Risk factors and cytology performance for high-grade anal intraepithelial neoplasia in young adults: a cohort study

Background Human Papilloma Virus (HPV)-related high-grade anal intraepithelial neoplasia (AIN) is the precursor of anal cancer. There are limited data identifying factors that influence AIN progression in adults eligible for HPV vaccines. Methods A single-center cohort study including persons aged 18-45 years as of 2020 followed at the University of Pittsburgh Medical Center Anal Dysplasia Clinic (January 2020-December 2024), each with at least one anal cytology paired with histopathology or high-resolution anoscopy (reference standard). A subset with an initial non-HSIL result and ≥2 visits was followed longitudinally to assess progression to HSIL. Logistic regression identified factors associated with HSIL; Cox proportional hazards regression assessed progression to HSIL. Results We included 238 individuals (191 with HIV and 47 without), with median age 37 years, 16% female sex at birth, and median age at HPV vaccination series initiation of 27 years, with 79 (82%) of vaccinated patients receiving all three doses. Among 507 paired cytology-reference results, anal cytology had low-moderate sensitivity (55%) and specificity (82%), but an acceptable negative predictive value of 96% for HSIL on the reference standard (ref-HSIL). In the full cohort, the risk factor for ref-HSIL was ASC-H (atypical squamous cells, cannot exclude HSIL) or HSIL on cytology (adjusted odds ratio [aOR] 5.95, p < 0.001). In PWH, lower nadir CD4 count was associated with higher risk of ref-HSIL. Seven individuals with initial non-ref-HSIL progressed to ref-HSIL, all PWH with nadir CD4 <300 cells/µl; higher nadir CD4 was protective against progression (adjusted hazard ratio 0.43 per 100 cells/µl, p = 0.002) while current smoking was a risk factor (aHR 5.09, p = 0.05). Conclusions Anal cytology alone is not sensitive for HSIL detection in younger adults. Low nadir CD4 + count and current smoking identify patients needing closer surveillance.