TY - JOUR
T1 - Screening strategies for the detection of anal high-grade squamous intraepithelial lesions in women living with HIV
AU - Chiao, Elizabeth Y.
AU - Lensing, Shelly Y.
AU - Wiley, Dorothy J.
AU - Deshmukh, Ashish A.
AU - Lee, Jeannette
AU - Darragh, Teresa M.
AU - Einstein, Mark H.
AU - Jay, Naomi
AU - Berry-Lawhorn, John Michael
AU - Palefsky, Joel M.
AU - Wilkin, Timothy
AU - Barroso, Luis F.
AU - Cranston, Ross D.
AU - Levine, Rebecca
AU - Guiot, Humberto M.
AU - French, Audrey L.
AU - Citron, Deborah
AU - Rezaei, Masoumeh Katayoon
AU - Goldstone, Stephen E.
AU - Stier, Elizabeth A.
N1 - Funding Information:
This work was supported by the National Cancer Institute at the National Institutes of Health, CA163103 to E.C. and E.A.S. (PI: E.C.) and UM1CA121947 to E.C., S.Y.L., E.A.S., and AIDS Malignancy Consortium sites (PI: Dr Ronald Mitsuyasu). Qiagen, Hologic, and HPV-Aptima provided in-kind contributions for HPV testing.
Funding Information:
The submitted COIs detail the various grants, fees as well as nonfinancial support that any of the authors have received during the course the study. A brief overview of the details captured in the COIs is presented here. D.C., M.K.R., L.F.B., H.M.G., N.J., S.Y.L., R.L., A.L.F., and E.C. do not have anything to disclose other than funding from the NIH, and don’t report any conflict of interest. S.E.G. received personal fees from Merck and Co, grants and other form of payments Medtronic Inc, grants from Antiva, Inovio, and other support from THD America. T.M.D. reports nonfinancial support from Hologic and personal fees from Roche, BD, Antiva, and TheVax. M.H.E. has advised or participated in educational speaking activities but does not receive an honorarium from any companies. In specific cases, his employers have received payment for his time spent for these activities from Papivax, Cynvec, Altum Pharma, Photocure, Becton Dickenson, and PDS Biotechnologies. Rutgers has received grant funding for research-related costs of clinical trials that M.H.E. has been the overall or local PI within the past 12 months from J&J, Pfizer, AstraZeneca, Advaxis, and Inovio. M.H.E. also reports other support from Photocure, Papivax, Cynvec, PDS, Altum Pharma, and Becton Dickinson, outside the submitted work. E.A.S. reports nonfinancial support from Qiagen and Hologic, Inc. J.M.B.-L. reports personal fees from ANTIVA and A.A.D. reports personal fees from Merck Inc. J.M.P. received grants and nonfinancial support from Merck and Co. He also received grants, personal fees, and other support from Vir Biotechnologies, Ubiome, and Antiva Biosciences. He received personal fees from Janssen Pharmaceuticals, Novan, Vaccitech, and nonfinancial support from Virion Therapeutics. D.J.W. reports grants from National Cancer Institute, during the conduct of the study and is a Merck & Co., Inc. [Merck, Sharp & Dohme (MSD)]: Speakers Bureau member. T.W. reports grants and personal fees from GlaxoSMithKline/ ViiV Healthcare, outside the submitted work.
Publisher Copyright:
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Objective: HIV-infected women (WLHIV) have more than 10-fold higher risk for squamous cell cancer of the anus. Experts suggest cytology-based strategies developed for cervical cancer screening may prevent anal cancer by detecting anal cytologic or histological high-grade squamous intraepithelial lesion (hHSIL) for treatment. Currently, there is no consensus on anal-hHSIL screening strategies for WLHIV. Design: Between 2014 and 2016, 276 WLHIV were recruited at 12 US AIDS Malignancy Consortium clinical trials sites to evaluate hHSIL prevalence and (test) screening strategies. Methods: Participants completed detailed questionnaire, underwent anal assessments including high-risk human papillomavirus (hrHPV) testing using hrHPV-Hybrid Capture 2 (HC2) and hrHPV-APTIMA, anal cytology, and concurrent high-resolution anoscopy. Screening test characteristics for predicting hHSIL validated by central review of histologic diagnosis were estimated sensitivity, specificity, positive predictive value, and false-omission rate. Paired analyses compared sensitivity and specificity for hrHPV single tests to anal cytology alone. Results: 83% (229/276) of enrolled WLHIV had complete anal assessment data and were included in this analysis. Mean age was 50, 62% black and 60 (26%) had hHSIL. Anal cyotology (>atypical squamous cells of undetermined significance), hrHPV-HC2, and hrHPV-APTIMA sensitivity estimates were similarly high (83, 77, and 75%, respectively, P values > 0.2). Specificity was higher for both hrHPV-APTIMA and hrHPV-HC2 compared with anal cytology (67 vs. 50%, P < 0.001) and (61 vs. 50%, P ¼ 0.020), respectively. Conclusion: Anal hrHPV testing demonstrated similar sensitivity for anal cytology (>atypical squamous cells of undetermined significance) to predict anal hHSIL. Among tests with similar sensitivity, the specificity was significantly higher for hrHPV-APTIMA and hrHPV-HC2. Thus, anal hrHPV testing may be an important alternative strategy to anal cytology for anal hHSIL screening among WLHIV.
AB - Objective: HIV-infected women (WLHIV) have more than 10-fold higher risk for squamous cell cancer of the anus. Experts suggest cytology-based strategies developed for cervical cancer screening may prevent anal cancer by detecting anal cytologic or histological high-grade squamous intraepithelial lesion (hHSIL) for treatment. Currently, there is no consensus on anal-hHSIL screening strategies for WLHIV. Design: Between 2014 and 2016, 276 WLHIV were recruited at 12 US AIDS Malignancy Consortium clinical trials sites to evaluate hHSIL prevalence and (test) screening strategies. Methods: Participants completed detailed questionnaire, underwent anal assessments including high-risk human papillomavirus (hrHPV) testing using hrHPV-Hybrid Capture 2 (HC2) and hrHPV-APTIMA, anal cytology, and concurrent high-resolution anoscopy. Screening test characteristics for predicting hHSIL validated by central review of histologic diagnosis were estimated sensitivity, specificity, positive predictive value, and false-omission rate. Paired analyses compared sensitivity and specificity for hrHPV single tests to anal cytology alone. Results: 83% (229/276) of enrolled WLHIV had complete anal assessment data and were included in this analysis. Mean age was 50, 62% black and 60 (26%) had hHSIL. Anal cyotology (>atypical squamous cells of undetermined significance), hrHPV-HC2, and hrHPV-APTIMA sensitivity estimates were similarly high (83, 77, and 75%, respectively, P values > 0.2). Specificity was higher for both hrHPV-APTIMA and hrHPV-HC2 compared with anal cytology (67 vs. 50%, P < 0.001) and (61 vs. 50%, P ¼ 0.020), respectively. Conclusion: Anal hrHPV testing demonstrated similar sensitivity for anal cytology (>atypical squamous cells of undetermined significance) to predict anal hHSIL. Among tests with similar sensitivity, the specificity was significantly higher for hrHPV-APTIMA and hrHPV-HC2. Thus, anal hrHPV testing may be an important alternative strategy to anal cytology for anal hHSIL screening among WLHIV.
KW - Anal cytology
KW - Anal dysplasia
KW - High-risk human papillomavirus test
KW - Operating characteristics
KW - Screening
KW - Women living with HIV
UR - http://www.scopus.com/inward/record.url?scp=85096347530&partnerID=8YFLogxK
U2 - 10.1097/QAD.0000000000002694
DO - 10.1097/QAD.0000000000002694
M3 - Article
C2 - 32947592
AN - SCOPUS:85096347530
SN - 0269-9370
VL - 34
SP - 2249
EP - 2258
JO - AIDS
JF - AIDS
IS - 15
ER -