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

头颈部癌(HNC)包括发生在上呼吸道(UADT)各种部位的恶性肿瘤，包括口腔、咽和喉部。HNC是全球第五大最常见的恶性肿瘤。它被列为世界第八大癌症死亡原因。2008年，美国估计有48,000例新的HNC病例和11,000多例死亡。超过90%的头颈部恶性肿瘤是鳞状细胞癌(SCC)，起源于沿UADT排列的上皮。头颈部鳞状细胞癌(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的公认危险因素。然而，HNSCC的一部分发生在不吸烟和不饮酒的人中，这表明存在其他危险因素。 人乳头瘤病毒(HPV)已被证实是宫颈癌的病因之一。HPV主要感染上皮细胞，导致粘膜和皮肤的良性和恶性病变。已经描述了70多种类型的HPV。根据HPV在癌变过程中的作用，特别是宫颈肿瘤的恶性进展，将HPV分型分为高危组(16、18、31、33、35、39、45、51、52、56、58、59、68、73和82)和低危组(6、11、26、40、42、53、54、55、57、66、83和84)。低风险类型的感染与疣等良性病变有关，而高风险类型的感染会进展为恶性病变。高危HPV16型和18型已被报道为宫颈癌发生背后最显著的病因。 近几十年来，分子和流行病学数据将HPV与HNSCC联系在一起。虽然在HPV阳性的HNSCC中，HPV16型占90%以上，HPV18型是第二常见的基因型别，但HNSCC中还存在多种其他高危和低危HPV。事实上，由于缺乏灵敏的病毒检测方法、检测的样本类型，以及缺乏对这些非HPV16和非HPV18基因类型的实际检测，其他HPV基因类型(除16和18外)的流行率一直被严重低估。此外，非HPV16/18基因作为参与致癌过程的辅助因子的作用还没有得到充分的研究，也没有排除不同的HPV基因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相关性HNSCC倾向于发生在口咽部，以扁桃体分布最多。在美国，可能与HPV相关的HNSCC的比例一直在上升，而可能与HPV无关的HNSCC的比例下降。 HPV在HNSCC中的存在与性行为有关。HPV阳性的HNSCC患者往往较年轻，且无吸烟和饮酒史，其中大部分为女性。他们似乎比HPV阴性的HNSCC患者有更好的存活率，这是由于HPV阳性肿瘤的放射治疗能力增加。有证据支持这样一种观点，即HNSCC是一种多因素疾病，至少有两条可能是不同的途径，一条由烟酒消费驱动，另一条由HPV驱动。 报告的HPV在HNSCC中的患病率在0-100%之间。HPV检测率的巨大差异是由于肿瘤部位、HPV检测方法(聚合酶链式反应(PCR)、原位杂交(ISH)或Southern杂交)、标本来源和采集方法(拭子、刷子、漱口水、新鲜组织、固定组织等)、HPV型特异性与通用引物的使用，以及样本大小和组成。聚合酶链式反应被认为比其他检测方法更敏感。样本量小和不能根据解剖部位对病例进行分类和区分原发、复发和转移肿瘤可能是导致不一致的原因。 认识到HPV是HNSCC的主要病因，需要对疾病的发展有新的认识，并促进研究，以便为HNSCC的筛查、教育、预防、诊断和治疗制定策略。

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.