Primary human papillomavirus (HPV) testing may soon replace cytology for cervical cancer screening in average-risk women

EBM Focus - Volume 13, Issue 31

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Reference: JAMA 2018 Aug 21;320(7):674 (level 1 [likely reliable] evidence)

Interim guidance from the American College of Obstetricians and Gynecologists (Obstet Gynecol. 2016 Oct;128(4):e111-30) that primary high-risk HPV screening be considered as an alternative to cytology-based cervical cancer screening reflects emerging data suggesting HPV screening may be as good or better than cytology-based testing for detection of cervical intraepithelial neoplasia (CIN). The USPSTF recommends the Pap test for women aged 21 to 29 years and three strategies to screen women aged 30 to 65 years: Pap test, HPV test, or both in combination (cotesting).

In the HPV FOr CervicAL cancer (FOCAL) Trial (JAMA. 2018 Jul 3;320(1):43-52), investigators randomized 19,009 women of average risk aged 25-65 years to screening with liquid-based cytology alone vs primary HPV testing and compared rates of CIN grade 3 or worse (primary outcome), CIN grade 2 or worse, and colposcopy rates at 48 months (secondary outcomes). Women with negative baseline cytology testing were followed up at 24 and 48 months and those negative primary HPV testing were followed up at 48 months. Women with abnormal cytology or HPV testing at any time during the trial received additional evaluation and treatment and those with lesions less than CIN 2 were invited for final screening at 48 months. At 48 months, all women had both cytology and HPV testing performed.

In analysis of all women at trial conclusion, women who underwent primary HPV testing had lower rates of CIN grade 3 or worse (risk ratio [RR] 0.42, CI 0.25 - 0.69) and lower rates of CIN grade 2 or worse (RR 0.47, CI 0.34 - 0.67). Similar results were found in subgroup analyses of all women with negative baseline screening. Interestingly, higher rates of colposcopy and biopsy were seen earlier on in the trial period for women receiving HPV testing (absolute difference 26.2, CI 20.4 - 32.1), but overall rates of colposcopy were lower for this group at 48 months (absolute difference -21.3, CI -28.3 to -14.8); cumulative colposcopy referral rates were similar between both groups at the end of the trial period (absolute difference 4.7, CI -4.0 - 13.4). Certainly, long-term follow up is needed to verify the diagnostic aptitude as well as cost-effectiveness of primary HPV screening.
Focus point: As reflected in the recent guideline update for cervical cancer screening by the USPSTF, accumulating yet still early data point to HPV testing a as possibly superior method of screening compared to cytology alone.

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