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Testing for Human Papillomavirus Strains 16 and 18 Helps Predict the Presence of Anal High-Grade Squamous Intraepithelial Lesions

Sambursky, Jacob A., B.S.1; Terlizzi, Joseph P., M.D.2; Goldstone, Stephen E., M.D.2

doi: 10.1097/DCR.0000000000001143
Original Contributions: Colorectal Cancer
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BACKGROUND: More than 90% of anal cancers are caused by human papillomavirus, and human papillomavirus strains 16 and 18 are the most oncogenic. Anal high-grade squamous intraepithelial lesions are cancer precursors. Treating these high-grade intraepithelial lesions likely reduces the risk of cancer, but cytology is an imperfect screening test.

OBJECTIVE: The purpose of this study was to determine whether human papillomavirus 16 and/or 18 testing better predicts the presence of high-grade squamous intraepithelial lesions.

DESIGN: In this retrospective study, 894 consecutive patients underwent anal dysplasia screening with digital anorectal examination, anal cytology, high-risk human papillomavirus testing, and high-resolution anoscopy with biopsy. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of each test and for a novel screening protocol. The absolute and relative risk of high-grade squamous intraepithelial lesions for all of the cytology/human papillomavirus combinations were also calculated.

SETTINGS: The study was conducted at a single practice specializing in anal dysplasia.

PATIENTS: Ninety-two percent of participants were men who have sex with men. Forty-four percent were HIV-positive individuals who were well controlled on antiretroviral therapy. The median age was 50 years.

MAIN OUTCOME MEASURES: The presence of high-grade squamous intraepithelial lesions as a function of human papillomavirus and the cytology results were measured.

RESULTS: High-risk human papillomavirus testing alone demonstrated better sensitivity (96% vs 89%; p = 0.03) and negative predictive value (99% vs 96%; p = 0.008) over cytology. Human papillomavirus 16/18 testing increased specificity (48% to 71%; p < 0.0001) and positive predictive value (24% to 37%; p = 0.003) over testing for all of the high-risk strains. For each cytology category, high-grade squamous intraepithelial lesions were more prevalent when human papillomavirus 16/18 was detected. Benign cytology with 16/18 had a 31-fold increased risk of high-grade squamous intraepithelial lesions.

LIMITATIONS: This study was conducted in a single private practice specializing in anal dysplasia screening with a mostly male population, and results might not be generalizable.

CONCLUSIONS: Testing of high-risk human papillomavirus strains 16/18 improves specificity and positive predictive value over cytology for anal dysplasia screening. Patients testing positive for strains 16/18 are at a high risk for high-grade squamous intraepithelial lesions and should undergo high-resolution anoscopy regardless of the cytology result. See Video Abstract at

1 Department of Medical Education, College of Medicine, University of Central Florida, Orlando, Florida

2 Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York

Funding/Support: Stephen E. Goldstone, M.D. received funding from Medtronic, Inc., Inovio; Antiva.

Financial Disclosure: Stephen E. Goldstone, M.D. is a consultant for Merck & Co., Medtronic, and THD America.

Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, WA, June 10 to 14, 2017.

Jacob A. Sambursky and Joseph P. Terlizzi contributed equally to this article.

Correspondence: Stephen E. Goldstone, M.D., 420 W 23rd Street, Suite PB1F, New York, NY 10011. E-mail:

© 2018 The American Society of Colon and Rectal Surgeons