Associations between genetic HPV 16 diversity and cervical cancer prognosis

Patrícia Patury, Fabio B. Russomano, Luiz F. L. Martins, Miguel Angelo Martins Moreira, Raquel B. M. Carvalho, Nadia Roberta Chaves Kappaun, Liz Maria de Almeida
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Abstract

Introduction Cervical cancer (CC) arises as a result of chronic and persistent female genitalia infection by different oncogenic human papillomaviruses (HPV). The incidence of this disease is still high in developing countries such as Brazil, where the diagnosis is often made in advanced stages. HPV 16 is the most common type of CC worldwide. Studies concerning the association of different HPV 16 lineages with overall and disease-free CC survival rates can contribute to further understanding the behavior of different HPV 16 lineages concerning the prognosis of CC cases. Objective Assess the CC prognosis of patients treated in a Brazilian institution with regard to HPV16 strains. Methods Data were obtained from a prospective cohort of 334 CC patients recruited between July 2011 and March 2014 and treated at the Brazilian National Cancer Institute (INCA), in Rio de Janeiro, Brazil. HPV 16 lineages were identified in tumor tissue samples. Genetic HPV 16 diversity comprised 218 cases of lineage A, 10 of lineage B, 10 of lineage C and 96 of lineage D. In addition to HPV 16 lineages, age, histopathological type, staging, and treatment completion were evaluated regarding CC prognosis. Results Median patient age was 48 years old. The most common histopathological type was squamous cell carcinoma (82.3%), followed by adenocarcinoma. Locally advanced disease staging was the most frequently detected, represented by similar stage II and III percentages (36.2% and 37.7%), followed by initial stage I (19.2%) and stage IV presenting distant disease (6.9%). Only 187 patients completed CC treatment. Age, histological type, staging, and treatment completion were associated with a higher risk of death, which was not observed for the HPV 16 lineage variable. With regard to age, each one year of life increase led to about a 1% increase in risk of death. Other histopathological types (poorly differentiated carcinoma, adenosquamous, neuroendocrine and sarcoma) were associated with a higher risk of death compared to adenocarcinoma. Squamous cell carcinoma also represented a higher risk of death compared to adenocarcinoma, albeit non-statistically significant. Patients diagnosed in advanced stages exhibited a higher risk of death, and those who did not complete treatment exhibited an over 2-fold increased risk of death. Conclusion This study found no associations between HPV 16 lineages A, B, C and D and CC prognosis.
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基因 HPV 16 多样性与宫颈癌预后之间的关系
导言 宫颈癌(CC)是女性生殖器长期持续感染各种致癌人类乳头瘤病毒(HPV)的结果。在巴西等发展中国家,这种疾病的发病率仍然很高,而且通常在晚期才能确诊。HPV 16 是全球最常见的 CC 类型。有关不同 HPV 16 株系与 CC 总存活率和无病存活率关系的研究有助于进一步了解不同 HPV 16 株系对 CC 病例预后的影响。目的 评估在巴西一家机构接受治疗的 CC 患者的 HPV16 株系预后。方法 从 2011 年 7 月至 2014 年 3 月间招募的 334 名 CC 患者的前瞻性队列中获取数据,这些患者在巴西里约热内卢的巴西国家癌症研究所(INCA)接受了治疗。在肿瘤组织样本中确定了 HPV 16 株系。除了HPV 16系外,还对CC预后的年龄、组织病理学类型、分期和治疗完成情况进行了评估。结果 患者年龄中位数为 48 岁。最常见的组织病理学类型是鳞状细胞癌(82.3%),其次是腺癌。最常发现的疾病分期是局部晚期,II期和III期的比例相似(36.2%和37.7%),其次是初始I期(19.2%)和出现远处疾病的IV期(6.9%)。只有 187 名患者完成了 CC 治疗。年龄、组织学类型、分期和完成治疗与较高的死亡风险有关,而在HPV 16系变量中没有观察到这一点。在年龄方面,每增加一岁,死亡风险就会增加约1%。与腺癌相比,其他组织病理学类型(分化不良癌、腺鳞癌、神经内分泌癌和肉瘤)的死亡风险更高。与腺癌相比,鳞状细胞癌的死亡风险也更高,尽管没有统计学意义。晚期患者的死亡风险更高,未完成治疗的患者的死亡风险增加了 2 倍多。结论 本研究未发现 HPV 16 A、B、C 和 D 族系与 CC 预后之间存在关联。
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