The aim of this study was to investigate a possible relation between oral squamous cell carcinoma (SCC), the presence of high-risk human papillomavirus (HR-HPV) DNA and p16 expression in young patients. Paraffin-embedded tumor blocks from 47 oral SCC of young (≤40-year old) patients were evaluated. The presence of HPV DNA in tumor specimens was analyzed by polymerase chain reaction (PCR) using GP5+/GP6+ generic primers (L1 region) followed by dot blot hybridization for HPV typing. When necessary, the HPV16 positivity was confirmed by PCR HPV16 E7-specific primers. Cases involving young patients were compared with 67 oral SCC from patients ≥50-year old (controls). Demographic and clinical data were collected to analyze patient outcomes. p16(ink4) expression was evaluated by immunostaining of tissue microarrays. HPV16 was detected in 22 (19.2%) cases; 15 (68.2%) young and 7 (31.8%) control patients, a statistically significant difference (p = 0.01). In 1 (1.7%) young group specimen, HPV DNA 16 and 18 was detected. p16 expression was observed in 11 (25.6%) cases from the young group and in 11 (19.6%) controls (p = 0.48). Association between HPV and p16 was verified, and it was statistically significant (p = 0.002). The higher prevalence of high-risk HPV types, especially HPV16, may be a contributing factor to oral carcinogenesis in younger individuals.

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