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

头颈癌（HNC）包括由上呼吸消化道（UADT）中的多个部位产生的恶性肿瘤，包括口腔、咽和喉。HNC是全球第五大常见恶性肿瘤。它被列为世界上第八大癌症死亡原因。2008年，美国估计有48，000例新病例和11，000多例HNC死亡。超过90%的头颈部恶性肿瘤是鳞状细胞癌（SCC），起源于衬在UADT上的上皮。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，一部分HNSCC发生在非吸烟者和非饮酒者中，这表明存在其他风险因素。 人乳头状瘤病毒（HPV）是宫颈癌的重要致病因子。HPV主要感染上皮细胞，并诱导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。 根据其在致癌作用中的意义，特别是宫颈肿瘤的恶性进展，HPV类型被分为高危型和高危型。（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。低风险类型与良性病变如疣有关，而高风险类型的感染则进展为恶性病变。据报道，高危型HPV 16和18型是宫颈癌发展背后最突出的病因因素。 近几十年来，分子和流行病学数据将HPV与HNSCC联系起来。虽然发现HPV 16型单独占HPV阳性HNSCC的90%以上，HPV 18型是第二常见的基因型，但也发现HNSCC中存在多种其他高风险和低风险HPV。事实上，其他HPV基因型（16和18型除外）的患病率被严重低估，这是由于缺乏敏感的病毒检测方法，测试的标本类型以及缺乏对这些非HPV 16和非HPV 18基因型的实际检测。此外，非HPV 16/18基因型作为参与致癌过程的辅因子的贡献尚未得到充分研究，也没有排除不同的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倾向于发生在口咽部，其中扁桃体的分布最高。在美国，与HPV潜在相关的HNSCC的比例一直在上升，而潜在的HPV无关的HNSCC下降。 HNSCC中HPV的存在与性行为有关。HPV阳性的HNSCC患者多为年轻人，无吸烟、饮酒史，女性居多。由于HPV阳性肿瘤的放射治疗能力增强，他们的生存率似乎也比HPV阴性的HNSCC患者更好。证据支持HNSCC是一种多因素疾病，至少有两种可能不同的途径，一种是由烟草和酒精消费驱动，另一种是由HPV驱动。 HNSCC中HPV的报告患病率为0-100%。HPV检测率的这种广泛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）、标本来源和收集方法（拭子、刷拭、漱口水、新鲜组织、固定组织等），HPV类型特异性引物与通用引物的使用，以及样本量和组成。 PCR被认为比其他检测方法更敏感。小样本量和无法按解剖亚部位分类病例以及区分原发性、复发性和转移性肿瘤可能导致了不一致。 HPV作为HNSCC的主要病原体的认识需要对疾病的发展有新的认识，并刺激研究，以制定HNSCC的筛查，教育，预防，诊断和治疗策略。

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.