Risk stratification and anal cancer screening in immunocompetent women with genital HPV: Value of multicentric HSIL and performance of HPV-based screening

Abstract

The incidence of anal squamous cell carcinoma (ASCC) is rising, and women with genital human papillomavirus (HPV) infection or HPV-associated high-grade squamous intraepithelial lesions (HSIL) are at high risk of developing ASCC. We conducted a cross-sectional study including 354 immunocompetent women referred for anal evaluation because of HPV infection or HSIL of the lower genital tract between 2019 and 2024. Participants were categorized according to the genital site affected by HSIL (uterine cervix, vagina, vulva/perineum/perianal region, or multicentric disease), and a control group of 99 immunocompetent women with genital HPV infection and/or low-grade SIL was included. All patients underwent anal high-risk HPV testing, liquid-based cytology, and high-resolution anoscopy when indicated. Overall, high-risk HPV infection and HSIL were identified in the anal canal in 62.5% and 5.6% of women, respectively. Women with multicentric disease showed a higher prevalence of anal HSIL compared with the control group (6/29, 20.7%, vs. 2/99, 2.0%; p = .031), and the other genital HSIL groups (11/182, 6.0% for cervical; 0/13, 0%, for vaginal; 1/31, 3.2% for vulvar HSIL; p = .003). Genital HSIL, particularly multicentric disease, was a strong marker of anal involvement. No HSIL/AIN occurred among women with a negative anal high-risk HPV test. Anal high-risk HPV testing alone showed optimal sensitivity (100%) and negative predictive value (100%) for the diagnosis of HSIL/AIN, whereas cytology alone had lower sensitivity (68.4%). Combining both tests did not improve accuracy and resulted in excessive referrals. High-risk HPV testing alone appears to be the most efficient approach for anal screening in women with genital HSIL.