Cervical cancer encompasses several histologic types, of which the most common is squamous cell (70 percent) (table 1) [1,2]. Adenocarcinoma and its variants account for about 25 percent of cases, while other histologic subtypes are uncommon. Cervical neuroendocrine (mainly small cell) tumors represent only about 2 percent of all cervical malignancies [3-7]. Small cell neuroendocrine carcinoma represents an extrapulmonary variant of small cell lung cancer. (See "Neuroendocrine cancer of unknown primary site" and "Extrapulmonary small cell cancer".)
This topic review will cover the epidemiology, clinical presentation, staging, and treatment of small cell neuroendocrine carcinoma of the cervix. Because of the rarity of other neuroendocrine tumors of the cervix, they will not be discussed further.
The management of squamous cell cervical cancer and adenocarcinoma arising in the uterine cervix, as well as the management of other extrapulmonary sites of small cell cancer, are addressed elsewhere. (See "Management of early stage cervical cancer" and "Management of locally advanced cervical cancer" and "Invasive cervical adenocarcinoma" and "Extrapulmonary small cell cancer".)
EPIDEMIOLOGY AND RISK FACTORS
Small cell neuroendocrine carcinoma of the cervix is a rare disease, accounting for only up to 2 percent of all invasive cervical cancers [3-8]. In a series from the Surveillance, Epidemiology and End Results (SEER) database, the mean annual incidence in the United States from 1977 to 2003 was 0.06 per 100,000 women, compared with 6.6 and 1.2 for squamous cell carcinoma and adenocarcinoma, respectively . Although the disease has been described in women from 22 to 87 years of age, the mean age at diagnosis of small cell neuroendocrine carcinoma of the cervix is about 45 years [10,11]. An association with high risk human papillomavirus (HPV) infection (HPV 18 more than HPV 16) has been described for both small and large cell neuroendocrine cancers [11-15].
In contrast to small cell carcinoma of the lung, smoking has not been established as a risk factor for small cell carcinoma of the cervix. However, it has been associated with a poorer prognosis . (See "Overview of the risk factors, pathology, and clinical manifestations of lung cancer", section on 'Smoking' and "Pathobiology and staging of small cell carcinoma of the lung", section on 'Epidemiology'.)