Low Frequency of Human Papillomavirus in Strictly Site-Coded Oral Squamous Cell Carcinomas, Using the Latest NHI/SEER-ICD Systems: A Pilot Observational Study and Critical Review.

Vera Panzarella,Rodolfo Mauceri,Laura Maniscalco,Giuseppina Capra,Vito Rodolico,Ylenia Giardina,Giuseppina Campisi,Olga Di Fede

doi:10.3390/cancers13184595

Vera Panzarella, Rodolfo Mauceri + Show 6 more

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https://doi.org/10.3390/cancers13184595

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Abstract

Simple SummaryThe incidence of oropharyngeal squamous cell carcinomas (OPSCCs) has increased in the last decades, and this seems to be correlated to the infectious epidemiological trend of human papillomavirus (HPV). The prevalence of HPV-positive OPSCCs is approximately 70%, with involvement mainly of the tonsillar area. On the role of HPV in oral squamous cell carcinoma (OSCC), very few studies have investigated the prevalence of HPV in strictly site-codified OSCC, excluding the base of the tongue as distinct oropharyngeal entity. As a result, an inappropriate estimation of HPV infection in OSCC has been observed. We investigated HPV status, using a combination of detection methods, in a sample of 40 subjects with OSCC coded by the latest site classifications. Moreover, we performed a critical review of the studies with the same outcomes. The main finding of our investigation was a low frequency of HPV-positive OSCC, suggesting no significant HPV role in strictly oral carcinogenesis.The aim of this study was to evaluate HPV status in oral squamous cell carcinoma (OSCC), as coded by the latest classifications and applying a combination of detection methods used in clinical practice. Forty-two patients with suspect OSCC were consecutively recruited. Patients underwent an incisional biopsy for histological OSCC diagnosis and HPV identification by PCR DNA and p16 IHC. All lesions were coded by the latest ICD-0-3.2 site/histology classifications, as proposed for OSCC by the National Cancer Institute Surveillance, Epidemiology and End Results Programs. Moreover, a comparative analysis review, critically evaluated by the same site-coded systems and HPV detection methods, was performed. In 40 confirmed cases of OSCC, the frequency of HPV infection was 10% (4/40). Among positive patients, two cases were PCR DNA/p16 IHC positive (high-risk HPV 51, high-risk HPV 67), two cases were PCR DNA positive/p16 IHC negative (high-risk HPV 31 + 68, high-risk HPV 66). Applying the latest site coding systems for OSCC, the frequency of HPV infection in this study and in similar, reviewed investigations was low (from 3.3% to 12.5%). These results suggested no significant HPV role in oral carcinogenesis, particularly where an updated site-coded classification of OSCCs (categorically excluding the base of the tongue) had been performed.

Highlights

The incidence of oropharyngeal squamous cell carcinomas (OPSCCs) has increased considerably in the last four decades. This trend appears to be related to an incidence of human papillomavirus (HPV) infection: the prevalence of HPV-positive OPSCCs is approximately 70% (60% supported by HPV16/18 genotypes, and 10% supported by HPV31/33/45/52/58 genotypes) [1]
HPV-positive OPSCCs seem to have a better prognosis than HPV-negative OPSCCs due to a lower risk of local recurrence and an increased radio-chemo sensitivity [2,3]
It was possible to detect a percentage of false positives (p16 IHC positives in HPV polymerase chain reaction (PCR) DNA negative cases) in all nine studies, with a frequency ranging from 0% to 48%. Both the results described in the observational study and those relating to the critical review confirmed the risk of an overestimation of HPV positivity in all oral squamous cell carcinoma (OSCC) that had not been suitably distinguished by site, relating to the tongue, and the frequent false HPV status using only p16 as a detection technique

Summary

Introduction

The incidence of oropharyngeal squamous cell carcinomas (OPSCCs) has increased considerably in the last four decades. This trend appears to be related to an incidence of human papillomavirus (HPV) infection: the prevalence of HPV-positive OPSCCs is approximately 70% (60% supported by HPV16/18 genotypes, and 10% supported by HPV31/33/45/52/58 genotypes) [1]. HPV-related OPSCCs appear to occur predominantly on the tonsillar area and on the base of tongue, while HPV-negative OPSCCs, which are linked to traditional risk factors, tend to involve other oral and oropharyngeal sub-sites. HPV-positive OPSCCs seem to have a better prognosis than HPV-negative OPSCCs due to a lower risk of local recurrence and an increased radio-chemo sensitivity [2,3]. HPV detection rates still present a wide variation in OPSCCs, which is due to two compellingly interconnected reasons: (i) a nonunivocal topographical classification of the OPSCC; and (ii) the different and various HPV identification techniques used [6,7]

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