Italian observational study on HPV infection, E6, and p16 expression in men with penile cancer

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Italian observational study on HPV infection, E6, and p16 expression in men with penile cancer Narcisa Muresu1, Giovanni Sotgiu1*  , Laura Saderi1, Illari Sechi2, Antonio Cossu1, Vincenzo Marras1, Marta Meloni1, Marianna Martinelli3, Clementina Cocuzza3, Francesco Tanda1 and Andrea Piana1

Abstract  Background:  Human Papillomavirus (HPV) infection is one of the most important causes of cancer. It can play a role in cervical and extra-cervical cancers. Penile cancer is rare, even if an increasing trend was recently reported. Aim of the present study was to assess the prevalence and distribution of HPV genotypes in cases of penile cancer diagnosed in Sardinia, Italy. Surrogate markers of HPV infection (i.e., E6 and p16 genes) were also evaluated in all cases. Methods:  An observational, retrospective study which recruited all cases of penile cancer diagnosed between 2002 and 2019 at a tertiary care hospital in Sardinia, Italy, was carried out. HPV-DNA detection and genotyping were performed by Real-time PCR. Specimens were tested for oncogene E6 mRNA and for p16(INK4a) expression. Results:  HPV prevalence was 28.1% (9/32); HPV-16 was the most prevalent genotype (7/9, 77.8%). p16INK4a positivity was found in 66.7% of the samples with a statistically significant difference between HPV-positive and -negative groups. E6-transcript was detected in 71% of the HPV-16 positive samples. The overall survival was not statistically different between HPV-positives and -negatives. Discussion:  The present study confirms the etiologic role of HPV in penile cancer and supports the adoption of vaccination strategies in men and women. Further studies should clarify the diagnostic and prognostic role of E6 and p16 proteins. Conclusion:  HPV infection can favor the occurrence of penile cancer, whose diagnosis and prognosis could be improved with the implementation of validated molecular techniques. Keyword:  HPV, Penile cancer, E6, p16, HPV-DNA Introduction Human Papillomavirus (HPV) is one of the leading causes of cancer, with ~ 690,000 new annual cases worldwide. HPV vaccination and PAP-testing (i.e., Papanicolau test) have significantly reduced the incidence of cervical carcinoma; however, an increasing trend of other HPV-related cancers (e.g., anogenital and head and neck cancers) has *Correspondence: [email protected] 1 Department of Medical, Surgical and Experimental Sciences, University of Sassari, Via Padre Manzella, 4, 07100 Sassari, Italy Full list of author information is available at the end of the article

been described worldwide. It has been estimated that > 90%, > 50%, 77%, and 25% of anal, penile, vaginal, and vulvar cancers are attributable to HPV, respectively [1]. Penile cancer is a rare disease in the general population, accounting for