Population-based patterns of human papillomavirus infections and cervical cancer incidence, driver mutations and overall survival

Background : Human papillomavirus (HPV) infection is the primary cause of cervical carcinoma. Variations in HPV prevalence, tumor genomic alterations, and survival outcomes across population groups remain incompletely characterized. Understanding the interplay of viral and host tumor biology is essential to optimize prevention and treatment in cervical cancer. Methods : High-risk HPV prevalence was evaluated in non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic (HSP) females aged 18-59 years using the National Health and Nutrition Examination Survey (NHANES, 2005-2016). Age-adjusted incidence of cervical cancer was evaluated using data from 21 regions in SEER (2004-2020). Somatic driver mutations were analyzed in tumors from patients with cervical cancer using the Genomics Evidence Neoplasia Information Exchange (GENIE v16.0). Overall survival was examined using Kaplan-Meier and Cox regression models among stage I-IV cervical cancer cases in the National Cancer Database (NCDB, 2004-2020). Results : Among 11,033 NHANES participants, high-risk HPV prevalence was similar in White and Hispanic women but higher in Black women (2.1-fold higher odds of any HPV infection; 1.5-fold higher odds of HPV16/18). Fig 1A shows the higher distribution of high-risk HPV genotypes individually and concurrent high-risk infections in NHB patients compared with either HSP or NHW patients. Data from SEER shows that age-adjusted incidence of cervical cancer was higher in both HSP and NHB patients compared with NHW patients. Rates declined in all groups from 2004-2000 (Fig 1B). Fig 1C displays somatic mutations in tumors from 595 cervical cancer patients in GENIE. BRD4, ERBB3, MTOR, and GRM3 mutations were more frequent in NHB than NHW patients. ERBB3, CIC, PIK3R1, and PI3K pathway alterations were enriched in NHB compared with HSP patients, whereas SMARCA4, CIC, KDM5C, and RANBP2 mutations were more common in White than Hispanic patients. In 117,170 NCDB cases, 5-year survival was 76% for HSP, 69% for NHW, and 60% for NHB patients (Fig 1D, p<0.0001). Compared with HSP women, mortality risk was 40% worse for NHW and 91% worse for NHB patients (p<0.001). Conclusions : Differences in HPV infection pattern are linked with cervical cancer incidence, somatic mutations, and survival, reflecting biologic and clinical heterogeneity across populations. Integrating viral genotyping with incidence rates and tumor molecular profiling may inform precision prevention, risk assessment, and personalized treatment to improve outcomes for all patients. Translational Relevance : This study links viral, incidence, genomic and survival data across multiple national datasets to reveal population-level variations in cervical cancer. These insights support efforts to enhance HPV vaccination, early detection, and individualized prevention, screening and therapeutic decision-making.