HPV DNA integration site as proof of the origin of ovarian metastasis from endocervical adenocarcinoma: three case reports

Alexandra Arfi 1 Delphine Hequet 1, 2 Guillaume Bataillon 3 Carine Tran-Perennou 3 Fereshteh Farkhondeh 3 Xavier Sastre-Garau 4 Virginie Fourchotte 1 Roman Rouzier 1, 2 Enora Laas 1 Nicolas Pouget 1 Anne Vincent-Salomon 3 Emmanuelle Jeannot 3, *
* Corresponding author
1 Department of Surgery [Saint-Cloud]
2 Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
3 Department of Pathology [Paris]
4 Department of Pathology [Vandoeuvre-Lès-Nancy]
Abstract : BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSION: 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.
Keywords : p16 Cervical neoplasia HPV Integration Ovarian metastasis
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Alexandra Arfi, Delphine Hequet, Guillaume Bataillon, Carine Tran-Perennou, Fereshteh Farkhondeh, et al.. HPV DNA integration site as proof of the origin of ovarian metastasis from endocervical adenocarcinoma: three case reports. BMC Cancer, BioMed Central, 2019, 19 (1), pp.375. ⟨10.1186/s12885-019-5582-8⟩. ⟨inserm-02297426⟩

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