RRSS #08: Evaluating Prevalence HPV Infection Among Head and Neck Cancer Patients

RRRSS

• 批准号: 7952659
• 负责人: DENNIS M. DEAPEN
• 金额: $ 13.68万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7952659
• 关键词: RRSS; #08; Evaluating; Prevalence; HPV

Head and neck cancer (HNC) includes malignant tumors arising from a variety of sites in the upper aerodigestive tract (UADT), including the oral cavity, the pharynx, and the larynx. HNC represents the fifth most common malignancy worldwide. It was ranked as the eighth leading cause of cancer death in the world. In 2008, there were an estimated 48,000 new cases and more than 11,000 deaths of HNC in the United States. More than 90% of head and neck malignancies are squamous cell carcinoma (SCC), originating from the epithelium which lines the UADT. The incidence of head and neck squamous cell carcinoma (HNSCC) increases with age and is more common in men than in women. Tobacco and alcohol consumption are well established risk factors for HNSCC. However, a proportion of HNSCC occurs in nonsmokers and nondrinkers, suggesting the presence of other risk factors. Human papilloma virus (HPV) has been proven to be an etiologic factor for cervical cancer. HPV primarily infects the epithelium and induces benign as well as malignant lesions of the mucosa and skin. More than 70 types of HPV have been described. According to their implications in carcinogenesis, particularly the malignant progression of cervical tumors, HPV types were classified into high-risk (16, 18, 31,33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82) and low-risk (6, 11, 26, 40, 42, 53, 54, 55, 57, 66, 83 and 84) groups. Low-risk types are associated with benign lesions such as warts, while infections with high-risk types progress to malignant lesions. High-risk HPV types 16 and 18 have been reported as the most prominent etiologic factors behind the development of cervical cancer. In recent decades, molecular and epidemiologic data have linked HPV with HNSCC. Although HPV type 16 alone was found to account for more than 90% of HPV-positive HNSCC and HPV type 18 is the second most common genotype, a variety of other high- and low-risk HPVs were also found to be present in HNSCC. In fact, the prevalence of other HPV genotypes (other than the 16 and 18) has been significantly underreported, either due to lack of sensitive viral detection methods used, type of specimen tested, and lack of actual testing for these non-HPV16 and non-HPV18 genotypes. Furthermore, the contribution of non-HPV16/18 genotypes as cofactors that participate in the oncogenic process has not been fully examined, nor has it been excluded that different HPV genotypes have different colonization and oncogenic potential in distinct oral tumor sites. Most HPV-associated HNSCC tend to occur in the oropharynx, with highest distribution in the tonsils. The proportion of HNSCC that are potentially HPV-related has been on the rise in the U.S., while the potentially HPV-unrelated HNSCC declined. Presence of HPV in HNSCC has been linked with sexual behaviors. Patients with HPV-positive HNSCC tend to be younger and free of smoking and drinking history, the majority of them are females. They also seem to have a better survival than the HPV-negative HNSCC patients, due to an increased radiocurability of HPV-positive tumors. Evidence supports the idea that HNSCC is a multifactorial disease with at least two, possibly distinct, pathways, one driven by tobacco and alcohol consumption, the other driven by HPV. The reported prevalence of HPV in HNSCC varied between 0-100% . This broad variation in HPV detection rates is attributable to tumor site, HPV detection method (polymerase chain-reaction (PCR), in situ hybridization (ISH), or Southern hybridization), specimen source and collection methods (swabs, brushings, mouthwash, fresh tissue, fixed tissue, etc.), use of HPV type specific vs. universal primers, and sample size and composition. PCR is consider more sensitive than the other testing methods. Small sample size and the inability to classify cases by anatomic subsite and to differentiate primary, recurrent, and metastatic tumors is likely to have contributed to the inconsistencies. The recognition of HPV as a major etiologic agent for HNSCC necessitates a new understanding of the diseases development and stimulates research in order to develop strategies for the screening, education, prevention, diagnosis, and treatment of HNSCC.

头颈癌 (HNC) 包括源自上呼吸消化道 (UADT) 多个部位的恶性肿瘤，包括口腔、咽和喉。 HNC 是全球第五大常见恶性肿瘤。它被列为世界第八大癌症死亡原因。 2008 年，美国估计有 48,000 例新发 HNC 病例，11,000 多人死亡。超过 90% 的头颈部恶性肿瘤是鳞状细胞癌 (SCC)，起源于 UADT 上皮。头颈鳞状细胞癌（HNSCC）的发病率随着年龄的增长而增加，男性比女性更常见。吸烟和饮酒是 HNSCC 的明确危险因素。然而，部分 HNSCC 发生在不吸烟和不饮酒的人群中，这表明存在其他危险因素。 人乳头瘤病毒（HPV）已被证明是宫颈癌的病因。 HPV主要感染上皮并引起粘膜和皮肤的良性和恶性病变。已有 70 多种 HPV 类型被描述。 根据其在致癌作用，特别是宫颈肿瘤恶性进展中的影响，HPV 类型被分为高危型（16、18、31,33、35、39、45、51、52、56、58、59、68、 73 和 82）和低风险（6、11、26、40、42、53、 54、55、57、66、83和84)组。低风险类型与疣等良性病变相关，而高风险类型的感染则进展为恶性病变。据报道，高危 HPV 16 型和 18 型是宫颈癌发展背后最重要的病因。 近几十年来，分子和流行病学数据已将 HPV 与 HNSCC 联系起来。尽管仅 HPV 16 型就占 HPV 阳性 HNSCC 的 90% 以上，并且 HPV 18 型是第二常见的基因型，但还发现多种其他高危和低危 HPV 也存在于 HNSCC 中。事实上，其他 HPV 基因型（16 型和 18 型除外）的流行率被严重低估，原因可能是缺乏敏感的病毒检测方法、检测的样本类型以及缺乏对这些非 HPV16 和非 HPV 基因型的实际检测。 -HPV18基因型。此外，非HPV16/18基因型作为参与致癌过程的辅助因子的贡献尚未得到充分检验，也不排除不同的HPV基因型在不同的口腔肿瘤部位具有不同的定植和致癌潜力。大多数 HPV 相关的 HNSCC 往往发生在口咽部，其中扁桃体的分布最多。在美国，潜在与 HPV 相关的 HNSCC 比例一直在上升，而潜在与 HPV 无关的 HNSCC 则有所下降。 HNSCC 中 HPV 的存在与性行为有关。 HPV阳性的头颈部鳞状细胞癌患者往往年龄较小，无吸烟、饮酒史，以女性为主。由于 HPV 阳性肿瘤的放射治疗能力增强，他们似乎也比 HPV 阴性 HNSCC 患者有更好的生存率。有证据支持 HNSCC 是一种多因素疾病，至少有两种可能截然不同的途径，一种是由吸烟和饮酒引起的，另一种是由 HPV 引起的。 据报道，HNSCC 中 HPV 的患病率在 0-100% 之间变化。 HPV 检测率的这种巨大差异可归因于肿瘤部位、HPV 检测方法（聚合酶链反应 (PCR)、原位杂交 (ISH) 或 Southern 杂交）、样本来源和采集方法（拭子、刷牙、漱口水、新鲜样本）。组织、固定组织等）、HPV 类型特异性引物与通用引物的使用，以及样本大小和组成。 PCR 被认为比其他检测方法更敏感。样本量小以及无法按解剖亚部位对病例进行分类以及区分原发性、复发性和转移性肿瘤可能是造成不一致的原因。 认识到 HPV 是 HNSCC 的主要病因，需要对疾病的发展有新的认识，并刺激研究，以便制定 HNSCC 的筛查、教育、预防、诊断和治疗策略。