HPV18-positive Small Cell Neuroendocrine Carcinoma of the Uterine Cervix Treated With Immunotherapy: A Case Report
Sakiko Masumoto1, Masaaki Tanaka2, Kenta Yamamoto2
1Department of Obstetrics and Gynecology, Fukui Prefectural Hospital, Fukui, Japan; s-masumoto-90@pref.fukui.lg.jp.
Background:
Small cell neuroendocrine carcinoma of the cervix (SCNEC) has an extremely poor prognosis. We report a case of recurrent SCNEC with CD274 [Programmed Death-Ligand 1 (PD-L1)] gene amplification and HPV18 positivity, which showed a favorable response to the immune checkpoint inhibitor (ICI) nivolumab.
Case Report:
A 42-year-old woman presented with a lower abdominal mass and was referred to our department. Imaging revealed a uterine cervical tumor with multiple enlarged pelvic lymph nodes. Biopsy confirmed HPV18-positive SCNEC. After one cycle of neoadjuvant chemotherapy, surgery was performed, revealing stage IIIC2p (ypT1b1, ypN1, M0) SCNEC with regional lymph-node invasion, followed by adjuvant chemotherapy. Two months later, enlargement of the para-aortic and left pelvic lymph nodes was detected. Concurrent chemoradiotherapy (CCRT) was administered, resulting in a reduction of lymphadenopathy. Seven months later, an enlarged right supraclavicular lymph node was detected. Nivolumab therapy was initiated because CD274 (PD-L1) gene amplification was detected in tumor tissue. The lymph node decreased in size, and no signs of relapse had been observed for more than three years.
Conclusion:
Comprehensive multimodal therapy, including standard surgery, neoadjuvant and adjuvant chemotherapy, chemoradiation for recurrent lymph nodes, and immune checkpoint inhibition, can achieve a remarkable response in advanced SCNEC harboring CD274 (PD-L1) amplification and HPV18 infection.
Insights
Recurrent small cell neuroendocrine carcinoma of the cervix (SCNEC) with PD-L1 gene amplification responded well to nivolumab. This case highlights the potential of immune checkpoint inhibitors in advanced SCNEC.
Area of Science:
- Gynecologic Oncology
- Immunotherapy
- Molecular Pathology
Background:
- Small cell neuroendocrine carcinoma of the cervix (SCNEC) is a rare and aggressive malignancy with a poor prognosis.
- Human Papillomavirus (HPV) type 18 infection is frequently associated with SCNEC.
- Programmed Death-Ligand 1 (PD-L1) expression and gene amplification are emerging biomarkers in various cancers.
Purpose of the Study:
- To report a case of recurrent, advanced SCNEC with HPV18 positivity and CD274 (PD-L1) gene amplification.
- To evaluate the efficacy of nivolumab, an immune checkpoint inhibitor (ICI), in this specific patient subgroup.
- To emphasize the role of comprehensive multimodal therapy in managing advanced SCNEC.
Main Methods:
- A 42-year-old patient with HPV18-positive SCNEC underwent neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy.
- Recurrent disease led to concurrent chemoradiotherapy (CCRT).
- Subsequent detection of CD274 (PD-L1) gene amplification prompted initiation of nivolumab therapy.
Main Results:
- The patient achieved a favorable response to nivolumab therapy, with significant reduction in lymphadenopathy.
- No signs of relapse were observed for over three years post-treatment.
- The multimodal approach, including ICI, demonstrated remarkable efficacy.
Conclusions:
- Comprehensive treatment strategies, including surgery, chemotherapy, chemoradiation, and immunotherapy, can yield significant benefits in advanced SCNEC.
- CD274 (PD-L1) gene amplification may predict response to ICI in HPV18-positive SCNEC.
- Immune checkpoint inhibition represents a promising therapeutic option for recurrent and advanced SCNEC.
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