Expressão imunohistoquímica de biomarcadores e sua relação com o Papiloma vírus humano em carcinomas de cabeça e pescoço

Abstract

Head and neck cancer is considered the sixth most prevalent neoplasm in the world, with more than six hundred thousand new cases diagnosed each year and the fifth most prevalent in Brazil, with more than one thousand five hundred people affected annually, being responsible, worldwide, by four percent of cancer mortality. The most common type is squamous cell carcinoma (CECP), its pathogenesis has been historically associated with tobacco and alcohol use, but in the last decades HPV infection has been associated with the disease. Defining the prognosis and risk of development, as well as the success of the treatment in response to a particular medication and/ or procedure, are the main reason for the identification of biomarkers, and their expression may reflect several processes in progress in tumor cells. Several studies have correlated the expression of survivin in solid tumors with a clinically unfavorable course of the disease, drug resistance, worse prognosis and shorter patient survival. p16 may provide evidence of the malignant potential of an injury, and its overexpression may be considered a favorable prognostic marker. Elevated PD-L1 expression may be an important facilitator for tumor growth and metastasis. The objective of this work was to identify, by immunohistochemistry, the levels of expression of p16, survivin and PD-L1 in samples of head and neck malignant lesions in the presence and absence of HPV viral infection and to relate them to the clinical findings of patients. Thirty-three tissue samples were used, obtained by biopsy of head and neck lesions, for diagnostic purposes, coming from the Oncology Service of the General Hospital of Caxias do Sul and from the Diagnose Laboratory database. Samples were retrospectively selected, having as selection criterion the presence of squamous cell carcinoma of the head and neck. The determination of the presence of HPV and viral typing was performed by the polymerase chain reaction method and the protein expression by immunohistochemistry. The results were evaluated considering the proportion of positive cells compared to the total number of cells in the field. The overexpression of p16 in CECPs may be indicative of the participation of HPV infection during the carcinogenesis process, being that the relationship between p16 overexpression and the presence of HPV infection was not observed in some of the evaluated cases, which may indicate: failure in the PCR achievement, not detecting the presence of HPV; the non-participation of HPV in the process of carcinogenesis; the synergism between the carcinogenic pathways HPV+ and HPV- (smoking/alcoholism). In addition, the overexpression of p16 in conjunction with the expression of survivin and/or PD-L1 indicates an intermediate behavior, between cancers HPV+ and HPV- (pathway carcinogenic smoking/alcoholism). p16, survivin and PD-L1 are indicative of the carcinogenic pathway HPV+, and may predict if there was synergism between carcinogenic pathways as well as indicate the behavior of tumors, however should not be used in isolation, including PCR for HPV. The biomarkers evaluated in this study may be useful in the clinical management of patients, besides helping in the development of new therapeutic modalities, being necessary to obtain a greater number of cases and information on the expression of these biomarkers.