Co-expression of SOX2 and HR-HPV RISH predicts poor prognosis in small cell neuroendocrine carcinoma of the uterine cervix

Abstract

Background Small cell neuroendocrine carcinoma of the uterine cervix (SCNEC) is a rare cancer involving the human papilloma virus (HPV), and has few available treatments. The present work aimed to assess the feasibility of SOX2 and HPV statuses as predictive indicators of SCNEC prognosis. Methods The associations of SOX2 and/or high-risk (HR)-HPV RNA in situ hybridization (RISH) levels with clinicopathological characteristics and prognostic outcomes for 88 neuroendocrine carcinoma (NEC) cases were analyzed. Results Among these patients with SCNEC, SOX2, P16INK4A and HR-HPV RISH expression and SOX2/HR-HPV RISH co-expression were detected in 68(77.3%), 76(86.4%), 73(83.0%), and 48(54.5%), respectively. SOX2-positive and HR-HPV RISH-positive SCNEC cases were associated with poorer overall survival (OS, P = 0.0170, P = 0.0451) and disease-free survival (DFS, P = 0.0334, P = 0.0309) compared with those expressing low SOX2 and negative HR-HPV RISH. Alternatively, univariate analysis revealed that SOX2 and HR-HPV RISH expression, either separately or in combination, predicted the poor prognosis of SCNEC patients. Multivariate analysis revealed that the co-expression of SOX2 with HR-HPV RISH may be an independent factor of OS [hazard ratio = 3.597; 95% confidence interval (CI): 1.085–11.928; P = 0.036] and DFS [hazard ratio = 2.880; 95% CI: 1.199–6.919; P = 0.018] prediction in SCNEC. Conclusions Overall, the results of the present study suggest that the co-expression of SOX2 with HR-HPV RISH in SCNEC may represent a specific subgroup exhibiting remarkably poorer prognostic outcomes compared with the expression of any one marker alone.

Positive clinical outcomes following therapy with programmed cell death protein 1/programmed cell death ligand 1 inhibitors in neuroendocrine carcinoma of the cervix

“…NECC has been suggested in numerous studies as a possible HPV-related cancer as well. HPV can be found in virtually all cases of NECs ( Kuji et al, 2017 ; Zhang et al, 2021 ). Castle et al (2018) conducted a meta-analysis of the prevalence of any HPV type detected in 403 SCNEC and 45 LCNEC cases.…”

“…For locally advanced and metastatic disease, various strategies can be applied, including concurrent chemoradiation and brachytherapy with or without adjuvant chemotherapy, neoadjuvant chemotherapy followed by concurrent chemoradiation and brachytherapy, individualized external exposure combined with other treatments, systemic therapy, palliative support therapy, and pelvic exenteration. For patients with multiple recurrences of NECC, targeted therapy combined with chemotherapy may also play a beneficial role, which requires additional evidence for confirmation ( NCCN Guidelines 2022 ; Zhang et al, 2021 ; Chen, J et al, 2021 ; Frumovitz et al, 2017 ; Gadducci et al, 2017 ; Burzawa et al, 2015 ).…”