Diagnóstico de los carcinomas orofaríngeos relacionados con el virus del papiloma humano (VPH)detección viral mediante técnicas comerciales de uso clínico y análisis de su valor pronóstico

Abstract

Head and neck carcinomas are the sixth most common cancer worldwide. Although these types of cancer are typically associated to alcohol and tobacco exposure, there is an increasing incidence of oropharyngeal cancers attributed to human papillomavirus (HPV) related oncogenesis. HPV-related oropharyngeal carcinomas (OPC) show pathological, clinical, and prognostic differential characteristics, and could benefit from new treatment strategies able to reduce treatment-related toxicity and improve the quality of life and survival of the patients. However, HPV testing for the diagnosis of HPV-associated OPC is still challenging, and at the moment, it has not been established the test or testing algorithms to reliably perform the laboratory diagnosis of this type of carcinomas. In our study, we performed a comparative evaluation of commercial HPV-testing assays in formalin-fixed paraffin-embedded (FFPE) samples from oropharyngeal carcinomas diagnosed at Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA) (Murcia, Spain) between 2005-2016, and analyzed their prognostic value. Several diagnostic approaches were considered, comprising five DNA-HPV detection assays covering different biological and molecular targets [HPV Xpert® (Cepheid), Anyplex® II HPV28 Detection (Seegene), CLART® HPV4 (Genomica), INNO-LiPA® HPV Genotyping Extra II (Fujirebio) and AmpFire® (Atila Biosystems)], two viral mRNA E6/E7 detection assays [PreTect® HPV-Proofer (NorChip) and QuantiVirus® HPV E6/E7 RNA (DiaCarta)] and the immunohistochemical detection of p16 overexpression. Our study reveals that the evaluated assays obtain, to different extents, concordant results for HPV-detection, and support their suitability for their use on the diagnosis of HPV-related OPC. Among them, the HPV-DNA detection assays provide a better prognostic value for this type of carcinomas, while the absence of p16 overexpression is associated with the negativity of the HPV-detection assays. These results suggest the suitability of a two-step algorithm for the reliable laboratory diagnosis of HPV-related OPC, consisting on the detection of p16 overexpression followed by HPV-DNA detection.