子宫颈神经内分泌癌HPV基因型及其与临床病理的关系

HPV Genotype of Cervical Neuroendocrine Carcinoma and its Relationship with Clinicopathology

目的 探讨单纯性子宫颈神经内分泌癌(NECC)中高危人乳头瘤病毒(HPV)感染率和HPV基因型分布特点,评价HPV基因型与NECC临床病理特征的相关性,从而为评估HPV疫苗对NECC预防提供理论基础。方法 收集我院2009年4月至2020年12月诊断的59例NECC病例,进行免疫组织化学和DNA人乳头瘤病毒基因分型(23型)检测,分析临床特点、HPV感染情况及两者的关系。结果 患者年龄25~67岁,FIGO分期为Ⅰ期38例(64.4%),Ⅱ期13例(22.0%),Ⅲ期8例(13.6%),IV期0例。组织学类型分布为大细胞NECC 4例、小细胞NECC 54例、大细胞与小细胞神经内分泌混合癌1例。免疫组化结果为所有病例中均至少表达CD56、CgA、Syn和NSE中的两个标记,且都不表达P40、P63、CK5/6,有57/59的病例(96.6%)强阳性表达P16。HPV感染情况为59例患者中57例(96.6%)检测到HPV DNA。在57例HPV阳性病例中,49例(83.1%)感染1种HPV型,8例(13.6%)感染2或3种HPV型,且全部为高危型HPV病例。其中感染HPV16和(或)18的病例总数为53例(89.8%),单独HPV16感染12例(20.3%),多重HPV16感染7例(11.9%),单独HPV18感染33例(55.9%),多重HPV18感染7例(11.9%)。除了感染HPV16/18的病例,另有单独HPV52感染1例(1.7%),单独HPV58感染3例(5.1%)。NECC组织学类型和HPV单纯、多重感染例数无明显相关性(P=0.066)。年龄是否大于43(P=0.319)、NECC组织学类型(P=1.000)、有无淋巴结转移(P=0.208)及FIGO分期(P=1.000)与是否有HPV16/18感染无明显相关性。结论 高危型HPV尤其是HPV16和HPV18,导致了很大比例的NECC,接种HPV16和HPV18疫苗可能会预防大部分NECC的发生。

Objective To investigate infection rates of high-risk human papillomavirus(HPV) and distribution characteristics of HPV genotypes in simple neuroendocrine cervical carcinoma(NECC),and to evaluate correlation between HPV genotypes and clinicopathological features of NECC,so as to provide a theoretical basis for evaluating prevention of NECC by HPV vaccine.Methods From April 2009 to December 2020,59 cases of simple cervical NECC diagnosed in our hospital were collected. Immunohistochemistry and DNA human papillomavirus genotyping(type 23) were detected. Clinical characteristics, HPV infection and relationship were analyzed.Results Age of patients was 25~67 years old. FIGO stages were stage Ⅰ in 38 cases(64.4%),stage Ⅱ in 13 cases(22.0%),stage Ⅲ in 8 cases(13.6%) and stage IV in 0 cases. Pathological types were 4 cases of large cell neuroendocrine carcinoma, 54 cases of small cell neuroendocrine carcinoma and 1 case of mixed large cell and small cell neuroendocrine carcinoma. Immunohistochemical results showed that at least two markers of CD56,CgA,Syn and NSE were expressed in all cases. P40,P63 and CK5/6 were not expressed. P16 was strongly positive in 57/59 cases(96.6%). HPV DNA was detected in 57 of 59 patients(96.6%). Among 57 HPV positive cases, 49 cases(83.1%) were infected with one HPV type, 8 cases(13.6%) were infected with two or three HPV types, and all of them were high-risk HPV cases. Total number of cases infected with HPV16 and/or 18 was 53(89.8%),12 cases of single HPV16 infection(20.3%),7 cases of multiple HPV16 infection(11.9%),33 cases of single HPV18 infection(55.9%),and 7 cases of multiple HPV18 infection(11.9%). In addition to cases of HPV16/18 infection, there were 1 case of HPV52 infection alone(1.7%) and 3 cases of HPV58 infection alone(5.1%). These was no significant correlation between the histological type of NECC and the number of simple or multiple cases of HPV infection(P=0.066).Age greater than 43(P=0.319),histological type of NECC(P=1.000),lymph node metastasis(P=0.208) and FIGO stage(P=1.000) were not significantly correlated with HPV16/18 infection. Conclusion High risk HPV,especially HPV16 and HPV18,could lead to a large proportion of NECC. Vaccination with HPV16 and HPV18 vaccine may prevent most of NECC.