Oral Human Papillomavirus Benign Lesions and HPV-Related Cancer in Healthy Children: A Systematic Review

SIMPLE SUMMARY: The present systematic review aimed to gain deeper insight into the epidemiology, clinical presentation, and histopathology of HPV-related benign and malignant lesions of the oral mucosa in pediatric patients to improve the multidisciplinary preventive and therapeutic management of oral and general healthcare. The emerging role of HPV in oral carcinogenesis in pediatric subjects, along with benign oral mucosal lesions and asymptomatic infections, brings HPV vaccination to the forefront specifically for this age group. ABSTRACT: The present systematic review aimed to assess the prevalence of oral HPV-related lesions, categorized as benign (verruca vulgaris “VV”, squamous cell papilloma “SP”, condyloma acuminata “CA”, and focal epithelial hyperplasia “FEH”) and malignant (oral squamous cell carcinoma “OSCC”), in descending order of occurrence in pediatric subjects (≤18 years of age). The secondary objectives were to evaluate the frequency and types of oral lesions described in relation to HPV genotypes and the HPV vaccine type (if any). The study protocol, compliant with the PRISMA statement, was registered at PROSPERO (CRD42022352268). Data from 60 studies, of which quality was assessed using the ROBINS-I tool, were independently extracted and synthesized. Along with seven poorly described benign HPV-related oral lesions that could not be categorized, a total of 146 HPV-related oral lesions, namely 47.26% (n = 69) VV, SP, and CA, 51.37% (n = 75) FEH, and 1.37% (n = 2) OSSC, were diagnosed in 153 pediatric subjects (M:F ratio = 1:1.4) with a mean age of lesion onset of 8.46 years. The viral genotypes detected were HPV-13 (30.61%), -6 (20.41%), -11 (16.33%), HPV-2 (12.24%), -32 (10.20%), -57 (6.12%), and -16 (4.08%). No HPV vaccination was reported in any case. Further studies should be conducted to evaluate the prevalence of HPV-related benign and malignant lesions and the potential role of HPV and associated vaccination in oral carcinogenesis in pediatric subjects.