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Abstract Introduction: Persistent infection with a high-risk HPV (HR-HPV) type causes cervical cancer and many other cancers in both men and women. Our published data have shown that the distribution of specific HPV16/35 sublineages and genetic variants differ around the world and confer greater risk of cervical precancer/cancer in the populations where the virus is thought to have originated and coevolved. More studies are needed to evaluate the relationship between race/ethnicity, HR-HPV genetic variation, and precancer/cancer risk. Objective: To evaluate HPV45 and HPV52 genetic variation, and how it relates to a woman’s race/ethnicity and cervical precancer/cancer risk, using HPV whole-genome sequencing of 774 HPV45+ and 719 HPV52+ women in the NCI-Kaiser Permanente Northern California (KPNC) HPV Persistence and Progression cohort; and compared to HPV16/35. Methods: We viral genome sequenced 557 HPV45+ and 345 HPV52+ controls (women with benign infections ≤CIN1), and 94 HPV45+ and 227 HPV52+ precancer/cancer cases (CIN3+). We evaluated HPV45 and HPV52 prevalence for each type by a woman’s self-reported race/ethnicity, and compared them to HPV16 and HPV35 using existing comparable NCI-KPNC data. To assess associations between HPV45 and HPV52 genetic variation (viral sublineages and SNPs) and infection outcome, we used Fisher’s Exact Tests and logistic regression to estimate the OR and 95% CI. Results: For HPV45, we determined that sublineages have varying histology-specific precancer/cancer risk (ORs ranged from 2-14), and that the sublineage distribution significantly varied by race/ethnicity (p 0. 001). By race, the HPV45 A2 sublineage was most prevalent in Asian/PI women and was associated with the highest risk of CIN3+ in these women compared to other races/ethnicities (OR=5. 7, 95% CI=1. 5-29. 4), while the B2 sublineage was associated with increased risk of CIN3+ in Black women only (OR=6. 1, 95% CI=1. 2-33. 6). The prevalence of each HR-HPV type (HPV16/35/45/52) significantly varied by race/ethnicity (p 0. 001). For each type, White was the most reported race/ethnicity; however, Black women were a greater proportion of the HPV35+ cases compared to other types (15% vs 8-10%), and Asian/PIs were a greater proportion of HPV52+ cases (26% vs 10-13%). HPV52 genome analyses are still underway; we will present the complete study results (i. e. , sublineage risk by race) at AACR. Conclusions: We conducted the largest studies of HPV45 and HPV52 genome variation to date. We demonstrate that specific HPV45 sublineages vary by race and are associated with an increased risk of precancer/cancer for specific races/ethnicities, and that HPV52 infection has a greater prevalence in Asian/PI women compared to other racial groups. Our data suggest that certain HR-HPV types and specific sublineages of these types are more common in specific racial/ethnic groups and potentially linked to differing risks by race. Citation Format: Aimee J. Koestler, Chase W. Nelson, Meredith Yeager, Zigui Chen, Laurie Burdett, Sambit K. Mishra, Michael Dean, Elizabeth Suh-Burgmann, Thomas Lorey, Phillip E. Castle, Mark Schiffman, Lisa Mirabello. HPV45 and HPV52 prevalence, within-type variants, and precancer/cancer risks differ by race/ethnicity abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 3948.
Koestler et al. (Fri,) studied this question.