Association between HPV infection and prostate cancer in a Mexican population

Abstract The aim of this study was to evaluate the association between prostate cancer (PCa) and Human papillomavirus (HPV) infection in the Mexican population. We studied 356 paraffin-embedded tissues from unrelated Mexican men with PCa or benign prostatic hyperplasia (BPH), with the latter serving as control. HPV detection was performed by polymerase chain reaction (PCR) using universal primers, and viral genotypes were detected using sequencing or multiplex PCR. Light microscopy analyses enabled the identification of koilocytes in samples subsequently analyzed for HPV detection by in situ PCR and for p16-INK4A expression by immunohistochemistry. The results showed that high risk- (HR) HPVs were detected in 37/189 (19.6%) PCa specimens compared to 16/167 (9.6%) of BHP specimens (odds ratio 2.3; 95% CI= 1.2 to 4.3; p=0.01). These data suggest HR-HPV may play a role in PCa. HPV 52 and 58 were the most frequent genotypes (33 and 17%, respectively) detected in the population studied. Koilocytes were detected in all in situ PCR-HPV-positive samples, representing a pathognomonic feature of infection, and we observed the overexpression of p16-INK4A in HPV-positive samples compared to HPV-negative samples, indirectly suggesting the presence of HR-HPV E7 oncoprotein. These results suggest that HPV infection plays an important role in prostate cancer development.

摘要 本研究旨在评估墨西哥人群中前列腺癌（prostate cancer, PCa）与人乳头瘤病毒（Human papillomavirus, HPV）感染的相关性。我们纳入356份来自无亲缘关系的墨西哥男性的石蜡包埋组织样本，这些受试者均患有前列腺癌或良性前列腺增生（benign prostatic hyperplasia, BPH），其中良性前列腺增生患者作为对照。HPV检测采用通用引物开展聚合酶链反应（polymerase chain reaction, PCR），病毒基因型则通过测序或多重PCR进行鉴定。光学显微镜分析可识别挖空细胞，随后对携带挖空细胞的样本分别通过原位PCR（in situ PCR）开展HPV检测，并通过免疫组织化学（immunohistochemistry）法检测p16-INK4A的表达水平。结果显示，189份前列腺癌样本中37份（19.6%）检出高危型人乳头瘤病毒（HR-HPV），而167份良性前列腺增生样本中仅16份（9.6%）检出该病毒（比值比为2.3；95%置信区间为1.2~4.3；P=0.01）。上述数据提示高危型HPV可能在前列腺癌的发生发展中发挥作用。本研究人群中最常见的HPV基因型为52型和58型，检出率分别为33%和17%。所有原位PCR检测HPV阳性的样本均检出挖空细胞，这是HPV感染的特征性病理表现；与HPV阴性样本相比，HPV阳性样本中p16-INK4A呈现过表达状态，间接提示高危型HPV E7癌蛋白的存在。本研究结果表明，HPV感染在前列腺癌的发生中具有重要作用。