Neuroendocrine carcinomas of the cervix account for less than 2% of all invasive cervical cancers and are classified as low-grade (carcinoid, atypical carcinoid tumor) or high-grade (known as small- and large-cell) neuroendocrine carcinomas. There are increasing data showing that cervical neuroendocrine carcinomas may be associated with the human papillomavirus (HPV), especially HPV18, and most will stain positive for p16. Immunohistochemistry markers such as synaptophysin and CD56 are the most sensitive markers. Although there are no commonly associated mutations, PIK3CA, KRAS, and TP53 are the most frequently found mutations in neuroendocrine tumors. Neuroendocrine cervical carcinomas are exceedingly aggressive tumors with a high tendency for nodal involvement and distant metastases. Age, lymph node metastases, smoking, pure small-cell histology, and tumor size are independent prognostic factors. Overall, the 5-year survival rate is 36% and the median overall survival ranges between 22 and 25 months. Treatment options are often extrapolated from small-cell lung cancer and limited retrospective studies. The preferred treatment is a multimodal approach of surgery, chemoradiation, and systemic chemotherapy. The most common chemotherapy regimen used as initial therapy is a combination of cisplatin and etoposide. In the setting of recurrent disease, a combination of topotecan, paclitaxel, and bevacizumab has demonstrated favorable outcomes. Multicenter tumor registries, such as the Neuroendocrine Cervical Tumor Registry (NeCTuR), are an opportunity to evaluate patterns of disease treatment and oncologic outcomes.
- cervical cancer
- uterine cervical neoplasms
- neuroendocrine tumors
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Contributors GS: wrote the manuscript, tables, and figures. NG: reviewed the manuscript; provided information on status of NeCTuR database. MF: reviewed, corrected, and medically edited all the manuscript content. AG: reviewed, corrected the manuscript and Figure 1; edited all the chemotherapy information in the manuscript. All authors made substantial contributions to the study conception and design, and/or acquisition of articles for inclusion in the revision. All authors approved the final version of the manuscript prior to submission. Study conception and design: GS and MF. Acquisition of articles to include: NG, GS, MF, and AG. Analysis and interpretation of articles: GS, MF, and AG. Drafting of manuscript: GS, MF, and AG. Critical revision: GS and MF.
Funding This study has been funded by a generous donation from the Allyson Whitney Foundation.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Commissioned; internally peer reviewed.
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