ACOG Recommends Primary HPV Screening as Alternative to Cytology in Those 25 Years and Older
New guidelines stated that screening with an FDA-approved primary HPV test could substitute cytology-based cervical cancer screening methods.
Color January teal, for Cervical Cancer Awareness Month, and mark 2016 as the turning point in eradicating the disease, nearly 100% of which is caused by the human papillomavirus (HPV).1
Widespread screening has decreased cervical cancer incidence by more than 50% during the past 30 years, to an estimated 12 900 new cases and 4100 deaths in 2015.2
Now, a confluence of events has set the stage for ensuring cervical cancer prevalence continues to decline: the U.S. Food and Drug Administration (FDA) approved both a nanovalent HPV vaccine and the first test for primary, stand-alone cervical cancer screening in 2014,3,4 and this month the American College of Obstetricians and Gynecologists (ACOG) issued a new cervical cancer screening and prevention Practice Bulletin that stated screening with “the FDA-approved primary HPV screening test can be considered as a alternative to current cytology-based cervical cancer screening methods” in women 25 years and older.5
Screening women 25 to 29 years remains controversial, however, due in part to concern about the potential harms of beginning screening at 25 years, such as greater detection of cervical intraepithelial neoplasia (CIN) grade 3, triggering repeat colposcopies.
The ACOG recommendation is “Level B”; “Level A” states that cotesting with cytology and HPV testing every 5 years is “preferred” for women 30 to 65 years, while “cotesting should not be performed in women younger than 30 years.”
The “Level B” recommendation aligns with the 2015 publication of Society for Gynecologic Oncology and American Society for Colposcopy and Cervical Pathology interim clinical guidance on primary high-risk HPV testing.6
To provide this guidance, a panel of 13 experts convened to address an FDA application for a “marketed HPV test to be labeled for the additional indication of primary cervical cancer screening.” The registration study supporting the cobas HPV test label change was ATHENA—Addressing THE Need for Advanced HPV diagnostics—which was conducted among women 25 years or older attending routine cervical screening in 61 clinical centers in 23 US states. A total of 47 208 women were enrolled in ATHENA, 41 955 of whom met eligibility criteria.7
Of the 40 901 women (97%) who had valid cobas HPV and liquid-based cytology test results available, 4275 (10%) tested cobas HPV-positive and 2617 (6%) had abnormal cytology; 431 were diagnosed with CIN2 or worse and 274 with CIN3 or worse.
“In women who had colposcopy, the cobas HPV test was more sensitive than liquid-based cytology for detection of CIN3 or worse,” the study authors wrote in Lancet Oncology in 2011. Cobas, a qualitative multiplex assay, provides specific genotyping for HPV type 16 and 18 and concurrently detects 12 other high-risk HPV types in a pooled result, according to the manufacturer, Roche Molecular Systems.8
Catherine M. Behrens, MD, PhD, an obstetrician/gynecologist and ATHENA investigator, told Cancer Therapy Advisor that more than half the women in the 25 to 29 age group with CIN3+ on the cobas HPV test were found to have normal cytology, meaning they would not be due to be screened again for another 3 years.
Some would argue that because cervical cancer is an indolent disease, progression to cancer among this age group would be uncommon. Median age at diagnosis is 49 years, and is most frequently diagnosed among women 35 to 44 years.9
Yet, cervical cancer is “an imminently preventable disease,” said Dr Behrens, an independent consultant for research trials such as ATHENA. “Prevention starts with the vaccine and moves on to screening as women get older, and if we have a significant uptake of the vaccine, the next generation will require much less screening.”
Gardasil-9 is indicated in girls and young women between 9 and 25 years old. The 9-valent recombinant vaccine prevents cervical, vulvar, vaginal, and anal cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58; condyloma acuminata caused by HPV types 6 and 11; and precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, including CIN grade 2/3 and cervical adenocarcinoma in situ.10
Although a significant decline in number of cases of cervical cancer is not anticipated to occur until 2 decades following vaccination, Australia reported a decrease in high-grade cervical abnormalities within 3 years of implementing a nationally funded population-based program.11
Clinician attitude and recommendation are 2 of the most important determinants of immunization status among adolescents. Parents cite myriad factors against vaccinating their daughters—and sons—against HPV, including fear of promoting sexual activity.
The tools are available to prevent cervical cancer. What's needed now is widespread use of HPV vaccines and ensuring women who are unscreened or under-screened for cervical cancer are informed about the benefits and risks of primary HPV testing.
- Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin. 2012;62(3):147-172.
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2012;65(1):5-29.
- FDA approves Gardasil 9 for prevention of certain cancers caused by five additional types of HPV [news release]. U.S. Food and Drug Administration; December 10, 2014. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm426485.htm. Accessed December 28, 2015.
- FDA approves first human papillomavirus test for primary cervical cancer screening [news release]. U.S. Food and Drug Administration; April 24, 2014. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm394773.htm. Accessed December 28, 2015.
- Cervical cancer screening and prevention. Practice Bulletin No. 157. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2016;127(1):e1-20.
- Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: Interim clinical guidance. Gynecol Oncol. 2015;136(2):178-182.
- Castle PE, Stoler MH, Wright TC Jr, et al. Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study. Lancet Oncol. 2011;12(9):880-890.
- Roche Molecular Diagnostics. Cobas® HPV Test. http://molecular.roche.com/assays/Pages/cobasHPVTest.aspx. Accessed December 28, 2015.
- National Cancer Institute. Surveillance, Epidemiology, and End Results Program. SEER Stat Fact Sheets: Cervix Uteri Cancer. http://seer.cancer.gov/statfacts/html/cervix.html. Accessed December 28, 2015.
- Merck & Co., Inc. Gardasil ® 9. Prescribing information. https://www.merck.com/product/usa/pi_circulars/g/gardasil_9/gardasil_9_pi.pdf. Accessed December 28, 2015.
- Brotherton JML, Fridman M, May CL, et al. Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study. Lancet. 2011;377(26):2085-2092.