The article by Vegunta et al. (1) provides guidance on anal cancer screening in high-risk women, a highly important topic. Anal squamous cell carcinoma (ASCC) incidence is increasing in women, and this trend is expected to continue. There are several recommendations for ASCC screening in high-risk men, namely HIV-positive men who have sex with men, but appropriate recommendations for women are lagging behind.
A recent comprehensive meta-analysis (2) has made an effort to compare all male and female risk groups on a unified scale of anal cancer incidence. It showed that the highest female risk groups for ASCC were, in descending order, women with >10-year history of organ transplantation (IR 50 per 100,000 py), women with vulvar cancer (IR 48 per 100,000 py) or vulva precancer (42 per 100,000 py), followed by HIV-positive women aged 45 years and older (30 per 100,000 py).
For transplanted females, years since transplantation (which is correlated with age) seems to be the most important risk stratifier (2), with studies also suggesting that the type of immunosuppressive drug (e.g., azathioprine) (3), might modulate anal cancer risk. When considering women with HPV-related genital cancer or precancer, women with vulvar cancer or precancer have a much higher ASCC risk than women with vaginal or cervical equivalents (2). In HIV-positive women, age is also an important risk stratifier, estimated at 30 per 100,000 above 45 years old, 17 at 30–44 years, and 5 at <30 years (2). Thus, age and time since transplant need to be taken into account in ASCC risk stratification and screening in high-risk women.
We particularly support Vegunta et al.'s (1) endorsement of human papillomavirus-16 (HPV-16) testing as a promising screening strategy, especially given that < 90% of female ASCCs are HPV-16-positive (4). Indeed, high correlation between concurrent cervical and anal HPV-16 (5) begs the research question of whether older women screening positive for cervical HPV-16 in cervical screening programs might also be at high enough ASCC risk to warrant screening.
Several societies have recommended a yearly anal cancer screening for HIV-positive men who have sex with men, but the risk in this population is much higher than in high-risk women, for whom, in addition, there are much less published data on anal screening algorithms. Importantly, Vegunta et al.'s (1) recommendations for algorithms are not accompanied by a grading of the strength and quality of the underlying evidence (e.g., GRADE system), which is crucial to making this process more transparent and uniform.
Certainly, recommendations for anal cancer screening are needed for high-risk women, but they also need to be supported by most up to date evidence of ASCC incidence and clearly graded. Even in the absence of evidence on performance of screening algorithms in women, at least we can base research and guidelines on a broad principle of similar management for similar ASCC risk, irrespective of sex.
CONFLICTS OF INTEREST
Guarantor of the article: Andreia Albuquerque, MD, PhD.
Specific author contributions: A.A. provided the concept and wrote the letter. P.V.B. revised the letter, and G.C. revised the letter and provided important intellectual content.
Financial support: None to report.
Potential competing interests: None to report. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization.
1. Vegunta S, Shah AA, Whited MH, et al. Screening women for anal cancers: Guidance for Health care professionals. Am J Gastroenterol 2021;116:509–16.
2. Clifford GM, Georges D, Shiels MS, et al. A meta-analysis of anal cancer incidence by risk group: Toward a unified anal cancer risk scale. Int J Cancer 2021;148:38–47.
3. Madeleine MM, Finch JL, Lynch CF, et al. HPV-related cancers after solid organ transplantation in the United States. Am J Transpl 2013;13:3202–9.
4. Lin C, Franceschi S, Clifford GM. Human papillomavirus types from infection to cancer in the anus, according to sex and HIV status: A systematic review and meta-analysis. Lancet Infect Dis 2018;18:198–206.
5. Lin C, Slama J, Gonzalez P, et al. Cervical determinants of anal HPV infection and high-grade anal lesions in women: A collaborative pooled analysis. Lancet Infect Dis 2019;19:880–91.