Wittekindt Claus, Wuerdemann Nora, Gattenlöhner Stefan, Brobeil Alexander, Wierzbicka Malgorzata, Wagner Steffen, Klußmann Jens Peter
Department of Otorhinolaryngology, Head and Neck Surgery, University of Giessen, Klinikstrasse 33, 35392, Giessen, Germany.
Department of Pathology, University of Giessen, Giessen, Germany.
Eur Arch Otorhinolaryngol. 2017 Nov;274(11):3837-3842. doi: 10.1007/s00405-017-4718-1. Epub 2017 Aug 31.
The contribution of human papillomavirus (HPV) to the development and clinical outcome of oropharyngeal cancers has been well documented. The association of HPV in laryngeal squamous cell carcinoma (LSCC) has been examined in several studies, but controversy exists regarding its role in carcinogenesis, the outcome of the patients and thus, clinical significance of HPV testing in LSCC. In this review, we give an update of known associations between HPV-positive testing and carcinogenesis in laryngeal cancer. In an early study, the HPV-DNA detection rate in LSCC was documented being 24.0% with significant regional differences. Non-HPV-16 types were more often detected in LSCC when compared to the oropharynx. Later, single institution case series revealed markedly fewer amounts (<10%) of HPV DNA in LSCC and the results suggested that high-risk HPV infections seem to be biologically irrelevant in most LSCC. The significance of p16INK4a (p16) expression as a surrogate marker towards high-risk HPV infection and the outcome in LSCC is doubtful, since only few p16-positive LSCC samples are HPV RNA positive and accordingly there was poor correlation of p16-test results towards the outcome in LSCC. Recent meta-analysis (n = 2739) and large case series (n = 1042) of LSCC revealed the true rate of HPV-driven LSCC being 8.6%, respectively, <5%. In the latter the rate of DNA-, DNA/RNA-, DNA/p16, and DNA/RNA/p16 positivity was 5.7, 3.1, 1.9, and 1.5%, respectively. These results indicate relevant amounts of insignificant/transient HPV infection in LSCC specimen. However, in the same study the rate of transforming HPV infections increased since 2000, and younger patients had higher amounts of HPV-driven LSCC. Serologic testing of E6/E7 antibodies additionally revealed odds ratios between 2 and 5 as a hint for a weak contribution of high-risk HPV infection and the development of LSCC. The contribution of HPV for the development of LSCC needs future investigations, to date, routine HPV testing of LSCC specimen is not warranted.
人乳头瘤病毒（HPV）对口咽癌发生发展及临床结局的影响已有充分文献记载。多项研究对HPV与喉鳞状细胞癌（LSCC）的关联进行了探究，但关于其在致癌过程中的作用、患者预后以及HPV检测在LSCC中的临床意义仍存在争议。在本综述中，我们更新了HPV检测阳性与喉癌致癌作用之间已知关联的相关内容。在一项早期研究中，LSCC中HPV-DNA的检出率为24.0%，存在显著的地区差异。与口咽癌相比，LSCC中更常检测到非HPV-16型。后来，单机构病例系列研究显示LSCC中HPV DNA的含量明显较少（<10%），结果表明高危HPV感染在大多数LSCC中似乎与生物学无关。p16INK4a（p16）表达作为高危HPV感染替代标志物及LSCC预后的意义存疑，因为仅有少数p16阳性的LSCC样本HPV RNA呈阳性，因此p16检测结果与LSCC预后的相关性较差。近期对LSCC的荟萃分析（n = 2739）和大型病例系列研究（n = 1042）分别显示，HPV驱动的LSCC的实际发生率为8.6%、<5%。在后者中，DNA、DNA/RNA、DNA/p16和DNA/RNA/p16阳性率分别为5.7%、3.1%、1.9%和1.5%。这些结果表明LSCC标本中存在一定数量无意义/短暂的HPV感染。然而，在同一研究中，自2000年以来，具有转化能力的HPV感染率有所上升，且年轻患者中HPV驱动的LSCC数量更多。E6/E7抗体的血清学检测还显示，比值比在2至5之间，提示高危HPV感染与LSCC发生之间的作用较弱。HPV对LSCC发生的作用仍需未来进一步研究，目前，对LSCC标本进行常规HPV检测并无必要。
