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Original Investigation
January 13, 2021

The Risk of Anal Carcinoma After Anogenital Warts in Adults Living With HIV

Author Affiliations
  • 1George Washington University School of Medicine and Health Sciences, Washington, DC
  • 2Now with Transitional Year Residency, Riverside Community Hospital, University of California, Riverside
  • 3Milken Institute School of Public Health, Department of Epidemiology, George Washington University, Washington, DC
  • 4Whitman-Walker Health, Washington, DC
JAMA Dermatol. 2021;157(3):283-289. doi:10.1001/jamadermatol.2020.5252
Key Points

Question  What is the risk of developing anal carcinoma after anal or genital warts in adults living with HIV?

Findings  In this cohort study including 6515 adults living with HIV, 17 of 383 individuals with anogenital warts (4.4%) developed anal carcinoma vs 17 of 6132 individuals without warts of the anogenital region (0.3%). After adjusting for covariates, the odds of developing anal carcinoma were 12.79 times higher in individuals with a history of anogenital warts compared with individuals without a history of anogenital warts.

Meaning  These findings suggest that persons living with HIV who have anogenital warts should be counseled that they have an increased risk of developing anal carcinoma.

Abstract

Importance  In the US, incidence of and mortality due to anal carcinoma are rising faster than for most other cancers. Identifying populations who have a higher risk of developing anal cancers is critical to target preventive interventions.

Objective  To assess the risk of developing anal carcinoma in adults living with HIV who have a history of anogenital warts.

Design, Setting, and Participants  This longitudinal cohort study included adults living with HIV from 14 clinics in Washington, DC, and at least 18 months of follow-up. Data were collected from January 1, 2011, to March 31, 2017, and analyzed from June 1, 2019, to October 31, 2020.

Exposures  Development of warts in the anal or genital region identified by diagnosis codes.

Main Outcomes and Measures  Individuals with anal carcinoma were identified by diagnosis codes or anal biopsy results.

Results  A total of 6515 participants were enrolled (4720 male [72.4%] at birth; mean [SD] age, 49.9 [12.7] years), and 383 (5.9%) developed anogenital warts during the study period. Patients who were diagnosed with anogenital warts were more likely to subsequently develop anal carcinoma (17 of 383 [4.4%]) compared with participants without a history of anogenital warts (17 of 6132 [0.3%]) (P < .001). After adjusting for covariates, the odds of developing anal carcinoma were 12.79 (95% CI, 6.19-26.45; P < .001) times higher in individuals with a history of anogenital warts compared with individuals without a history of anogenital warts.

Conclusions and Relevance  These findings suggest that adults living with HIV who have a history of anogenital warts have a substantially increased risk of developing anal carcinoma. Clinicians should counsel individuals living with HIV who have anogenital warts on this risk.

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    2 Comments for this article
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    Risk of anal carcinoma in HIV-positive adults with anogenital warts
    Tomoyuki Kawada, MD | Nippon Medical School
    Arnold et al. evaluated the risk of developing anal carcinoma in adults living with HIV (1). The adjusted odds ratio (95% confidence interval) of HIV-positive individuals with a history of anogenital warts for developing anal carcinoma was 12.79 (6.19-26.45). Anogenital warts are generally considered as benign lesions caused by low-risk human papillomavirus (HPV)-types, and I have two comments about their study.

    First, I understand that anogenital dysplasia is recognized as a cancer precursor associated with high-risk HPV-types. Kreuter et al. reported that anogenital warts in HIV-positive individuals, who have sex with men, also presented the increased risk of high-grade
    dysplasia or invasive squamous cell carcinoma, and recommended for excluding cancer precursors by histopathological approach (2). This report presented that even anogenital warts also contributed to developing anal carcinoma in adults living with HIV. Histopathological characteristics of anogenital warts should be included in multivariate analysis for calculating odds ratio.

    Second, Werner et al. conducted a meta-analysis of clinical trials regarding the health risk of anogenital warts or intraepithelial neoplasia in immunocompromised and HIV-positive patients (3). Unfortunately, insufficient information could be retrieved to specify the risk of anogenital warts and other HPV-associated anogenital lesions in the HIV-positive patients. Anyway, risk assessment of carcinoma in HIV-positive adults with anogenital warts should be conducted comprehensively.


    References
    1. Arnold JD, Byrne ME, Monroe AK, et al. The risk of anal carcinoma after anogenital warts in adults living with HIV. JAMA Dermatol. 2021 Jan 13. doi: 10.1001/jamadermatol.2020.5252
    2. Kreuter A, Siorokos C, Oellig F, et al. High-grade dysplasia in anogenital warts of HIV-positive men. JAMA Dermatol 2016;152(11):1225-1230.
    3. Werner RN, Westfechtel L, Dressler C, et al. Anogenital warts and other HPV-associated anogenital lesions in the HIV-positive patient: a systematic review and meta-analysis of the efficacy and safety of interventions assessed in controlled clinical trials. Sex Transm Infect 2017;93(8):543-550.
    CONFLICT OF INTEREST: None Reported
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    HPV related anal cancer
    Daniel Krell, M.D. | Retired PCP
    I don’t understand the study’s implication — by omission — that HPV-related cancer stops at the anus. Yes, this is in a dermatology journal, but I see this omission in too many other articles in other specialties to ignore it. Over recent years, there has been progressive concern about the increase of colorectal cancers, especially involving younger patients, without specific association with HIV infection. Various causes have been postulated but these articles almost never address the likelihood that HPV infection and anal intercourse (heterosexual and homosexual) are etiologic, in some/many(?) cases. There is no mention of relevant histories in these cases: receptive anal intercourse, age of onset of sexual activity, number of partners, anogenital warts, other HPV-related cancers, etc., that could shed light on this issue. This, despite the increased recognition and publicity of other HPV-related cancers (e.g., oropharyngeal) and recommendations supporting more widespread HPV vaccination.

    There has been recognition of these relationships, for years. I am concerned, however, that there is some silo effect that is hampering important, more widespread recognition and discussion of the HPV connection, and related recommendations for vaccination.



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    CONFLICT OF INTEREST: None Reported
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