Wittekindt C, Wagner S, Mayer C S, Klußmann J P
Klinik für HNO-Heilkunde, Kopf-/Halschirurgie, Plastische Operationen, Universitätsklinikum Gießen und Marburg GmbH, Standort Gießen.
Laryngorhinootologie. 2012 Mar;91 Suppl 1:S1-26. doi: 10.1055/s-0031-1297241. Epub 2012 Mar 28.
Head and Neck Squamous Cell Carcinoma (HNSCC) are the 6th most common cancers worldwide. While the incidence of larynx-hypopharynx carcinoma decreases, actually an increase in oropharyngeal squamous cell carcinoma (OSCC) is observed. Classical risk factors for HNSCC are smoking and alcohol. Though, it was shown recently for 25 to 60% of OSCC, to be associated with an infection by oncogenic human papilloma virus (HPV). The development of "common" head-neck-tumors is substantially enhanced by an accumulation of genetic changes, which lead to an inactivation of tumor suppressor genes or to an activation of proto-oncogenes. A more or less uniform sequence of different DNA-damages leads to genetic instability. In this context, an early and frequent event is deletion on the short arm of chromosome 9, which results in inactivation of the p16-gene. On the contrary, for HPV-induced carcinogenesis, expression of the viral proteins E6 and E7 is most important, since E6 and E7 lead to inactivation of the cellular tumor-suppressor-proteins p53 and Rb. The process of natural transoral infection is not yet clear. However, as a matter of fact peroral HPV-infection is not seldom and in most cases such an infection heals completely and uneventfully. Smoking seems to increases the probability for developing an HPV-associated tumor. The association of HNSCC with HPV can be proven with established methods in clinical diagnostics. In addition to classical prognostic factors, diagnosis of an HPV-association may become important for future therapies. Prognostic relevance of HPV probably surmounts many known risk-factors, for instance regional metastasis. Until now, no other molecular markers are established in clinical routine. Future therapy concepts may vary for the two subgroups of patients, especially patients with HPV-associated OSCC may take advantage of a less aggressive postoperative treatment. Finally an outlook will be given on possible target-aimed therapies, of which so far only antibodies against EGF-receptors are established in clinical practice.
头颈部鳞状细胞癌（HNSCC）是全球第六大常见癌症。虽然喉下咽癌的发病率有所下降，但口咽鳞状细胞癌（OSCC）的发病率实际上却在上升。HNSCC的经典风险因素是吸烟和饮酒。不过，最近有研究表明，25%至60%的OSCC与致癌性人乳头瘤病毒（HPV）感染有关。“常见”头颈部肿瘤的发生会因基因变化的积累而显著增强，这些基因变化会导致肿瘤抑制基因失活或原癌基因激活。不同DNA损伤的或多或少一致的序列会导致基因不稳定。在这种情况下，一个早期且常见的事件是9号染色体短臂缺失，这会导致p16基因失活。相反，对于HPV诱导的致癌作用，病毒蛋白E6和E7的表达最为重要，因为E6和E7会导致细胞肿瘤抑制蛋白p53和Rb失活。自然经口感染的过程尚不清楚。然而，事实上经口HPV感染并不少见，而且在大多数情况下，这种感染会完全且顺利地痊愈。吸烟似乎会增加患HPV相关肿瘤的可能性。HNSCC与HPV的关联可以通过临床诊断中的既定方法得到证实。除了经典的预后因素外，HPV关联的诊断对于未来的治疗可能也很重要。HPV的预后相关性可能超过许多已知的风险因素，例如区域转移。到目前为止，临床常规中尚未确立其他分子标志物。未来针对这两个患者亚组的治疗理念可能会有所不同，尤其是HPV相关OSCC患者可能会受益于不太激进的术后治疗。最后，将展望可能的靶向治疗，到目前为止，临床实践中仅确立了针对表皮生长因子受体的抗体。
