Contemporary High-risk Human Papillomavirus Genotype Distribution and Associated Cytologic Findings Using Extended Human Papillomavirus Genotyping

OBJECTIVES: In January 2024, our laboratory implemented a human papillomavirus (HPV) assay that detects 14 high-risk HPV (hrHPV) genotypes-6 individually and 8 in 3 pooled groups. We evaluated genotype-specific infections and cytologic outcomes over 1 year to assess trends in HPV-related pathology. METHODS: After institutional review board exemption, a retrospective review of hrHPV tests and corresponding Papanicolaou cytology diagnoses of positive hrHPV tests from January to December 2024 was performed. RESULTS: Of 43,017 HPV tests, 3,771 (8.8%) were hrHPV-positive. Among 3,015 hrHPV-positive cases with corresponding cytologic diagnoses, 2,374 (78.7%) and 641 (21.3%) exhibited single hrHPV detections and multiple-genotype infections, respectively. Within the multiple-genotype group, HPV16 was detected in 129 cases-19 with HSIL-and HPV18 was present in 68 cases-8 with HSIL. Pooled genotypes 56/59/66 and 35/39/68 were each detected in 328 cases-6 total with HSIL. Single-genotype infections exhibited similar trends. Although multiple-genotype infections showed a higher frequency of high-grade lesions, these cases were predominantly associated with the presence of HPV16 and/or HPV18. CONCLUSIONS: Extended genotyping demonstrated that pooled non-16/18 genotype groups comprised nearly half of hrHPV-positive infections and were predominantly associated with negative for intraepithelial lesion or malignancy, atypical squamous cells of undetermined significance, and low-grade squamous intraepithelial lesions on cytology. Although HPV16 and 18 remained the genotypes most strongly associated with high-grade cytologic abnormalities, the high prevalence of non-16/18 genotypes highlights the importance of genotype surveillance in the postvaccination era. These findings support the value of extended genotyping for risk stratification and population-level monitoring of evolving HPV epidemiology.