Abstract:
Introduction: Cervical cancer is the second most common cancer in Indian women, constituting 22.86% of all female malignancies. Neuroendocrine carcinoma (NEC) is a rare subtype of cervical cancer, accounting for approximately 1.4% of all cervical malignancies. These tumors are biologically aggressive and portend a poorer prognosis compared to the more common squamous cell carcinoma. Accurate diagnosis is critical due to their aggressive course and limited therapeutic window. Despite their clinical significance, literature on cervical NEC remains sparse, with most reports limited to isolated cases or small series.
Aims and Objectives: This study presents a comprehensive 5-year clinicopathological, immunohistochemical, and HPV-based analysis from a tertiary cancer center in India to evaluate prognostic markers and survival correlations.
Material and Methods: A retrospective study was conducted on 47 patients with cervical NEC diagnosed between 2019 and 2023. Data on clinical features, histology, immunohistochemistry (IHC), HPV subtypes, treatment, and outcomes were collected. Kaplan–Meier survival curves and Cox proportional hazard models were used to identify significant predictors of overall survival (OS) and disease-free survival (DFS).
Results: Among 47 patients with cervical neuroendocrine carcinoma (NEC), the median age was 48 years (range: 37–57). Histologic subtypes included small-cell NEC (60%), large-cell NEC (26%), and mixed/other variants (15%). The median tumor size was 4.5 cm. At diagnosis, pelvic lymph node metastases were present in 40%, with additional metastases to the lung (15%), liver (10%), and bone (8%). Immunohistochemically, synaptophysin was positive in 90%, INSM1 in 75%, and chromogranin was negative in 65% of cases. TTF-1 was absent in 80%, and a high Ki-67 index (>90%) was seen in 70%, indicating strong proliferative activity. Recurrence occurred in 68% of patients, with a median time to recurrence of 6 months, most commonly involving pelvic nodes (50%) and distant organs (30%). Kaplan–Meier analysis showed a median overall survival (OS) of 15 months (95% CI: 12–18) and median disease-free survival (DFS) of 8 months (95% CI: 6–10). HPV subtyping revealed HPV-16 as the most prevalent (56%) and strongly associated with better outcomes (median OS: 32 months, DFS: 22 months), while HPV-18 and HPV-negative tumors showed poorer survival (median OS: 24 months, DFS: 16 months). These differences were statistically significant (OS: p=0.01; DFS: p=0.02).
Conclusions: This study represents one of the largest recent single-institution cohorts on cervical neuroendocrine carcinoma (NEC) in India. Cervical NECs demonstrate aggressive clinical behavior with early recurrence and limited survival. Tumor size and a high Ki-67 index (>90%) are key independent predictors of poor prognosis, while HPV-16 positivity is associated with improved outcomes. Traditional neuroendocrine markers such as Synaptophysin and INSM1 were not independently prognostic. These findings highlight the importance of early diagnosis, HPV subtyping, and risk-adapted multimodal treatment, particularly for high-risk HPV-18 and highly proliferative tumors.
Keywords: Cervical neuroendocrine carcinoma; Ki-67; HPV-16; HPV-18; Synaptophysin; INSM1; Immunohistochemistry; Prognosis; Recurrence; Survival analysis; India.
