Clinical Significance of Different Histology and High-Risk HPV Types in Neuroendocrine Carcinomas of the Cervix

This study aimed to investigate the impact of different histologic and high-risk (HR) human papillomavirus (HPV) types on the clinicopathologic characteristics and survival of patients with neuroendocrine carcinoma of the cervix (NEC). We retrospectively reviewed the medical records of patients with NEC diagnosed and treated at the Seoul National University Hospital between January 2000 and December 2021. Two pathologists specializing in gynecologic oncology thoroughly examined the slides. To determine the type of HPV infection, microarray analysis and next-generation sequencing were conducted. In addition, the impact of several variables on progressoin-free survival (PFS) and overall survival (OS) was investigated. In total, 47 patients with NEC were included in this analysis. Small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC) were identified in 36 (76.6%) and 11 (23.4%) patients, respectively. Whereas 31 (66.0%) patients had a pure NEC, 16 (34.0%) were diagnosed with a mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN). Of the 32 NEC patients whose HPV infection status was confirmed, HR-HPV infection was found in 30 of them (93.8%). Nineteen patients were infected with HPV 18. Between patients infected with HPV 16 or 18 and HR-HPV other than 16 or 18, there was no significant difference in most clinicopathologic characteristics such as histology (P=0.311). However, HR-HPV type other than 16 or 18 was associated with pelvic lymph node metastasis (P=0.044) and advanced stage (P=0.035). In the Kaplan-Meier analysis and the Cox regression analyses, no significant difference in PFS and OS was observed between LCNEC and SCNEC, pure NEC and MiNEN, and HPV 16 or 18 and HR-HPV other than 16 or 18. High-risk HPV infection, especially from HPV 18, might play a role and impact on NEC pathogenesis. In this study, we did not find evidence that diverse histology and HR-HPV types affect PFS and OS.