Associação entre a diversidade genética do hpv 16 e o prognóstico no câncer do colo do útero / Association between the genetic diversity of hpv 16 and the prognosis in cervical cancer

Introdução: O câncer do colo do útero (CCU) acontece em decorrência da infecção crônica e persistente por tipos oncogênicos do papilomavírus humano (HPV) na genitália feminina. Sua incidência ainda é alta em países em desenvolvimento como o Brasil, onde o diagnóstico muitas vezes é realizado em estádios avançados. O HPV 16 é o tipo mundialmente mais comum no CCU. O estudo da associação das diferentes linhagens do HPV 16 à sobrevida global e livre de doença do CCU pode contribuir na compreensão do comportamento das diferentes linhagens do HPV 16 em relação ao prognóstico. Objetivo: Avaliar o prognóstico de mulheres com câncer do colo do útero tratadas em uma Instituição brasileira, em relação às linhagens do HPV16. Métodos: Os dados desta análise são provenientes de uma coorte prospectiva de 334 mulheres com CCU tratadas no INCA (Rio de Janeiro) recrutadas entre julho de 2011 e março de 2014. A identificação das linhagens do HPV 16 foi realizada em amostra do tecido tumoral. A diversidade genética do HPV 16 foi representada por 218 casos da linhagem A, 10 da linhagem B, 10 da linhagem C e 96 da linhagem D. Além das linhagens do HPV 16, a idade, tipo histopatológico, estadiamento e completude de tratamento foram avaliados em relação ao prognóstico do CCU. Resultados: A idade mediana foi de 48 anos. O tipo histopatológico mais frequente foi o carcinoma epidermoide (82,3%), seguido do adenocarcinoma. O estadiamento com doença localmente avançada foi o mais comum nesta amostra, sendo representado por percentuais semelhantes nos estádios II e III (36,2% e 37,7%), seguido do estádio inicial I (19,2%) e pelo estadiamento IV, com doença à distância (6,9%). Apenas 187 mulheres completaram o tratamento. As variáveis idade, tipo histológico, estadiamento e completude de tratamento estiveram associadas com maior risco de morte, o que não ocorreu com a variável linhagem do HPV 16. Em relação à idade, a cada acréscimo de um ano de vida, houve aumento de aproximadamente 1% no risco de morte. Outros tipos histopatológicos (carcinoma pouco diferenciado, adenoescamoso, neuroendócrino e sarcoma) mostraram um maior risco de óbito em relação ao adenocarcinoma. O carcinoma epidermoide também representou maior risco de morte do que no adenocarcinoma, embora sem significância estatística. As mulheres diagnosticadas com estadiamento avançado tiveram maior risco de morte, e as que não completaram o tratamento aumentaram em mais de duas vezes o risco de morrer. Conclusão: Esse estudo não encontrou associação entre as linhagens A, B, C e D do HPV 16 e o prognóstico do CCU.

Introduction: Cervical cancer (CC) occurs as a result of chronic and persistent infection by the oncogenic type of human papillomavirus (HPV) in the female genitalia. Its incidence is still high in developing countries like Brazil, where the diagnosis is often performed in advanced stages. HPV 16 is the most common type in CC worldwide. Studying the association of different HPV 16 lineage with overall and disease-free survival in CC may contribute to understanding the behavior of different HPV 16 lineage in relation to prognosis. Objective: To evaluate the prognosis of women with cervical cancer treated at a Brazilian institution, in relation to HPV16 lineage A, B, C and D. Methods: The data from this analysis are from a prospective cohort of 334 women with CC treated at INCA (Rio de Janeiro) recruited between july 2011 and march 2014. Identification of HPV 16 lineage was performed on a sample of tumor tissue. The genetic diversity of HPV 16 was represented by 218 cases of the A lineage, 10 of the B lineage, 10 of the C lineage and 96 of the D lineage. In addition to the HPV 16 lineages; age, histopathological type, staging and completeness of treatment were evaluated in association with the prognosis of CC. Results: The median age was 48 years. The most frequent histopathological type was squamous cell carcinoma (82.3%), followed by adenocarcinoma. Staging with locally advanced disease was the most common in this sample, being represented by similar percentages in stages II and III (36.2% and 37.7%), followed by initial stage I (19.2%) and by stage IV, with distant disease (6.9%). Only 187 women completed the treatment. The variables age, histological type, staging and completion of treatment were associated with a higher risk of death, which did not occur with the variable HPV 16 lineage. Regarding age, with each increase of one year, there was an increase of approximately 1% in the risk of death. Other histopathological types (poorly differentiated, adenosquamous, neuroendocrine and sarcoma) showed a higher risk of death compared to adenocarcinoma. Squamous cell carcinoma also represented a higher risk of death than adenocarcinoma, although without statistical significance. Women diagnosed with advanced staging had a higher risk of death, and those who did not complete treatment increased their risk of dying by more than twice. Conclusion: This study found no association between HPV 16 lineage A, B, C and D and CC prognosis.

Surgical treatment of microinvasive cervical cancer: analysis of pathologic features with implications on radicality.

OBJECTIVES: To evaluate pathologic features with implications on surgical radicality in women treated with radical hysterectomy and pelvic lymphadenectomy for cervical cancer stage IA1 with lymph vascular space invasion (LVSI) and stage IA2 by correlating findings in conization and hysterectomy specimens. METHODS: Women with cervical cancer stage IA1 with LVSI and stage IA2 diagnosed by loop electrosurgical excisional procedure or cold knife conization were treated with radical hysterectomy and pelvic lymphadenectomy from January 1999 to December 2011 in 2 institutions. RESULTS: Fifty patients were enrolled: 40 with stage IA2 and 10 with stage IA1 with LVSI. Median age was 43 (30-67) years. All patients underwent cervical conization for diagnosis (45 loop electrosurgical excisional procedure, 5 cold knife). Lymph vascular space invasion was detected in 15 patients (30%). Two patients had positive pelvic nodes. No parametrial involvement was detected in the entire cohort. Positive margins were present in 35 patients, and residual disease was detected in 22 patients (44%). Positive margins predicted residual disease at radical hysterectomy (P = 0.02). Medium follow-up time was 51 months. One patient developed a pelvic recurrence, and there were no disease-related deaths. CONCLUSIONS: Patients with positive margins in cone biopsy specimens have an increased risk of residual disease at radical hysterectomy and require careful evaluation before conservative surgery. Pelvic lymph node evaluation is essential because lymph node metastasis may occur even in early stages. The lack of parametrial invasion in this study reinforces the knowledge that the select group of patients with microinvasive cervical carcinoma stages IA1 LVSI and stage IA2 have a very low risk of parametrial infiltration. Less radical surgery can be carefully considered for these patients.