Neuroendocrine Carcinoma of the Cervix: Clinicopathologic Study and Review of the Literature

BackgroundNeuroendocrine carcinoma of the cervix (CNECC) is a rare variant of cervical cancer. The prognosis of women with CNECC is poor and there is no standardized therapy for this type of malignancy. To discuss the clinical and pathological features and prognosis of CNECC.MethodsTwenty one patients diagnosed as CNECC of cervix from May 2008 to September 2021 were retrospectively analyzed at Peking University people's hospital, were analyzed retrospectively including hematoxylin-eosinstaining （HE）slides review, immunohistochemistry results,Thinprep cytology test(TCT) and human papillomavirus (HPV) Hybrid Capture 2(HC2) assay. and their data were analyzed retrospectively. Telephone and medical records were followed up for 3-160 months with an average follow-up time of 49.8 month.ResultsThe patient's average age was 48.6 years old (range: 33–69 years). The first symptoms of 11 cases had vaginal bleeding, 2 cases had vaginal discharge, and the others were asymptomatic. Among the 21 patients, 17 cases were diagnosed as neuroendocrine carcinoma by biopsy. There were 9 cases with TCT examination and HC2 tests before biopsy, TCT results of 4 cases were positive. High-risk HPV of 7 cases were positive. The morphology of cancer cells were relatively consistent, the cytoplasm was sparse, the nuclei were obviously blue stained, and accompanied by extensive neoplastic necrosis. 13 cases were pure CNECC(61.9%), 8 cases were mix types of CNECC(38.1%).There were 3 cases accompanied by squamous cell carcinoma,5 cases accompanied by adenocarcinoma.The positive detection rate of Syn, CgA, CD56,p16 and TTF1 were 85.7%(18/21), 42.9%(9/21), 85.7% (18/21), 81%(17/21) 52.4%(11/21),respectively.The overall survival rate of 21 NECC cases was 71.4%(15/21).ConclusionsCNECC was a extremely rare primary tumor.The tumor was associated with HPV infection. Combined examination of TCT and HPV could significantly improve the detection rate of neuroendocrine carcinoma before biopsy.Pthology diagnosis was based on histological and immunohistochemical examination. It was considered to be highly aggressive malignancy with very poor prognosis.

Hybrid capture 2 and cobas® 4800: Comparison of performance of two clinically validated tests for human papillomavirus primary screening of cervical cancer

Objective To compare, in a primary human papillomavirus screening setting, two different validated human papillomavirus tests, considering their analytical and clinical screening performances. Methods In Tuscany, a human papillomavirus screening program was implemented in 2013. Hybrid capture 2 (Qiagen) was used for testing until May 2016, when it was replaced by the cobas® 4800 human papillomavirus test (Cobas; Roche). We evaluated the performance of Hybrid capture 2 and Cobas on: the same screening population in two different periods (before and after changing to Cobas); the same Hybrid capture 2-positive consecutive samples. Discordant samples (Hybrid capture 2-positive/Cobas negative) were typed on the L1 gene (reverse line blot, AB Analitica) and E6/E7 genes (BD Onclarity assay). Results In the considered time period ( n = 37,775), human papillomavirus positivity was 9.8% and 7.4%, respectively, for Hybrid capture 2 and Cobas ( p < 0.0001). At immediate colposcopy, the cervical intraepithelial neoplasia, grade 2 positive predictive value was, respectively, 23.8% and 34% ( p < 0.001). At one-year recall, human papillomavirus persistence was, respectively, 40.6% and 62.2% ( p < 0.0001). Of Hybrid capture 2-positive re-tested samples ( n = 620), 32.4% were Cobas negative. Of discordant samples typed on L1, 7% were positive for the 12 high-risk human papillomavirus. Of the samples found to be negative for the 12 high-risk human papillomavirus types on L1, 14.5% were positive on E6/E7 typing. Among the discordant samples, the only two cervical intraepithelial neoplasia (CIN) grade 3 lesions were non-high-risk human papillomavirus positive on both L1 and E6/E7 typing. Conclusion At baseline, Hybrid capture 2 showed greater human papillomavirus positivity and a lower CIN2+ positive predictive value than Cobas, which was more specific than Hybrid capture 2 in detection of high-risk human papillomavirus: 80% of discordant samples were confirmed as high-risk human papillomavirus negative. This higher analytical specificity determined the non-identification of two CIN3 lesions.

High-risk Human Papillomavirus Testing for Triage of Women with Previous Cytological Abnormalities from the Vale do Ribeira Region

Objective To evaluate the performance of the hybrid capture 2 (HC2) high-risk papillomavirus (hrHPV) assay and cytological test in women with previous abnormalities, to detect cervical intraepithelial neoplasia grade 2 or worse (≥ CIN 2). Methods A cytological test and HC2 (Qiagen, Gaithersburg, Maryland, EUA) for hrHPV were conducted in 359 liquid-based (Sure Path, Becton Dickinson, TriPath Imaging, Burlington, NC, USA) samples collected from women from the Vale do Ribeira Region, during July 2013 and September 2015 with previous cytology classified as atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (ASC-H), and atypical glandular cells (AGC). The histopathological examination was conducted in 179 women. The performance evaluations were calculated using the “exact” Clopper-Pearson 95% confidence interval (CI) test by MEDCALC (Medcalc Software Ltd, Ostend, Belgium). Results The ≥ CIN 2 frequency was 11.7% (21/179). The HC2 for hrHPV and repeat cytology to detect ≥ CIN 2 obtained, respectively, a sensitivity of 90.5% (95%CI = 69.6–98.8) and 90.5%, (95%CI = 69.6–98.8), a specificity of 65.8% (95% CI = 57.9–73.2) and 43.7% (95%CI = 35.8–51.8), a positive predictive value of 26.0% (95% CI = 21.4–31.3) and 17.6%, (95%CI = 14.9–20.6), and a negative predictive value of 98.1% (95%CI = 93.3–99.5) and 97.2% (95% CI = 90.1–99.2). Conclusion Hybrid capture 2 for hrHPV improves the performance of the detection of ≥ CIN 2, without compromising sensitivity, and provides a greater safety margin to return to the triennial screening of women undergoing follow-up due to previous abnormalities, without underlying ≥ CIN 2.