Low prevalence of HPV-driven head and neck squamous cell carcinoma in North-East Italy

• HPV DNA alone is not sufficient to demonstrate causality in HNSCC.
• Additional transformation markers are needed to correctly identify HPV-driven tumors.
• HPV prevalence in HNSCC shows large geographical variation, even within Europe.
• Few small studies investigated the relative prevalence of HPV in HNSCC in Italy.
• In North-East Italy 6% of HNSCC and 20% of OPSCC are HPV-driven.

ObjectivesTo investigate the frequency of Human papillomavirus (HPV)-driven head and neck squamous cell carcinoma (HNSCC) among patients living in North-East Italy, by assessing HPV-DNA positivity in all tumors and additional markers whenever possible.Material and methodsHPV types, viral load, viral RNA, HPV16/18 E6 protein and p16INK4a and pRb expression were determined in primary tumor tissues from 247 HNSCC patients. Tumor-specific HPV seropositivity was analyzed in 102 patients.ResultsTumor HPV-DNA prevalence was 8.5% overall (21/247) and 27% in oropharynx (17/63). HPV16 accounted for 95% of all HPV types found. Among HPV-DNA+ tumors, type-concordant HPV E6*I RNA prevalence was 79%. HPV DNA+ RNA+ tumors showed high viral load, up-regulated p16INK4a, down-regulated pRb and presence of HPV16 E6 protein. Eight cases showed tumor-specific HPV seropositivity, all type-concordant with the tumor. Tumors were defined as HPV-driven when positive for HPV-DNA plus 2 additional HPV transformation-related markers.ConclusionRelative prevalence of HPV-driven tumors (14 HPV16, 1 HPV58) was 6% overall and 20% among oropharyngeal cancers. In the oropharynx the HPV-driven group showed a trend for better survival versus the HPV-negative group.The relative prevalence of HPV-driven oropharyngeal cancer is low in North-East Italy as compared to Western and Northern Europe.