HPV, cervical neoplasia, and vaccination

已知HPV是宫颈癌和其他肛门生殖器和头颈部癌症的一个子集的必要原因，包括许多癌症（例如，宫颈癌和肛门癌），在艾滋病毒的背景下升高。 然而，虽然HPV感染是常见的，但癌症的发展是罕见的。 这表明，除了HPV感染外，辅助因子对宫颈癌的发展也很重要。该项目旨在阐明HPV和辅助因子在宫颈癌及其前体病因学中的作用，确定不同组织学形式的宫颈癌的风险因素是否相似或不同，并将所获得的知识应用于新的预防策略。 到目前为止，已经进行了几项研究来实现我们的目标，包括美国宫颈腺癌和鳞状细胞癌的多中心病例对照研究，HPV诱导的低度宫颈病变妇女的纵向研究，以及台湾HPV和宫颈癌的队列研究。 迄今为止，这些研究的结果表明：1）虽然HPV感染是所有组织学类型的宫颈癌发展所必需的，但在癌症中观察到的HPV类型/变体的分布因组织学而异，2）与不同组织学类型的宫颈癌相关的辅助因子不同，而所有组织学形式的宫颈癌均与易患HPV感染的性行为变量相关，宫颈腺癌似乎优先与表明激素参与的风险因素相关，3）免疫相关基因（包括HLA和KIR基因）的多态性与宫颈癌的发展相关，以及4）HPV DNA检测是预防宫颈癌的有用筛查检测。 此外，我们进行了分子流行病学研究，结果表明：1）自然感染产生的抗体可防止HPV再次感染; 2）粘膜免疫标志物在月经周期中各不相同，并受口服避孕药使用的影响，这表明局部免疫及其在HPV持续和进展易感性中的作用的研究需要考虑这些变化。 这项工作是由校内NCI基金赞助的。

HPV is known to be a necessary cause of cervical cancer and a subset of other anogenital and head and neck cancers, including many cancers (e.g., cervical and anal cancers) that are elevated in the context of HIV. However, while HPV infection is common, development of cancer is rare. This suggests that in additional to HPV infection, co-factors are important for the development of cervical cancer. This project aims to elucidate the role of HPV and co-factors in the etiology of cervical cancer and its precursors, to define whether risk factors are similar or different for different histological forms of cervical cancer, and to apply knowledge gained to novel prevention strategies. Several studies have been conducted to date to achieve our goals, including a multicenter case-control study of cervical adenocarcinomas and squamous cell carcinomas in the US, a longitudinal study of women with low-grade, HPV-induced cervical lesions, and a cohort study of HPV and cervical cancer in Taiwan. Results from these studies to date have shown that 1) while HPV infection is required for the development of all histological types of cervical cancer the distribution of HPV types/variants observed in cancers vary by histology, 2) co-factors associated with distinct histological types of cervical cancer differ and while all histological forms of cervical cancer are associated with sexual behavior variables that predispose to HPV infection, cervical adenocarcinomas appear to be preferentially associated with risk factors that indicate hormonal involvement, 3) polymorphisms in immune-related genes (including HLA and KIR genes) are associated with the development of cervical cancer, and 4) HPV DNA testing is a useful screening test for the prevention of cervical cancer. In addition, we have conducted molecular epidemiology studies that have shown that 1) antibodies generated in response to natural infections protect against re-infection with HPV and 2) markers of mucosal immunity vary across the menstrual cycle and are affected by oral contraceptive use, suggesting that studies of local immunity and its role in predisposition to HPV persistence and progression need to account for these changes. This effort is sponsored by Intramural NCI funds.