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COLLEGE PARK, MD. – A Food and Drug Administration advisory panel has unanimously supported expanding the approval of the cobas human papilloma virus test to include its use as a first-line primary cervical cancer screening test in women aged 25 years and older.
At a meeting on March 12, the FDA’s Microbiology Devices Advisory Committee voted 13-0 that the benefits of the cobas human papillomavirus (HPV) test, manufactured by Roche, outweighed the risks for use in women aged 25 years and older, for use as "a first-line primary cervical screening test to detect high-risk HPV, including genotyping for [HPV] 16 and 18." The proposed indication also states that women who test negative for high-risk HPV types "should be followed-up in accordance with the physician’s assessment of screening and medical history, other risk factors, and professional guidelines," and that women who test positive for HPV genotypes 16 and/or 18 "should be referred to colposcopy." Those who are positive for the other high-risk HPV types, but negative for 16/18 with this test, "should be evaluated by cervical cytology to determine the need for referral to colposcopy."
Despite some concerns about the age and the potential for confusion and off-label use of the test, panelists also voted 13-0 that there was reasonable assurance that the test was safe and effective for these proposed indications, with several panelists commenting on the task ahead for professional societies once the FDA approves the test for this use.
The cobas HPV test is an in vitro diagnostic test that detects 14 high-risk HPV types, including types 16 and 18, which are associated with about 70% of invasive cervical cancers. It was approved by the FDA in 2011 for screening women aged 21 years and older with abnormal cervical cytology results and for use adjunctively with normal cervical cytology in women aged 30 years and older to assess the presence or absence of high-risk HPV genotypes.
For approval, Roche submitted results of the ATHENA trial, a prospective study of 47,208 women in the United States, which was the basis of the 2011 approval, including 3-year follow-up data. The results show that HPV testing alone provides greater protection against CIN3 (cervical intraepithelial neoplasia grade 3) and invasive cervical cancer than does cytology alone, and that primary HPV testing provides a similar level of protection against CIN3 and invasive cervical cancer as cotesting with HPV testing and cytology, according to Roche.
Based on the proposed use, in women aged 25 years and older, the sensitivity of HPV testing for detecting CIN3 or higher was 58.26% vs. 42.63% for the comparator cytology alone, according to the FDA summary of the data. The positive predictive value for detecting CIN3 or greater among women referred to colposcopy with HPV testing was 12.25% vs. 6.47% for women referred to colposcopy with the cytology, a statistically significant difference. The risk of CIN3 or greater among women not referred to colposcopy with HPV testing was 0.42% vs. 0.59% among the women not referred to colposcopy with cytology. The false positive rate for CIN3 or greater was 4.09% among those in the HPV testing group, vs. 6.04% among those in the comparator.
Panelist Alan Waxman, professor in the department of obstetrics and gynecology, University of New Mexico, Albuquerque, commended the way the study was conducted, the results of which left the panel little choice on how to vote, and said that women will be "well served by having more choices." Clinicians will have different options for screening women, with potentially different intervals and triage trees, and the challenge will be for the professional societies "to put together data-driven, evidence-based algorithms," and then provide education for health care providers and patients, Dr. Waxman said.
"The balance of safety and effectiveness depends critically on the screening interval," added another panelist, Dr. L. Stewart Massad, professor of obstetrics and gynecology in the division of gynecologic oncology, Washington University, St. Louis. "This is a powerful test with a very strong negative predictive value, and the likelihood of disease will be substantially less than in the data presented today in women who are screened at too short an interval after an initial negative screen," which he said he hoped would be considered by professional societies in the development of guidelines.
About 1% of the women in the ATHENA study had been vaccinated against HPV, and panelists noted that as HPV vaccination increases, the effectiveness of screening would be lower because there will be less disease to detect. The oncologist on the panel, Dr. Joanna Cain, professor of obstetrics and gynecology at the University of Massachusetts, Worcester, said that patient registries could help understand how these proposals will need to modified over time as a result of HPV vaccination.
The FDA usually follows the recommendations of its advisory panels.
Advisory panel members have been cleared of potential conflicts related to the meeting topic. Occasionally, a panelist is given a waiver, but no waivers were given at this meeting.
COLLEGE PARK, MD. – A Food and Drug Administration advisory panel has unanimously supported expanding the approval of the cobas human papilloma virus test to include its use as a first-line primary cervical cancer screening test in women aged 25 years and older.
At a meeting on March 12, the FDA’s Microbiology Devices Advisory Committee voted 13-0 that the benefits of the cobas human papillomavirus (HPV) test, manufactured by Roche, outweighed the risks for use in women aged 25 years and older, for use as "a first-line primary cervical screening test to detect high-risk HPV, including genotyping for [HPV] 16 and 18." The proposed indication also states that women who test negative for high-risk HPV types "should be followed-up in accordance with the physician’s assessment of screening and medical history, other risk factors, and professional guidelines," and that women who test positive for HPV genotypes 16 and/or 18 "should be referred to colposcopy." Those who are positive for the other high-risk HPV types, but negative for 16/18 with this test, "should be evaluated by cervical cytology to determine the need for referral to colposcopy."
Despite some concerns about the age and the potential for confusion and off-label use of the test, panelists also voted 13-0 that there was reasonable assurance that the test was safe and effective for these proposed indications, with several panelists commenting on the task ahead for professional societies once the FDA approves the test for this use.
The cobas HPV test is an in vitro diagnostic test that detects 14 high-risk HPV types, including types 16 and 18, which are associated with about 70% of invasive cervical cancers. It was approved by the FDA in 2011 for screening women aged 21 years and older with abnormal cervical cytology results and for use adjunctively with normal cervical cytology in women aged 30 years and older to assess the presence or absence of high-risk HPV genotypes.
For approval, Roche submitted results of the ATHENA trial, a prospective study of 47,208 women in the United States, which was the basis of the 2011 approval, including 3-year follow-up data. The results show that HPV testing alone provides greater protection against CIN3 (cervical intraepithelial neoplasia grade 3) and invasive cervical cancer than does cytology alone, and that primary HPV testing provides a similar level of protection against CIN3 and invasive cervical cancer as cotesting with HPV testing and cytology, according to Roche.
Based on the proposed use, in women aged 25 years and older, the sensitivity of HPV testing for detecting CIN3 or higher was 58.26% vs. 42.63% for the comparator cytology alone, according to the FDA summary of the data. The positive predictive value for detecting CIN3 or greater among women referred to colposcopy with HPV testing was 12.25% vs. 6.47% for women referred to colposcopy with the cytology, a statistically significant difference. The risk of CIN3 or greater among women not referred to colposcopy with HPV testing was 0.42% vs. 0.59% among the women not referred to colposcopy with cytology. The false positive rate for CIN3 or greater was 4.09% among those in the HPV testing group, vs. 6.04% among those in the comparator.
Panelist Alan Waxman, professor in the department of obstetrics and gynecology, University of New Mexico, Albuquerque, commended the way the study was conducted, the results of which left the panel little choice on how to vote, and said that women will be "well served by having more choices." Clinicians will have different options for screening women, with potentially different intervals and triage trees, and the challenge will be for the professional societies "to put together data-driven, evidence-based algorithms," and then provide education for health care providers and patients, Dr. Waxman said.
"The balance of safety and effectiveness depends critically on the screening interval," added another panelist, Dr. L. Stewart Massad, professor of obstetrics and gynecology in the division of gynecologic oncology, Washington University, St. Louis. "This is a powerful test with a very strong negative predictive value, and the likelihood of disease will be substantially less than in the data presented today in women who are screened at too short an interval after an initial negative screen," which he said he hoped would be considered by professional societies in the development of guidelines.
About 1% of the women in the ATHENA study had been vaccinated against HPV, and panelists noted that as HPV vaccination increases, the effectiveness of screening would be lower because there will be less disease to detect. The oncologist on the panel, Dr. Joanna Cain, professor of obstetrics and gynecology at the University of Massachusetts, Worcester, said that patient registries could help understand how these proposals will need to modified over time as a result of HPV vaccination.
The FDA usually follows the recommendations of its advisory panels.
Advisory panel members have been cleared of potential conflicts related to the meeting topic. Occasionally, a panelist is given a waiver, but no waivers were given at this meeting.
COLLEGE PARK, MD. – A Food and Drug Administration advisory panel has unanimously supported expanding the approval of the cobas human papilloma virus test to include its use as a first-line primary cervical cancer screening test in women aged 25 years and older.
At a meeting on March 12, the FDA’s Microbiology Devices Advisory Committee voted 13-0 that the benefits of the cobas human papillomavirus (HPV) test, manufactured by Roche, outweighed the risks for use in women aged 25 years and older, for use as "a first-line primary cervical screening test to detect high-risk HPV, including genotyping for [HPV] 16 and 18." The proposed indication also states that women who test negative for high-risk HPV types "should be followed-up in accordance with the physician’s assessment of screening and medical history, other risk factors, and professional guidelines," and that women who test positive for HPV genotypes 16 and/or 18 "should be referred to colposcopy." Those who are positive for the other high-risk HPV types, but negative for 16/18 with this test, "should be evaluated by cervical cytology to determine the need for referral to colposcopy."
Despite some concerns about the age and the potential for confusion and off-label use of the test, panelists also voted 13-0 that there was reasonable assurance that the test was safe and effective for these proposed indications, with several panelists commenting on the task ahead for professional societies once the FDA approves the test for this use.
The cobas HPV test is an in vitro diagnostic test that detects 14 high-risk HPV types, including types 16 and 18, which are associated with about 70% of invasive cervical cancers. It was approved by the FDA in 2011 for screening women aged 21 years and older with abnormal cervical cytology results and for use adjunctively with normal cervical cytology in women aged 30 years and older to assess the presence or absence of high-risk HPV genotypes.
For approval, Roche submitted results of the ATHENA trial, a prospective study of 47,208 women in the United States, which was the basis of the 2011 approval, including 3-year follow-up data. The results show that HPV testing alone provides greater protection against CIN3 (cervical intraepithelial neoplasia grade 3) and invasive cervical cancer than does cytology alone, and that primary HPV testing provides a similar level of protection against CIN3 and invasive cervical cancer as cotesting with HPV testing and cytology, according to Roche.
Based on the proposed use, in women aged 25 years and older, the sensitivity of HPV testing for detecting CIN3 or higher was 58.26% vs. 42.63% for the comparator cytology alone, according to the FDA summary of the data. The positive predictive value for detecting CIN3 or greater among women referred to colposcopy with HPV testing was 12.25% vs. 6.47% for women referred to colposcopy with the cytology, a statistically significant difference. The risk of CIN3 or greater among women not referred to colposcopy with HPV testing was 0.42% vs. 0.59% among the women not referred to colposcopy with cytology. The false positive rate for CIN3 or greater was 4.09% among those in the HPV testing group, vs. 6.04% among those in the comparator.
Panelist Alan Waxman, professor in the department of obstetrics and gynecology, University of New Mexico, Albuquerque, commended the way the study was conducted, the results of which left the panel little choice on how to vote, and said that women will be "well served by having more choices." Clinicians will have different options for screening women, with potentially different intervals and triage trees, and the challenge will be for the professional societies "to put together data-driven, evidence-based algorithms," and then provide education for health care providers and patients, Dr. Waxman said.
"The balance of safety and effectiveness depends critically on the screening interval," added another panelist, Dr. L. Stewart Massad, professor of obstetrics and gynecology in the division of gynecologic oncology, Washington University, St. Louis. "This is a powerful test with a very strong negative predictive value, and the likelihood of disease will be substantially less than in the data presented today in women who are screened at too short an interval after an initial negative screen," which he said he hoped would be considered by professional societies in the development of guidelines.
About 1% of the women in the ATHENA study had been vaccinated against HPV, and panelists noted that as HPV vaccination increases, the effectiveness of screening would be lower because there will be less disease to detect. The oncologist on the panel, Dr. Joanna Cain, professor of obstetrics and gynecology at the University of Massachusetts, Worcester, said that patient registries could help understand how these proposals will need to modified over time as a result of HPV vaccination.
The FDA usually follows the recommendations of its advisory panels.
Advisory panel members have been cleared of potential conflicts related to the meeting topic. Occasionally, a panelist is given a waiver, but no waivers were given at this meeting.
AT AN FDA ADVISORY COMMITTEE MEETING
