Cervical Outcomes Similar With Immediate Cryotherapy and Standard Cytology in HIV+ Women
A high-risk HPV (hrHPV) test-and-treat strategy did no better than standard cytology-based screening in preventing cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with HIV, according to results of the 288-woman AIDS Clinical Trials Group (ACTG) A5282 study . But ACTG investigators believe their findings show the test-and-treat approach is feasible for lower-resource countries.
Standard cytology-based cervical cancer screening involves a 3-step process: (1) PAP smear, followed by (2) colposcopy and biopsy if the PAP smear is abnormal, and (3) treatment of cervical intraepithelial neoplasia grade 2 or 3 (the precursor to cervical cancer) with loop electrosurgical excision (LEEP) or other treatments. But that approach remains too resource-intensive in many regions affected by HIV. An alternative screening approach is to test for hrHPV and immediately perform cryotherapy in hrHPV-positive women--the test-and-treat strategy. In a large South African trial, women randomized to hrHPV test-and-treat had the lowest CIN2/3+ rate in follow-up, including a subgroup with HIV .
ACTG investigators hypothesized that HIV-positive women with hrHPV would have a lower probability of CIN2+ with immediate cryotherapy (test-and-treat) than with a cytology-based approach. Women randomized to immediate cryotherapy had two cervical biopsies followed by cryotherapy; women randomized to cytology-based screening had colposcopy and directed biopsies if cytology was abnormal, then LEEP if biopsy confirmed CIN2+ . The primary endpoint was CIN2+ (CIN2, CIN3, or invasive cancer) on cervical histology 26 weeks or more after randomization.
The trial enrolled nonpregnant HIV-positive women at least 18 years old with any CD4 count or HIV load. No one had a history of cervical, vulvar, or vaginal cancer, and no one had lesions that might be cancer. Women had cytology and samples stored for HPV testing every 6 months. Colposcopy and directed biopsies occurred at weeks 26, 78, and 130.
The 288 study participants (145 test-and-treat, 143 cytology) had a median age of 35 (interquartile range 31 to 41) and a median CD4 count of 501. Almost two thirds of women, 62%, had an undetectable HIV load. While 74% of women were black, 19% were Asian and 7% Hispanic. Women lived in Africa, India, Haiti, or Peru. While 237 women (82%) completed protocol-defined follow-up, 51 (18%) dropped out early.
Among 145 women randomized to test-and-treat, 143 successfully underwent cervical biopsies and cryotherapy. Thirteen of these 145 (9%) had no result, 93 (64%) had normal biopsies or CIN1, 38 (26%) had CIN2 or CIN3, and 1 (1%) had cervical cancer. Among 143 women in the cytology group, 92 (64%) had abnormal cytology, 85 (92%) of whom had colposcopy and biopsies. Of the 51 women with normal cytology, 22 (43%) had colposcopy and biopsies. Twenty-two women (15%) in the cytology group got diagnosed with CIN2/3, but only 12 of those 22 had LEEP.
Development of CIN2+ did not differ significantly between the test-and-treat group (24.9%) and the cytology group (26.5%) (difference 1.6%, 95% confidence interval -9.8% to 13.1%). Proportions of women with abnormal cervical cytology were similar in the test-and-treat arm and the cytology arm at week 0 (72% and 63%), week 26 (65% and 65%), week 78 (59% and 61%), and week 130 (43% and 49%). Rates of hrHPV at week 26 were 61% in the test-and-treat arm and 70% in the cytology arm.
The ACTG team concluded that the hrHPV test-and-treat strategy does not improve CIN outcomes 2.5 years after therapy when compared with single-round cytology-based screening. They suggested the results may reflect worse-than-expected response to cryotherapy in these women. But the investigators proposed that the test-and-treat approach to screening "is feasible for lower resource settings and leads to similar outcomes as the resource-intensive cytology-based approach."
1. Wilkin T, Matining R, Sahasrabuddhe V, et al. ACTG A5282: HPV test & treat vs. cytology-based cervical cancer prevention in HIV+ women. 25th Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2018. Boston. Abstract 134.
2. Kuhn L, Wang C, Tsai WY, Wright TC, Denny L. Efficacy of human papillomavirus-based screen-and-treat for cervical cancer prevention among HIV-infected women. AIDS. 2010;24:2553-2561.
3. ClinicalTrials.gov. HPV test-and-treat-strategy versus cytology-based strategy for prevention of CIN2+ in HIV-infected women. ClinicalTrial.gov identifier NCT01315353.