of them got cancer from it doesn’t mean the other one will."

The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.

Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.

It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.

Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.

"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."

In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.

The HPV prevalence in oropharyngeal cancer significantly increased across the time period, regardless of the assay used, and remained statistically significant, even after correcting for potential loss in assay sensitivity, Dr. Gillison reported. Genotyping with the Inno-LiPA assay appeared to be the most precise, detecting more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.

Median survival was significantly better for patients with HPV-positive cancer at 131 months vs. 20 months for HPV-negative patients (log rank P value less than .001). HPV-positive cases on all assays had a significant reduction in hazard of death compared with HPV-negative cases after adjustment for age, sex, race, registry, calendar period, stage, surgery, chemotherapy, and radiotherapy.

Survival of HPV-positive cases increased over the study period but remained unchanged for HPV-negative cases. Consequently, survival of all oropharyngeal cancer cases improved over time, according to the results of the study, which was led by Dr. Amil Chaturvedi, an investigator with the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.

CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program.

If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.

The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.

Consequently, the overall incidence of oropharyngeal cancers increased 28%.

Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.

Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.

Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study. A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).

The evidence surrounding HPV-related oral cancers has been mounting, "but I don’t think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.

Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients’ partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.

"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they’ve already swapped. Just because they suddenly found that one of them got cancer from it doesn’t mean the other one will."

The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.

Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.

It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.

Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.

"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."

In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.

The HPV prevalence in oropharyngeal cancer significantly increased across the time period, regardless of the assay used, and remained statistically significant, even after correcting for potential loss in assay sensitivity, Dr. Gillison reported. Genotyping with the Inno-LiPA assay appeared to be the most precise, detecting more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.

Median survival was significantly better for patients with HPV-positive cancer at 131 months vs. 20 months for HPV-negative patients (log rank P value less than .001). HPV-positive cases on all assays had a significant reduction in hazard of death compared with HPV-negative cases after adjustment for age, sex, race, registry, calendar period, stage, surgery, chemotherapy, and radiotherapy.

Survival of HPV-positive cases increased over the study period but remained unchanged for HPV-negative cases. Consequently, survival of all oropharyngeal cancer cases improved over time, according to the results of the study, which was led by Dr. Amil Chaturvedi, an investigator with the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.

CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program.

If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.

The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.

Consequently, the overall incidence of oropharyngeal cancers increased 28%.

Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.

Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.

Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study. A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).

The evidence surrounding HPV-related oral cancers has been mounting, "but I don’t think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.

Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients’ partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.

"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they’ve already swapped. Just because they suddenly found that one of them got cancer from it doesn’t mean the other one will."

The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.

Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.

It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.

Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.

"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."

In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.

The HPV prevalence in oropharyngeal cancer significantly increased across the time period, regardless of the assay used, and remained statistically significant, even after correcting for potential loss in assay sensitivity, Dr. Gillison reported. Genotyping with the Inno-LiPA assay appeared to be the most precise, detecting more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.

Median survival was significantly better for patients with HPV-positive cancer at 131 months vs. 20 months for HPV-negative patients (log rank P value less than .001). HPV-positive cases on all assays had a significant reduction in hazard of death compared with HPV-negative cases after adjustment for age, sex, race, registry, calendar period, stage, surgery, chemotherapy, and radiotherapy.

Survival of HPV-positive cases increased over the study period but remained unchanged for HPV-negative cases. Consequently, survival of all oropharyngeal cancer cases improved over time, according to the results of the study, which was led by Dr. Amil Chaturvedi, an investigator with the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.

CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program.

If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.

The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.

Consequently, the overall incidence of oropharyngeal cancers increased 28%.

Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.

Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.

Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study. A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).

The evidence surrounding HPV-related oral cancers has been mounting, "but I don’t think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.

Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients’ partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.

"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they’ve already swapped. Just because they suddenly found that one of them got cancer from it doesn’t mean the other one will."

The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.

Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.

It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.

Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.

"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."

In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.

The HPV prevalence in oropharyngeal cancer significantly increased across the time period, regardless of the assay used, and remained statistically significant, even after correcting for potential loss in assay sensitivity, Dr. Gillison reported. Genotyping with the Inno-LiPA assay appeared to be the most precise, detecting more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.

Median survival was significantly better for patients with HPV-positive cancer at 131 months vs. 20 months for HPV-negative patients (log rank P value less than .001). HPV-positive cases on all assays had a significant reduction in hazard of death compared with HPV-negative cases after adjustment for age, sex, race, registry, calendar period, stage, surgery, chemotherapy, and radiotherapy.

Survival of HPV-positive cases increased over the study period but remained unchanged for HPV-negative cases. Consequently, survival of all oropharyngeal cancer cases improved over time, according to the results of the study, which was led by Dr. Amil Chaturvedi, an investigator with the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.

CHICAGO – Human papillomavirus infection was firmly linked to the recent rise in oropharyngeal cancers in the United States, based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program.

If current trends continue, the incidence of HPV-related oral cancers will soon surpass that of cervical cancers, senior author Dr. Maura Gillison reported at the annual meeting of the American Society of Clinical Oncology.

The incidence of HPV-positive oropharyngeal cancers increased 225% – from 0.8 per 100,000 to 2.8 per 100,000 – between 1988 and 2004, the researchers found. At the same time, the incidence rate for HPV-negative oropharyngeal cancers, which are strongly related to tobacco and alcohol use, declined by 50% – from 2.0 per 100,000 to 1.0 per 100,000.

Consequently, the overall incidence of oropharyngeal cancers increased 28%.

Even by the conservative estimate that 70% of oropharyngeal cancers in 2020 will be HPV positive, the annual number of HPV-positive oral squamous cell carcinomas (8,653 cases) is expected to surpass cervical cancers (7,726 cases). Further, the majority will occur among men (7,426 cases), said Dr. Gillison, a medical oncologist and the Jeg Coughlin Chair in Cancer Research at Ohio State University Comprehensive Cancer Center in Columbus.

Changes in sexual behavior among recent birth cohorts and increased oral HPV exposure probably influenced the increases in incidence and prevalence, Dr. Gillison speculated. Having a high lifetime number of sexual partners is a known risk factor for HPV infection.

Although the rise in oral cancers in the United States has been attributed to HPV infection, the empirical evidence to back the contention was uncovered prior to the SEER study. A previous study by Dr. Gillison and her colleagues helped to establish that HPV infection causes an epidemiologically and clinically different form of oral cancer. Their findings documented a major increase in the incidence of HPV-related oral cancers in the United States, particularly among young, white men, and that survival rates are significantly higher in patients with HPV-related oral cancers than in those with HPV-negative cancers (J. Clin. Oncol. 2008;26:612-9).

The evidence surrounding HPV-related oral cancers has been mounting, "but I don’t think there is a lot of awareness in the general medical community," Dr. Gillison said in an interview. Most of her head-and-neck cancer patients who are nonsmokers were referred to her after undergoing months of antibiotic therapy for presumed tonsillitis.

Screening the sexual partners of oropharyngeal cancer patients has been discussed, but there is no evidence to support the practice. The risk for oral cancer is fourfold higher in HPV-positive patients’ partners, but the absolute risk is low, Dr. Gillison said. Alternatively, there are now three or four case reports of husband-wife couples with HPV16-positive tonsillar cancer.

"Probably 80% of people have HPV exposures in their life and 99.1% clear the infections without consequence," she said. "So, whatever [stable sexual partners] have swapped in terms of infection, they’ve already swapped. Just because they suddenly found that one of them got cancer from it doesn’t mean the other one will."

The researchers called for more studies to evaluate the efficacy of HPV vaccines in preventing oral HPV infections.

Dr. Gillison worked for 3 years with Merck & Co., the maker of the HPV vaccine Gardasil, and commented that Merck will not likely pursue this indication. Merck was interested in studying the vaccine in prevention of oral cancers but saw the endeavor as too much of an uphill battle in part because oral cancers are not readily accessible visibly or through biopsy. Merck instead successfully opted to seek approval for the prevention of anal cancers, an indication that was approved in December 2010 for male and females 9-26 years old.

It was already approved in the same age groups for the prevention of cervical, vulvar, and vaginal cancer and of genital warts caused by HPV types 6, 11, 16, and 18 in females and for the prevention of genital warts caused by HPV types 6 and 11 in males.

Invited discussant Dr. Lisa Licitra of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, said that oral cancers are on the rise in Europe in both men and women and that a vaccine should be pursued. Data on oropharyngeal cancer from her institute did not find a greater contribution from men.

"A preventive vaccine is worth considering," she said. "In particular, when we consider the European data, I think that in this direction, action should be taken."

In their study, Dr. Gillison and her colleagues used four different assays to determine the HPV status for 271 oropharyngeal cancer cases collected from 1984 to 2004 by three population-based cancer registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results program in Hawaii, Iowa, and Los Angeles. Trends in HPV prevalence across four calendar periods were estimated using logistic regression.

The HPV prevalence in oropharyngeal cancer significantly increased across the time period, regardless of the assay used, and remained statistically significant, even after correcting for potential loss in assay sensitivity, Dr. Gillison reported. Genotyping with the Inno-LiPA assay appeared to be the most precise, detecting more than a fourfold increase in HPV prevalence from 16.3% in 1984-1989 to 72.7% in 2000-2004.

Median survival was significantly better for patients with HPV-positive cancer at 131 months vs. 20 months for HPV-negative patients (log rank P value less than .001). HPV-positive cases on all assays had a significant reduction in hazard of death compared with HPV-negative cases after adjustment for age, sex, race, registry, calendar period, stage, surgery, chemotherapy, and radiotherapy.

Survival of HPV-positive cases increased over the study period but remained unchanged for HPV-negative cases. Consequently, survival of all oropharyngeal cancer cases improved over time, according to the results of the study, which was led by Dr. Amil Chaturvedi, an investigator with the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

Dr. Gillison and Dr. Chaturvedi reported no conflicts of interest. A coauthor disclosed consultancy, research funding, and honoraria from Merck.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO - Screening for ovarian cancer did not reduce the risk of dying from the disease for women with average risk, according to results of a multicenter screening study of nearly 80,000 women.

Screening nearly 40,000 post-menopausal women with transvaginal ultrasound for 4 years and CA-124 for 6 years did not decrease ovarian cancer mortality compared to nearly 40,000 control women. Further, there was evidence of harm in the 3,285 women with false positive results; 1080 women had surgery and 163 of them had 222 major complications, according to Dr. Saundra Buys, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, whose presentation of the data was given on June 4 at the annual meeting of the American Society of Clinical Oncology. The study appears in the June 8 issue of JAMA (2011;305:2295-303). 

Among women who underwent screening, 118 died of ovarian cancer, whereas 100 women who received usual care died as a result of the disease. The difference was not significant.

"It is possible that even an optimized program of annual screening may be insufficient to detect cancers early enough to reduce mortality. Evidence from modeling suggests that aggressive cancers progress rapidly through the early stages, limiting the ability to detect these cancers with yearly screening," Dr. Buys said.

More ovarian cancers were diagnosed in the screened women (212 vs. 176), although this difference was not significant. This suggests "that some of the additional cancers detected by screening were not clinically important and, if left undetected, may never have caused any symptoms or affected the women during their lifetimes," for example, with overdiagnosis, the researchers observed. Stage III and IV cancers were the most common in each group (77% of the screening group and 78% of the usual care group).

The women in this study were part of the PLCO (Prostate, Lung, Colorectal and Ovarian) cancer screening trial. In all, 68,557 women aged 55-74 years were assigned to either annual screening (34,253 women) or usual care (34,304 women) in 1993-2001 and remained in the analysis. Women in the screening arm were offered annual CA 125 testing for 6 years and transvaginal ultrasound for 4 years. Those in the usual care arm were not offered the screening tests. The median follow-up was 12.4 years.

Women with a CA 125 level of 35 U/mL or greater were classified as abnormal. Transvaginal ultrasound was conducted using a 5-7.5 MHz transvaginal probe. Results were considered abnormal if the ovarian volume was greater than 10 cm³, if the cyst volume was greater than 10 cm³, if any solid area or papillary projection extending into the cavity of a cystic ovarian tumor of any size was present, or if any mixed (solid and cystic) component within a cystic ovarian tumor was present.

Both the women and their physicians were notified in writing about suspicious abnormalities found through screening. The women’s primary care physicians were responsible for managing the diagnostic process to assess abnormalities.

Among women in the screening arm, there were a greater number of false positives (3,285 false positives vs. 212 true positives). Of women who had a false positive test, one-third (1,080 women) underwent surgery for biopsy to evaluate positive test results. Of these, 163 (15%) women had 222 distinct major complications.

One of the authors, Jonathan D. Clapp, reported having a financial interest in Human Genome Sciences Inc. The other authors reported that they had no relevant financial relationships. The National Cancer Institute funded the PLCO cancer screening trial.

Kerri Wachter contributed to this article.

CHICAGO - Screening for ovarian cancer did not reduce the risk of dying from the disease for women with average risk, according to results of a multicenter screening study of nearly 80,000 women.

Screening nearly 40,000 post-menopausal women with transvaginal ultrasound for 4 years and CA-124 for 6 years did not decrease ovarian cancer mortality compared to nearly 40,000 control women. Further, there was evidence of harm in the 3,285 women with false positive results; 1080 women had surgery and 163 of them had 222 major complications, according to Dr. Saundra Buys, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, whose presentation of the data was given on June 4 at the annual meeting of the American Society of Clinical Oncology. The study appears in the June 8 issue of JAMA (2011;305:2295-303). 

Among women who underwent screening, 118 died of ovarian cancer, whereas 100 women who received usual care died as a result of the disease. The difference was not significant.

"It is possible that even an optimized program of annual screening may be insufficient to detect cancers early enough to reduce mortality. Evidence from modeling suggests that aggressive cancers progress rapidly through the early stages, limiting the ability to detect these cancers with yearly screening," Dr. Buys said.

More ovarian cancers were diagnosed in the screened women (212 vs. 176), although this difference was not significant. This suggests "that some of the additional cancers detected by screening were not clinically important and, if left undetected, may never have caused any symptoms or affected the women during their lifetimes," for example, with overdiagnosis, the researchers observed. Stage III and IV cancers were the most common in each group (77% of the screening group and 78% of the usual care group).

The women in this study were part of the PLCO (Prostate, Lung, Colorectal and Ovarian) cancer screening trial. In all, 68,557 women aged 55-74 years were assigned to either annual screening (34,253 women) or usual care (34,304 women) in 1993-2001 and remained in the analysis. Women in the screening arm were offered annual CA 125 testing for 6 years and transvaginal ultrasound for 4 years. Those in the usual care arm were not offered the screening tests. The median follow-up was 12.4 years.

Women with a CA 125 level of 35 U/mL or greater were classified as abnormal. Transvaginal ultrasound was conducted using a 5-7.5 MHz transvaginal probe. Results were considered abnormal if the ovarian volume was greater than 10 cm³, if the cyst volume was greater than 10 cm³, if any solid area or papillary projection extending into the cavity of a cystic ovarian tumor of any size was present, or if any mixed (solid and cystic) component within a cystic ovarian tumor was present.

Both the women and their physicians were notified in writing about suspicious abnormalities found through screening. The women’s primary care physicians were responsible for managing the diagnostic process to assess abnormalities.

Among women in the screening arm, there were a greater number of false positives (3,285 false positives vs. 212 true positives). Of women who had a false positive test, one-third (1,080 women) underwent surgery for biopsy to evaluate positive test results. Of these, 163 (15%) women had 222 distinct major complications.

One of the authors, Jonathan D. Clapp, reported having a financial interest in Human Genome Sciences Inc. The other authors reported that they had no relevant financial relationships. The National Cancer Institute funded the PLCO cancer screening trial.

Kerri Wachter contributed to this article.

CHICAGO - Screening for ovarian cancer did not reduce the risk of dying from the disease for women with average risk, according to results of a multicenter screening study of nearly 80,000 women.

Screening nearly 40,000 post-menopausal women with transvaginal ultrasound for 4 years and CA-124 for 6 years did not decrease ovarian cancer mortality compared to nearly 40,000 control women. Further, there was evidence of harm in the 3,285 women with false positive results; 1080 women had surgery and 163 of them had 222 major complications, according to Dr. Saundra Buys, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, whose presentation of the data was given on June 4 at the annual meeting of the American Society of Clinical Oncology. The study appears in the June 8 issue of JAMA (2011;305:2295-303). 

Among women who underwent screening, 118 died of ovarian cancer, whereas 100 women who received usual care died as a result of the disease. The difference was not significant.

"It is possible that even an optimized program of annual screening may be insufficient to detect cancers early enough to reduce mortality. Evidence from modeling suggests that aggressive cancers progress rapidly through the early stages, limiting the ability to detect these cancers with yearly screening," Dr. Buys said.

More ovarian cancers were diagnosed in the screened women (212 vs. 176), although this difference was not significant. This suggests "that some of the additional cancers detected by screening were not clinically important and, if left undetected, may never have caused any symptoms or affected the women during their lifetimes," for example, with overdiagnosis, the researchers observed. Stage III and IV cancers were the most common in each group (77% of the screening group and 78% of the usual care group).

The women in this study were part of the PLCO (Prostate, Lung, Colorectal and Ovarian) cancer screening trial. In all, 68,557 women aged 55-74 years were assigned to either annual screening (34,253 women) or usual care (34,304 women) in 1993-2001 and remained in the analysis. Women in the screening arm were offered annual CA 125 testing for 6 years and transvaginal ultrasound for 4 years. Those in the usual care arm were not offered the screening tests. The median follow-up was 12.4 years.

Women with a CA 125 level of 35 U/mL or greater were classified as abnormal. Transvaginal ultrasound was conducted using a 5-7.5 MHz transvaginal probe. Results were considered abnormal if the ovarian volume was greater than 10 cm³, if the cyst volume was greater than 10 cm³, if any solid area or papillary projection extending into the cavity of a cystic ovarian tumor of any size was present, or if any mixed (solid and cystic) component within a cystic ovarian tumor was present.

Both the women and their physicians were notified in writing about suspicious abnormalities found through screening. The women’s primary care physicians were responsible for managing the diagnostic process to assess abnormalities.

Among women in the screening arm, there were a greater number of false positives (3,285 false positives vs. 212 true positives). Of women who had a false positive test, one-third (1,080 women) underwent surgery for biopsy to evaluate positive test results. Of these, 163 (15%) women had 222 distinct major complications.

One of the authors, Jonathan D. Clapp, reported having a financial interest in Human Genome Sciences Inc. The other authors reported that they had no relevant financial relationships. The National Cancer Institute funded the PLCO cancer screening trial.

Kerri Wachter contributed to this article.

CHICAGO - Screening for ovarian cancer did not reduce the risk of dying from the disease for women with average risk, according to results of a multicenter screening study of nearly 80,000 women.

Screening nearly 40,000 post-menopausal women with transvaginal ultrasound for 4 years and CA-124 for 6 years did not decrease ovarian cancer mortality compared to nearly 40,000 control women. Further, there was evidence of harm in the 3,285 women with false positive results; 1080 women had surgery and 163 of them had 222 major complications, according to Dr. Saundra Buys, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, whose presentation of the data was given on June 4 at the annual meeting of the American Society of Clinical Oncology. The study appears in the June 8 issue of JAMA (2011;305:2295-303). 

Among women who underwent screening, 118 died of ovarian cancer, whereas 100 women who received usual care died as a result of the disease. The difference was not significant.

"It is possible that even an optimized program of annual screening may be insufficient to detect cancers early enough to reduce mortality. Evidence from modeling suggests that aggressive cancers progress rapidly through the early stages, limiting the ability to detect these cancers with yearly screening," Dr. Buys said.

More ovarian cancers were diagnosed in the screened women (212 vs. 176), although this difference was not significant. This suggests "that some of the additional cancers detected by screening were not clinically important and, if left undetected, may never have caused any symptoms or affected the women during their lifetimes," for example, with overdiagnosis, the researchers observed. Stage III and IV cancers were the most common in each group (77% of the screening group and 78% of the usual care group).

The women in this study were part of the PLCO (Prostate, Lung, Colorectal and Ovarian) cancer screening trial. In all, 68,557 women aged 55-74 years were assigned to either annual screening (34,253 women) or usual care (34,304 women) in 1993-2001 and remained in the analysis. Women in the screening arm were offered annual CA 125 testing for 6 years and transvaginal ultrasound for 4 years. Those in the usual care arm were not offered the screening tests. The median follow-up was 12.4 years.

Women with a CA 125 level of 35 U/mL or greater were classified as abnormal. Transvaginal ultrasound was conducted using a 5-7.5 MHz transvaginal probe. Results were considered abnormal if the ovarian volume was greater than 10 cm³, if the cyst volume was greater than 10 cm³, if any solid area or papillary projection extending into the cavity of a cystic ovarian tumor of any size was present, or if any mixed (solid and cystic) component within a cystic ovarian tumor was present.

Both the women and their physicians were notified in writing about suspicious abnormalities found through screening. The women’s primary care physicians were responsible for managing the diagnostic process to assess abnormalities.

Among women in the screening arm, there were a greater number of false positives (3,285 false positives vs. 212 true positives). Of women who had a false positive test, one-third (1,080 women) underwent surgery for biopsy to evaluate positive test results. Of these, 163 (15%) women had 222 distinct major complications.

One of the authors, Jonathan D. Clapp, reported having a financial interest in Human Genome Sciences Inc. The other authors reported that they had no relevant financial relationships. The National Cancer Institute funded the PLCO cancer screening trial.

Kerri Wachter contributed to this article.

CHICAGO - Screening for ovarian cancer did not reduce the risk of dying from the disease for women with average risk, according to results of a multicenter screening study of nearly 80,000 women.

Screening nearly 40,000 post-menopausal women with transvaginal ultrasound for 4 years and CA-124 for 6 years did not decrease ovarian cancer mortality compared to nearly 40,000 control women. Further, there was evidence of harm in the 3,285 women with false positive results; 1080 women had surgery and 163 of them had 222 major complications, according to Dr. Saundra Buys, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, whose presentation of the data was given on June 4 at the annual meeting of the American Society of Clinical Oncology. The study appears in the June 8 issue of JAMA (2011;305:2295-303). 

Among women who underwent screening, 118 died of ovarian cancer, whereas 100 women who received usual care died as a result of the disease. The difference was not significant.

"It is possible that even an optimized program of annual screening may be insufficient to detect cancers early enough to reduce mortality. Evidence from modeling suggests that aggressive cancers progress rapidly through the early stages, limiting the ability to detect these cancers with yearly screening," Dr. Buys said.

More ovarian cancers were diagnosed in the screened women (212 vs. 176), although this difference was not significant. This suggests "that some of the additional cancers detected by screening were not clinically important and, if left undetected, may never have caused any symptoms or affected the women during their lifetimes," for example, with overdiagnosis, the researchers observed. Stage III and IV cancers were the most common in each group (77% of the screening group and 78% of the usual care group).

The women in this study were part of the PLCO (Prostate, Lung, Colorectal and Ovarian) cancer screening trial. In all, 68,557 women aged 55-74 years were assigned to either annual screening (34,253 women) or usual care (34,304 women) in 1993-2001 and remained in the analysis. Women in the screening arm were offered annual CA 125 testing for 6 years and transvaginal ultrasound for 4 years. Those in the usual care arm were not offered the screening tests. The median follow-up was 12.4 years.

Women with a CA 125 level of 35 U/mL or greater were classified as abnormal. Transvaginal ultrasound was conducted using a 5-7.5 MHz transvaginal probe. Results were considered abnormal if the ovarian volume was greater than 10 cm³, if the cyst volume was greater than 10 cm³, if any solid area or papillary projection extending into the cavity of a cystic ovarian tumor of any size was present, or if any mixed (solid and cystic) component within a cystic ovarian tumor was present.

Both the women and their physicians were notified in writing about suspicious abnormalities found through screening. The women’s primary care physicians were responsible for managing the diagnostic process to assess abnormalities.

Among women in the screening arm, there were a greater number of false positives (3,285 false positives vs. 212 true positives). Of women who had a false positive test, one-third (1,080 women) underwent surgery for biopsy to evaluate positive test results. Of these, 163 (15%) women had 222 distinct major complications.

One of the authors, Jonathan D. Clapp, reported having a financial interest in Human Genome Sciences Inc. The other authors reported that they had no relevant financial relationships. The National Cancer Institute funded the PLCO cancer screening trial.

Kerri Wachter contributed to this article.

CHICAGO - Screening for ovarian cancer did not reduce the risk of dying from the disease for women with average risk, according to results of a multicenter screening study of nearly 80,000 women.

Screening nearly 40,000 post-menopausal women with transvaginal ultrasound for 4 years and CA-124 for 6 years did not decrease ovarian cancer mortality compared to nearly 40,000 control women. Further, there was evidence of harm in the 3,285 women with false positive results; 1080 women had surgery and 163 of them had 222 major complications, according to Dr. Saundra Buys, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, whose presentation of the data was given on June 4 at the annual meeting of the American Society of Clinical Oncology. The study appears in the June 8 issue of JAMA (2011;305:2295-303). 

Among women who underwent screening, 118 died of ovarian cancer, whereas 100 women who received usual care died as a result of the disease. The difference was not significant.

"It is possible that even an optimized program of annual screening may be insufficient to detect cancers early enough to reduce mortality. Evidence from modeling suggests that aggressive cancers progress rapidly through the early stages, limiting the ability to detect these cancers with yearly screening," Dr. Buys said.

More ovarian cancers were diagnosed in the screened women (212 vs. 176), although this difference was not significant. This suggests "that some of the additional cancers detected by screening were not clinically important and, if left undetected, may never have caused any symptoms or affected the women during their lifetimes," for example, with overdiagnosis, the researchers observed. Stage III and IV cancers were the most common in each group (77% of the screening group and 78% of the usual care group).

The women in this study were part of the PLCO (Prostate, Lung, Colorectal and Ovarian) cancer screening trial. In all, 68,557 women aged 55-74 years were assigned to either annual screening (34,253 women) or usual care (34,304 women) in 1993-2001 and remained in the analysis. Women in the screening arm were offered annual CA 125 testing for 6 years and transvaginal ultrasound for 4 years. Those in the usual care arm were not offered the screening tests. The median follow-up was 12.4 years.

Women with a CA 125 level of 35 U/mL or greater were classified as abnormal. Transvaginal ultrasound was conducted using a 5-7.5 MHz transvaginal probe. Results were considered abnormal if the ovarian volume was greater than 10 cm³, if the cyst volume was greater than 10 cm³, if any solid area or papillary projection extending into the cavity of a cystic ovarian tumor of any size was present, or if any mixed (solid and cystic) component within a cystic ovarian tumor was present.

Both the women and their physicians were notified in writing about suspicious abnormalities found through screening. The women’s primary care physicians were responsible for managing the diagnostic process to assess abnormalities.

Among women in the screening arm, there were a greater number of false positives (3,285 false positives vs. 212 true positives). Of women who had a false positive test, one-third (1,080 women) underwent surgery for biopsy to evaluate positive test results. Of these, 163 (15%) women had 222 distinct major complications.

One of the authors, Jonathan D. Clapp, reported having a financial interest in Human Genome Sciences Inc. The other authors reported that they had no relevant financial relationships. The National Cancer Institute funded the PLCO cancer screening trial.

Kerri Wachter contributed to this article.

CHICAGO - Screening for ovarian cancer did not reduce the risk of dying from the disease for women with average risk, according to results of a multicenter screening study of nearly 80,000 women.

Screening nearly 40,000 post-menopausal women with transvaginal ultrasound for 4 years and CA-124 for 6 years did not decrease ovarian cancer mortality compared to nearly 40,000 control women. Further, there was evidence of harm in the 3,285 women with false positive results; 1080 women had surgery and 163 of them had 222 major complications, according to Dr. Saundra Buys, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, whose presentation of the data was given on June 4 at the annual meeting of the American Society of Clinical Oncology. The study appears in the June 8 issue of JAMA (2011;305:2295-303). 

Among women who underwent screening, 118 died of ovarian cancer, whereas 100 women who received usual care died as a result of the disease. The difference was not significant.

"It is possible that even an optimized program of annual screening may be insufficient to detect cancers early enough to reduce mortality. Evidence from modeling suggests that aggressive cancers progress rapidly through the early stages, limiting the ability to detect these cancers with yearly screening," Dr. Buys said.

More ovarian cancers were diagnosed in the screened women (212 vs. 176), although this difference was not significant. This suggests "that some of the additional cancers detected by screening were not clinically important and, if left undetected, may never have caused any symptoms or affected the women during their lifetimes," for example, with overdiagnosis, the researchers observed. Stage III and IV cancers were the most common in each group (77% of the screening group and 78% of the usual care group).

The women in this study were part of the PLCO (Prostate, Lung, Colorectal and Ovarian) cancer screening trial. In all, 68,557 women aged 55-74 years were assigned to either annual screening (34,253 women) or usual care (34,304 women) in 1993-2001 and remained in the analysis. Women in the screening arm were offered annual CA 125 testing for 6 years and transvaginal ultrasound for 4 years. Those in the usual care arm were not offered the screening tests. The median follow-up was 12.4 years.

Women with a CA 125 level of 35 U/mL or greater were classified as abnormal. Transvaginal ultrasound was conducted using a 5-7.5 MHz transvaginal probe. Results were considered abnormal if the ovarian volume was greater than 10 cm³, if the cyst volume was greater than 10 cm³, if any solid area or papillary projection extending into the cavity of a cystic ovarian tumor of any size was present, or if any mixed (solid and cystic) component within a cystic ovarian tumor was present.

Both the women and their physicians were notified in writing about suspicious abnormalities found through screening. The women’s primary care physicians were responsible for managing the diagnostic process to assess abnormalities.

Among women in the screening arm, there were a greater number of false positives (3,285 false positives vs. 212 true positives). Of women who had a false positive test, one-third (1,080 women) underwent surgery for biopsy to evaluate positive test results. Of these, 163 (15%) women had 222 distinct major complications.

One of the authors, Jonathan D. Clapp, reported having a financial interest in Human Genome Sciences Inc. The other authors reported that they had no relevant financial relationships. The National Cancer Institute funded the PLCO cancer screening trial.

Kerri Wachter contributed to this article.

CHICAGO - Screening for ovarian cancer did not reduce the risk of dying from the disease for women with average risk, according to results of a multicenter screening study of nearly 80,000 women.

Screening nearly 40,000 post-menopausal women with transvaginal ultrasound for 4 years and CA-124 for 6 years did not decrease ovarian cancer mortality compared to nearly 40,000 control women. Further, there was evidence of harm in the 3,285 women with false positive results; 1080 women had surgery and 163 of them had 222 major complications, according to Dr. Saundra Buys, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, whose presentation of the data was given on June 4 at the annual meeting of the American Society of Clinical Oncology. The study appears in the June 8 issue of JAMA (2011;305:2295-303). 

Among women who underwent screening, 118 died of ovarian cancer, whereas 100 women who received usual care died as a result of the disease. The difference was not significant.

"It is possible that even an optimized program of annual screening may be insufficient to detect cancers early enough to reduce mortality. Evidence from modeling suggests that aggressive cancers progress rapidly through the early stages, limiting the ability to detect these cancers with yearly screening," Dr. Buys said.

More ovarian cancers were diagnosed in the screened women (212 vs. 176), although this difference was not significant. This suggests "that some of the additional cancers detected by screening were not clinically important and, if left undetected, may never have caused any symptoms or affected the women during their lifetimes," for example, with overdiagnosis, the researchers observed. Stage III and IV cancers were the most common in each group (77% of the screening group and 78% of the usual care group).

The women in this study were part of the PLCO (Prostate, Lung, Colorectal and Ovarian) cancer screening trial. In all, 68,557 women aged 55-74 years were assigned to either annual screening (34,253 women) or usual care (34,304 women) in 1993-2001 and remained in the analysis. Women in the screening arm were offered annual CA 125 testing for 6 years and transvaginal ultrasound for 4 years. Those in the usual care arm were not offered the screening tests. The median follow-up was 12.4 years.

Women with a CA 125 level of 35 U/mL or greater were classified as abnormal. Transvaginal ultrasound was conducted using a 5-7.5 MHz transvaginal probe. Results were considered abnormal if the ovarian volume was greater than 10 cm³, if the cyst volume was greater than 10 cm³, if any solid area or papillary projection extending into the cavity of a cystic ovarian tumor of any size was present, or if any mixed (solid and cystic) component within a cystic ovarian tumor was present.

Both the women and their physicians were notified in writing about suspicious abnormalities found through screening. The women’s primary care physicians were responsible for managing the diagnostic process to assess abnormalities.

Among women in the screening arm, there were a greater number of false positives (3,285 false positives vs. 212 true positives). Of women who had a false positive test, one-third (1,080 women) underwent surgery for biopsy to evaluate positive test results. Of these, 163 (15%) women had 222 distinct major complications.

One of the authors, Jonathan D. Clapp, reported having a financial interest in Human Genome Sciences Inc. The other authors reported that they had no relevant financial relationships. The National Cancer Institute funded the PLCO cancer screening trial.

Kerri Wachter contributed to this article.

CHICAGO - Screening for ovarian cancer did not reduce the risk of dying from the disease for women with average risk, according to results of a multicenter screening study of nearly 80,000 women.

Screening nearly 40,000 post-menopausal women with transvaginal ultrasound for 4 years and CA-124 for 6 years did not decrease ovarian cancer mortality compared to nearly 40,000 control women. Further, there was evidence of harm in the 3,285 women with false positive results; 1080 women had surgery and 163 of them had 222 major complications, according to Dr. Saundra Buys, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, whose presentation of the data was given on June 4 at the annual meeting of the American Society of Clinical Oncology. The study appears in the June 8 issue of JAMA (2011;305:2295-303). 

Among women who underwent screening, 118 died of ovarian cancer, whereas 100 women who received usual care died as a result of the disease. The difference was not significant.

"It is possible that even an optimized program of annual screening may be insufficient to detect cancers early enough to reduce mortality. Evidence from modeling suggests that aggressive cancers progress rapidly through the early stages, limiting the ability to detect these cancers with yearly screening," Dr. Buys said.

More ovarian cancers were diagnosed in the screened women (212 vs. 176), although this difference was not significant. This suggests "that some of the additional cancers detected by screening were not clinically important and, if left undetected, may never have caused any symptoms or affected the women during their lifetimes," for example, with overdiagnosis, the researchers observed. Stage III and IV cancers were the most common in each group (77% of the screening group and 78% of the usual care group).

The women in this study were part of the PLCO (Prostate, Lung, Colorectal and Ovarian) cancer screening trial. In all, 68,557 women aged 55-74 years were assigned to either annual screening (34,253 women) or usual care (34,304 women) in 1993-2001 and remained in the analysis. Women in the screening arm were offered annual CA 125 testing for 6 years and transvaginal ultrasound for 4 years. Those in the usual care arm were not offered the screening tests. The median follow-up was 12.4 years.

Women with a CA 125 level of 35 U/mL or greater were classified as abnormal. Transvaginal ultrasound was conducted using a 5-7.5 MHz transvaginal probe. Results were considered abnormal if the ovarian volume was greater than 10 cm³, if the cyst volume was greater than 10 cm³, if any solid area or papillary projection extending into the cavity of a cystic ovarian tumor of any size was present, or if any mixed (solid and cystic) component within a cystic ovarian tumor was present.

Both the women and their physicians were notified in writing about suspicious abnormalities found through screening. The women’s primary care physicians were responsible for managing the diagnostic process to assess abnormalities.

Among women in the screening arm, there were a greater number of false positives (3,285 false positives vs. 212 true positives). Of women who had a false positive test, one-third (1,080 women) underwent surgery for biopsy to evaluate positive test results. Of these, 163 (15%) women had 222 distinct major complications.

One of the authors, Jonathan D. Clapp, reported having a financial interest in Human Genome Sciences Inc. The other authors reported that they had no relevant financial relationships. The National Cancer Institute funded the PLCO cancer screening trial.

Kerri Wachter contributed to this article.