Immunocompetency Status and Its Association With Multicentric Lower Anogenital Tract Dysplasia

Objective Multicentric, human papillomavirus (HPV) associated lower genital tract disease includes preinvasive and invasive lesions at multiple anatomic sites and can be synchronous or metachronous. Identifying patients with multicentric disease is crucial because of associated high treatment failure and recurrence. This study evaluates clinicopathologic patterns in immunocompetent and immunocompromised patients with multicentric lower anogenital disease. Materials and Methods Two-hospital retrospective study of 36 patients with histologic diagnoses of multicentric anogenital HPV-associated dysplasia was identified over a 25-year period. Patients were classified based on immune status: immunocompetent without HIV, immunocompetent with HIV, and immunocompromised. Histologic diagnoses, p16 immunohistochemistry (IHC), and in situ hybridization (ISH) for high-risk (HR) and low-risk (LR) HPV were reviewed. Results The most common sites of dysplasia were the anus (25%) and vulva (25%), with high-grade squamous intraepithelial lesions (HSIL) being the most frequent diagnosis (50%). Positive p16 IHC and HR-HPV ISH staining occurred in 71% and 81% of specimens, respectively. One-third of patients revealed a variation in IHC/ISH expression in lesions at the same anatomic sites at different time points. A significantly higher frequency of variation occurred in individuals living with HIV and immunocompromised individuals when compared to immunocompetent individuals. Conclusions This study supports the theory that some multicentric disease may arise from repeated infections with various HPV genotypes. The findings highlight the need for further research into genetic predispositions and other factors influencing the development of multicentric HPV-associated lesions in both immunocompetent and immunocompromised individuals.