Universidade Federal de Goiás (UFG), Programa de Pós-Graduação em Ciências da Saúde (PPGCS), Faculdade de Medicina (FM) e Instituto de Patologia Tropical e Saúde Pública (IPTSP), Goiânia, GO, Brasil.
Pontifícia Universidade Católica de Goiás (PUC/GO), Programa de Pós-Graduação em Ciências Ambientais e Saúde (MCAS) e Escola de Ciências Médicas, Farmacêuticas e Biomédicas (ECMFB), Goiânia, GO, Brasil.
PLoS One. 2020 Jun 25;15(6):e0235065. doi: 10.1371/journal.pone.0235065. eCollection 2020.
Human papillomavirus (HPV) infection is associated with the development of anogenital and head and neck cancers. In recent years a potential role of HPV in colorectal cancer (CRC) has been suggested.
To investigate the presence of HPV in colorectal carcinomas and to study the role of p16INK4a as a marker of transcriptionally active HPV infection. In addition, to investigate the correlation between these findings and the CRC prognostic factors.
Case control study with 92 cases of colorectal cancers, 75 controls of normal tissue adjacent to the tumor, and 30 controls of precursor lesions, including polyps and colorectal adenomas. Paraffinized samples were used, HPV detection and genotyping were performed by PCR and reverse hybridization by using the INNO LIPA kit, with SPF10 plus primers. The expression of the p16INK4a protein was investigated using immunohistochemistry. Data analysis was performed using descriptive, univariate statistics and survival curves were calculated by using the Kaplan Meier and log-rank method.
HPV was detected in 13% of the cases and the most prevalent genotype was HPV 16. HPV DNA was not detected in either control groups. The high expression of p16INK4a was observed in 30% of the cases, but it was not associated to the presence of HPV. The overall survival was 53.3% and was influenced by prognostic factors such as later stage, lymph node and distant metastasis.
Based on these results, HPV is unlikely to be involved in colorectal carcinogenesis and p16INK4a expression is not a relevant marker of transcriptionally active HPV infection in CRC.
人乳头瘤病毒（HPV）感染与肛门生殖器和头颈部癌症的发展有关。近年来，HPV 与结直肠癌（CRC）的潜在关系已被提出。
研究 HPV 在结直肠癌中的存在情况，并研究 p16INK4a 作为 HPV 转录活性感染的标志物的作用。此外，还研究了这些发现与 CRC 预后因素之间的相关性。
采用病例对照研究，共纳入 92 例结直肠癌患者、75 例肿瘤旁正常组织对照和 30 例息肉和结直肠腺瘤等癌前病变对照。使用石蜡包埋样本，采用 PCR 和反向杂交法，使用 INNO LIPA 试剂盒和 SPF10 加引物检测 HPV 并进行基因分型。采用免疫组织化学法检测 p16INK4a 蛋白的表达。数据分析采用描述性、单变量统计，通过 Kaplan-Meier 和对数秩检验计算生存曲线。
在 13%的病例中检测到 HPV，最常见的基因型是 HPV 16。在两个对照组中均未检测到 HPV DNA。p16INK4a 的高表达在 30%的病例中观察到，但与 HPV 的存在无关。总体生存率为 53.3%，并受到预后因素的影响，如晚期、淋巴结和远处转移。
基于这些结果，HPV 不太可能参与结直肠癌的发生，p16INK4a 表达不是 CRC 中 HPV 转录活性感染的相关标志物。
