Department of Surgery, Institut Curie, 92210, St Cloud, France.
Institut Curie, Inserm U900 - Bioinformatics, biostatistics, epidemiology and computational systems. Cancer biology, 35, rue Dailly, 92210, Saint-Cloud, France.
BMC Cancer. 2019 Apr 23;19(1):375. doi: 10.1186/s12885-019-5582-8.
Most endocervical adenocarcinomas are human papillomavirus (HPV)-related cancers associated with p16 immunostaining. Ovarian metastasis from cervical cancer is a rare phenomenon, the mechanism of dissemination remains unclear. The diagnosis of metastasis may be difficult to establish when the ovarian neoplasm presents features consistent with primary tumor. Immunohistochemical expression of p16 in ovarian tumors can guide the diagnosis of metastasis from HPV-related cervical cancer, but p16 positivity is nonspecific. Identical HPV genotype in the paired endocervical and ovarian tumors is a better marker for cervical origin, which may also be confirmed by identical HPV integration site.
Two women presented with HPV18 cervical adenocarcinoma. No signs of disease were visible on MRI after treatment. After several years of follow-up, mucinous ovarian tumors were discovered in both patients. Molecular analyses showed that the ovarian lesions were HPV18-positive; indicating a primary cervical origin. A third woman was diagnosed with grade 1 ovarian endometrioid carcinoma with no peritoneal carcinomatosis. Final histological examination and HPV genotyping revealed HPV18-related in situ endometrioid adenocarcinoma in the endocervix and HPV18-related invasive endometrioid adenocarcinoma in the endometrium and both ovaries. Additional molecular analyses performed in two patients identified the same HPV integration sites in both the ovarian and cervical tumors, confirming that the ovarian mass was a metastasis from the cervical adenocarcinoma.
We report three new cases of ovarian neoplasia in which the diagnosis of metastasis from cervical cancer was supported by the same HPV genotype and the same integration site in the paired cervical and ovarian tumors. To our knowledge, this is the first report of molecular evidence of the cervical origin of an ovarian metastasis. HPV screening should be performed in ovarian tumors for all patients with history of cervical neoplasia.
大多数宫颈腺癌是与 p16 免疫染色相关的人乳头瘤病毒 (HPV) 相关癌症。宫颈癌的卵巢转移是一种罕见现象，其传播机制尚不清楚。当卵巢肿瘤的特征与原发性肿瘤一致时，转移的诊断可能难以确立。卵巢肿瘤中 p16 的免疫组织化学表达可指导 HPV 相关宫颈癌转移的诊断，但 p16 阳性并非特异性。配对的宫颈和卵巢肿瘤中相同的 HPV 基因型是宫颈来源的更好标志物，也可通过相同的 HPV 整合部位来证实。
两名女性患有 HPV18 宫颈腺癌。治疗后 MRI 未见疾病迹象。经过几年的随访，两名患者均发现黏液性卵巢肿瘤。分子分析显示卵巢病变 HPV18 阳性；表明宫颈原发。第三名女性被诊断为 1 级卵巢子宫内膜样癌，无腹膜癌。最终的组织学检查和 HPV 基因分型显示，宫颈内有 HPV18 相关原位子宫内膜样腺癌，子宫内膜和两个卵巢均有 HPV18 相关浸润性子宫内膜样腺癌。对两名患者进行的其他分子分析显示，卵巢和宫颈肿瘤中存在相同的 HPV 整合部位，证实卵巢肿块是宫颈腺癌的转移。
我们报告了三例新的卵巢肿瘤病例，这些病例的宫颈癌转移诊断得到了配对的宫颈和卵巢肿瘤中相同的 HPV 基因型和相同的整合部位的支持。据我们所知，这是首次报道卵巢转移来自宫颈的分子证据。所有有宫颈肿瘤病史的患者都应进行 HPV 筛查。
