Prognóstico de pacientes portadores de carcinoma de pênis: papel de papilomavírus humano / Penile carcinoma: role of human papillomavirus on prognosis

RESUMO

O carcinoma espinocelular infiltrativo do pênis dissemina-se principalmente para os linfonodos regionais. O tratamento dessa neoplasia, na presença de metástases linfonodais, baseia-se na amputação e linfadenectomia bilateral. Não existe consenso, no entanto, em relação às linfadenectomias profiláticas. Considerando os altos índices de morbidade desse procedimento, a identificação de fatores prognósticos do tumor primário ajudaria na seleção dos reais candidatos à ressecção cirúrgica dos linfonodos regionais... Neste estudo avaliamos a importância prognóstica da presença do DNA do HPV no tumor primário de 82 pacientes, submetidos a amputação do pênis e linfadenectomia bilateral no Hospital A.C. Camargo, São Paulo, no período de janeiro de 1953 a dezembro de 1992. A presença do HPV foi relacionada a variáveis clínicas (idade, estado civil, raça, tempo de evolução da doença, antecedentes venéreos, estadiamento cT, estadiamento cN e cirurgia do tumor primário) e anatomopatológicas do tumor primário (grau de diferenciação, espessura do tumor, presença de permeação linfática e venosa, infiltração de corpos cavernosos, infiltração de uretra, presença de infiltrado mononuclear e eosinofílico e presença de coilocitose), assim como avaliada na sua provável interferência com a sobrevida e risco de óbito dos pacientes. O DNA do HPV foi detectado em 25 (30,5%) pacientes, sendo 18 (72%) HPV 16 e/ou 18, 3 (12%) HPV 31/33/35, 2 (8%) HPV 6/11, 1 (4%) HPV 45 e 1 (4%) HPV 51/52... Os resultados da presente investigação permitem concluir que, embora o HPV esteja associado com um certo número de carcinomas de pênis, a presença do DNA viral não parece influir na evolução da doença nem na sobrevida desses pacientes...(AU)

ABSTRACT

Squamous cell carcinoma of the penis spreads locally to ilioinguinal lymph nodes. In the presence of lymph node metastases, the gold standard for the treatment remains partial or total amputation of the penis, followed by bilateral lymphadenectomy. There is no consense, however, about prophylatic lymphadenectomies. Considering the high morbidity rates of this procedure, the identification of prognostic factors for the incidence of metastases could help to select candidates to lymphadenectomies. The human papillomavirus (HPV), recently recognized as a possible etiologic agent for preinvasive and invasive penile carcinomas, could be one of this factors. A retrospective study of 82 patients with penile carcinoma submitted to amputation and bilateral lymphadenectomy at A.C. Camargo Hospital, from 1953 to 1992, was undertaken to evaluate the possible prognostic value of HPV DNA. The relevance of HPV DNA presence was studied with other clinicopathological parameters (age, marital status, race, disease evolution time, previous venereal disease, staging, treatment of primary tumor, histological grade, tumor thickness, vascular embolization, corpora cavernosa and corpus spongiosum infiltration, urethral infiltration, mononuclear infiltrate, eosinophilic infiltrate and presence o f koilocytosis ), survival rates and risk o f death o f the patients. Overall, HPV DNA was detected in 30.5% (25/82) ofthe samples. Eighteen (72%) of 25 HPV DNA-positive tumors contained HPV 16 and/or 18, 3 (12%) had HPV 31/33/35, 2 (8%) HPV 6/11, 1 (4%) HPV 45 and 1 (4%) HPV 51152. The sensitivity and specificity of the presence of koilocytosis for viral infection diagnosis was of 54.2% and 50.8%, respectively, which correlates with the high false negative (27.5%) and false-positive ( 68.3%) rates. At univariate analysis, HPV detection rates were higher among younger (40ys or less) (p=0.046) and married patients (p=0.025). Patients with tumors HPV DNA-positive had less lymphatic embolization by neoplastic cells than HPV negative ones (p=0.007). Multiple logistic regression analysis revealed that HPV status was related only with lymphatic embolization (OR:0.27; IC:0.10-0.75) (p=0.012). There was no difference between HPV DNA-negative and HPV DNA-positive patients according to presence of lymph node metastases (p=0.386). HPV DNA was also not considered a risk factor for patients death (HR:1.85; CI 0.77-4.45). Disease specific survival rate at 5 and 1 O years for HPV DNA-negative and HPV DNA-positive patients were 68.4% and 69.1 %, respectively (p=0.830). The multivariate analysis revealed that only node status was significantly associated with disease specific survival (HR:8.25; CI 2.77-24.85). The lymphatic embolization by neoplastic cells (OR 10.82; CI 2.68-43 .59), clinicai staging N1 (OR 11.47; CI 1.50-87.64) and N3 (OR7.23; CI 1.10-47.26) were significant for the incidence of lymph node metastasis. Although HPV is associated with some penile carcinomas, the results of the present investigation suggest that HPV DNA does not influence prognosis in this neoplasm (AU)