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Clinical Trial
. 2022 Oct 12;75(8):1280-1288.
doi: 10.1093/cid/ciac213.

A Randomized Clinical Trial of Human Papillomavirus Test-and-Treat as Compared to Cytology-Based Screening for Prevention of Cervical Cancer Among Women With Human Immunodeficiency Virus: AIDS Clinical Trials Group Protocol A5282

Timothy Wilkin  1 , Huichao Chen  2 , Vikrant Sahasrabuddhe  3 , Roy Matining  2 , Rosie Mngqibisa  4 , Lameck Chinula  5 , Yamikani Mbilizi  6 , Tsitsi Magure  7 , Ayotunde E Omoz-Oarhe  8 , Mohammed Rassool  9 , Cynthia Riviere  10 , Rhamesh Bhosale  11 , Sheela Godbole  12 , Reena Naranjo  13 , Robert Coombs  14 , Pamela Michelow  15 , Catherine Godfrey  16 , Cynthia Firnhaber  17
Affiliations
Clinical Trial

A Randomized Clinical Trial of Human Papillomavirus Test-and-Treat as Compared to Cytology-Based Screening for Prevention of Cervical Cancer Among Women With Human Immunodeficiency Virus: AIDS Clinical Trials Group Protocol A5282

Timothy Wilkin et al. Clin Infect Dis. .

Abstract

Background: Cytology-based cervical cancer screening followed by confirmation and treatment of biopsy-proven high-grade squamous intraepithelial lesions (bHSIL) is difficult to implement in resource-constrained settings. We hypothesized that high-risk human papillomavirus (hrHPV) testing followed by immediate cryotherapy of women with hrHPV (HPV screen-and-treat) may improve outcomes.

Methods: Randomized, open-label, phase 2, multinational clinical trial enrolling women with human immunodeficiency virus (HIV) age 18 or older with cervical hrHPV and having no cervical lesions or lesions appropriate for cryotherapy. Women were randomized to immediate cryotherapy (Arm A) or cytology-based screening (Arm B). For Arm A, cervical biopsies were obtained followed by cervical cryotherapy, and in Arm B, women with abnormal cytology underwent colposcopy followed by loop electroexcision procedure (LEEP) if bHSIL was detected. Women were followed through 30 months. The primary outcome was time to bHSIL detected from Month 6 through study completion.

Results: In total, 288 women (145 in Arm A, 143 in Arm B) were randomized: median age 35 years, 84% on antiretroviral therapy, median CD4 501 cells/mm3. In Arm A, 39 (27%) of women had bHSIL at entry, and in Arm B, 88 (62%) had abnormal cytology, 22 (15%) were diagnosed with bHSIL, 12 (8%) underwent LEEP. In follow-up, 30 (21%) and 31 (22%) developed bHSIL; time to bHSIL was similar between arms (P=.94). The prevalence of hrHPV at Month 6 was similar between arms (61% and 70%, P=.13).

Conclusions: HPV test-and-treat was not associated with improved bHSIL outcomes as compared to cytology-based screening. More effective treatment options are required to improve outcomes from screen-and-treat programs.

Clinical trials registration: NCT01315363.

Keywords: HIV; HPV; cervical cancer; cytology; women.

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Conflict of interest statement

Potential conflicts of interest. T. J. W. has received grant funding paid to Weill Cornell Medicine from Bristol Myers-Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, and Merck Sciences, and has received honoraria from GlaxoSmithKline/ViiV Healthcare and Merck Sciences and reports consulting fees from Merck Sciences. H. C. reports support for attending meetings and/or travel from the NIH paid to the institution. S. G. reports support for the present manuscript from AIDS Clinical Trials Group, DAIDS NIH USA, for trial conduct. R. N. reports support for the present manuscript from AIDS Clinical Trials Group, funded by the Division of AIDS within the NIAID, payments made to the institution to support the ACTG Network’s Coordinating Center at Social & Scientific Systems, Inc. R. W. C. reports grants or contracts UM1 AI068636 and UM1 AI106701 outside of the submitted work. C. F. reports MERCK travel grant for airline tickets/hotel for CROI 2019 to present HPV/Cervical Dysplasia investigator driven study made to airline/hotel. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Consort diagram. Abbreviations: bhSIL, biopsy-proven high-grade squamous intraepithelial lesions; HPV, human papillomavirus; hr-HPV, high-risk human papillomavirus.
Figure 2.
Figure 2.
Kaplan-Meier Curve for time to high-grade squamous intraepithelial lesion on biopsy. Abbreviations: bHSIL, biopsy-proven high-grade squamous intraepithelial lesion; CI, confidence interval.
Figure 3.
Figure 3.
Kaplan-Meier Curve for time to bHSIL according to baseline cytology results. Abbreviations: bHSIL, biopsy-proven high-grade squamous intraepithelial lesion; CI, confidence interval.
Figure 4.
Figure 4.
Kaplan-Meier Curve for time to bHSIL according to baseline histology results. Abbreviations: bHSIL, biopsy-proven high-grade squamous intraepithelial lesion; CI, confidence interval.
See this image and copyright information in PMC

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