Investigating the Potential Impact of HPV Vaccination on Uterine Cancer Incidence an Anatomical and Gynecological Approach: A Global and Regional Analysis

Abstract

Background: Uterine cancer, largely endometrial carcinoma, is among the most common gynecological malignancies worldwide, with incidence and mortality exhibiting marked geographical disparities. Recent trends highlight a rising incidence in both high-income countries (HICs) and low- and middle-income countries (LMICs), with obesity, elevated body mass index (BMI), and sociodemographic shifts identified as key risk factors. Histopathologically, endometrioid adenocarcinomas remain strongly associated with metabolic risk profiles, while aggressive non-endometrioid subtypes (such as uterine serous carcinoma, clear cell carcinoma, and carcinosarcoma) disproportionately drive mortality. Although human papillomavirus (HPV) vaccination primarily targets cervical carcinogenesis, emerging evidence suggests broader oncological and histopathological benefits in modifying gynecological cancer risk.

Methods: A systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, identifying 11 eligible studies from global databases and reference lists. Eligible studies included global burden analyses, regional cancer registry reports, risk factor evaluations, and narrative reviews addressing preventive strategies, including HPV vaccination.

Results: Global evidence demonstrates a steadily increasing incidence of uterine cancer, particularly in HICs, while LMICs experience rising mortality due to delayed diagnosis and limited oncological treatment infrastructure. Obesity and high BMI were consistently identified as dominant modifiable risk factors across datasets. Age–period–cohort analyses revealed increasing incidence among younger cohorts. Two reviews emphasized HPV vaccination as an indirect but valuable preventive strategy in gynecologic oncology.

Conclusion: The global burden of uterine cancer is rising, driven primarily by obesity and sociodemographic transitions, while health system inequities sustain high mortality in LMICs. Prevention strategies, including weight management,

lifestyle modification, metabolic risk reduction, and HPV vaccination, should be integrated into comprehensive cancer control programs to mitigate future burden