Comparing Anal Cancer Screening Algorithms Using Cytology and Human Papillomavirus DNA Testing in 3 High-Risk Populations

Michael M. Gaisa, Keith M. Sigel, Ashish A. Deshmukh, Volha Lenskaya, Courtney A. Chan, Richard Silvera, John Winters, Yuxin Liu

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Background: Screening strategies for high-risk human papillomavirus (hrHPV)-associated anal cancer are evolving. Herein, we compare anal cytology to hrHPV DNA testing and 2 novel cytology/hrHPV cotesting algorithms among 3 high-risk populations. Methods: Anal cytology, hrHPV DNA testing, and high-resolution anoscopy (HRA)-guided biopsy results were analyzed from 1837 participants (1504 HIV-infected men who have sex with men (MSM), 155 HIV-uninfected MSM, and 178 HIV-infected women). Performance to detect histological high-grade squamous intraepithelial lesions (HSIL)/cancer was compared between 4 strategies with distinct HRA referral thresholds: cytology (atypical squamous cells of undetermined significance, ASCUS); hrHPV testing (any hrHPV positive); algorithm A (benign cytology/HPV16/18 positive or ASCUS/hrHPV positive); and algorithm B (benign or ASCUS/hrHPV positive). Results: Histological HSIL/cancer was detected in 756 (41%) participants. Cytology had the lowest sensitivity (0.76-0.89) but highest specificity (0.33-0.36) overall and for each subgroup. Algorithm B was the most sensitive strategy overall (0.97) and for MSM (HIV-infected 0.97; HIV-uninfected 1.00). For women, hrHPV testing and both algorithms yielded higher sensitivity than cytology (0.96, 0.98, and 0.96). Specificity was low for all strategies/subgroups (range, 0.16-0.36). Conclusions: Screening algorithms that incorporate cytology and hrHPV testing significantly increased sensitivity but decreased specificity to detect anal precancer/cancer among high-risk populations.

Original languageEnglish
Pages (from-to)881-888
Number of pages8
JournalJournal of Infectious Diseases
Issue number5
StatePublished - 1 Sep 2021


  • HPV DNA testing
  • anal cancer screening
  • high-grade squamous intraepithelial lesion
  • human immunodeficiency virus
  • human papillomavirus


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