The Role of Human Papillomavirus Genotypes on Anal Squamous Intraepithelial Lesions Among Gay, Bisexual and Other Men Who Have Sex With Men Living With HIV: Beyond HPV‐16

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Abstract
Persistent high‐risk human papillomavirus (hHPV) infection, especially HPV‐16, plays a central role in the development of high‐grade squamous intraepithelial lesions (HSIL). This study aimed to evaluate the performance of co‐testing (cytology and hHPV detection) in a real‐world cohort of men who have sex with men (MSM) and transgender women (TW) living with HIV. We conducted a prospective study (2017–2023) at a tertiary care center in Spain. MSM and TW living with HIV underwent screening with anal cytology and PCR‐based hHPV testing. High‐resolution anoscopy (HRA) with biopsy was performed in cases with abnormal cytology and/or hHPV positivity. Clinical, epidemiological, and HIV‐related data were collected to identify risk factors for abnormal cytology and biopsy. 734 cytologies were performed in 380 participants. Abnormal cytology was found in 34%, most commonly ASCUS. hHPV was detected in 63.1% of samples; HPV‐16 was the most prevalent genotype (19.4%), present in 60% of HSIL cytologies and 65% of AIN2–3 biopsies. Risk factors for abnormal cytology included nadir CD4 < 200 cells/μL (aOR 2.61), prior condylomas (aOR 2.66), and infection with any oncogenic HPV genotype (aOR 4.12). Among 91 HRAs, 29.6% showed AIN2–3% and 2.1% in situ carcinoma. HPV‐16, HPV‐52, and HPV‐66 were most frequently associated with abnormal findings in the cytology. In conclusion, anal HPV infection was prevalent in MSM and TW living with HIV. The genotypes most frequently associated with abnormal cytology and histopathological findings were HPV‐16, HPV‐52, and HPV‐66. These findings highlight the potential value of implementing co‐testing strategies in anal dysplasia screening for this high‐risk population.

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