The high-risk human papillomavirus (HPV) infection represents one of the main etiologic pathways of penile carcinogenesis in approximately 30-50 % of cases. Several techniques for the detection of HPV are currently available including Polymerase chain reaction-based techniques, DNA and RNA in situ hybridization (ISH), p16 immunohistochemistry (IHC). The multiplex HPV RNA ISH/p16 IHC is a novel technique for the simultaneous detection of HPV E6/E7 transcripts and p16INK4a overexpression on the same slide in a single assay. The main aim of this study was to evaluate the discrepancy of p16 IHC expression relatively to HPV RNA ISH in penile cancer tissue.
We collected a series of 60 PCs. HPV has been analysed through the RNA ISH, p16 IHC and the multiplex HPV RNA ISH/p16 IHC.
The multiplex HPV RNA ISH /p16 IHC results in the series were in complete agreement with the previous results obtained through the classic p16 IHC and HPV RNA scope carried out on two different slides. The multiplex HPV RNA ISH /p16 IHC showed that HPV positivity in our series is more frequently in usual squamous cell carcinoma than in special histotypes (19 out of 60 - 15 %- versus 6 out of 60 - 10 %-), in high-grade than in moderate/low grade carcinomas (6 out of 60 - 10 %- versus 4 out of 60 - 6.7 %-). In addition, our data revealed that in 5 out of 20 cases with p16 high intensity expression is not associated with HPV RNA ISH positivity.
Our findings emphasize that the use of p16 as a surrogate of HPV positivity was unsuccessful in approximatively 8 % of cases analysed in our series. Indeed, p16 IHC showed a sensitivity of 100 % and a specificity of 71 %, with a positive predictive value (PPV) of 54 % and a negative predictive value of 100 %; when considering high intensity, p16 IHC showed a sensitivity of 100 %, a specificity of 89 %, with a PPV of 75 % and NPV of 100 %. Since HPV positivity could represent a relevant prognostic and predictive value, the correct characterization offered by this approach appears to be of paramount importance.
Infectious agents and cancer. 2021 Mar 31*** epublish ***
Federico Zito Marino, Rosalaura Sabetta, Francesca Pagliuca, Matteo Brunelli, Gabriella Aquino, Sisto Perdonà, Gerardo Botti, Gaetano Facchini, Francesco Fiorentino, Giovanni Di Lauro, Marco De Sio, Ferdinando De Vita, Giorgio Toni, Rodolfo Borges Dos Reis, Luciano Neder, Renato Franco
Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", Complesso di Santa Patrizia, Via Luciano Armanni, 5, 80138, Naples, Italy., Department of Pathology, University of Verona, Verona, Italy., Pathology Unit, Istituto Nazionale Tumori, Fondazione G. Pascale, IRCCS, 80131, Naples, Italy., Department of Urology, Istituto Nazionale Tumori, Fondazione G. Pascale, IRCCS, 80131, Naples, Italy., Medical Oncology Unit, S.M. delle Grazie Hospital, Via Domitiana, 80078, Pozzuoli, NA, Italy., Pathology Unit, S.M. delle Grazie Hospital, Via Domitiana, 80078, Pozzuoli, NA, Italy., Urology Unit, S.M. delle Grazie Hospital, Via Domitiana, 80078, Pozzuoli (NA), Italy., Urology Unit, Department of Woman, Child and General and Specialized Surgery, University of Campania 'Luigi Vanvitelli, 80138, Naples, Italy., Division of Medical Oncology, Department of Precision Medicine, School of Medicine, "Luigi Vanvitelli" University of Campania, Naples, Italy., Laboratoire Central d'Anatomie pathologique, Hôpital universitaire de Nice, Université Côte d'Azur, 06000, Nice, France., Department of Surgery and Anatomy, Urology Division, Ribeirao Preto School Medicine, University of São Paulo, 14049 900, Ribeirao Preto, Brazil., Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, 14049 900, Ribeirão Preto, SP, Brazil., Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", Complesso di Santa Patrizia, Via Luciano Armanni, 5, 80138, Naples, Italy. .