Pelvic and Ovarian Recurrence of Small HPV-associated Cervical Adenocarcinoma With Transformation to Neuroendocrine Carcinoma

Abu-Sinn, Duaa; Jamison, Jackie; Evans, Matthew C.; McCluggage, W. Glenn

doi:10.1097/pgp.0000000000000749

Cited by 3 publications

(3 citation statements)

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“…It has been reported that lung adenocarcinoma and bladder adenocarcinoma transdifferentiated to SCLC and SCBC due to treatment pressure [62,63]. In cervical cancer, the development of neuroendocrine carcinoma from small HPV-associated AdCC has recently been reported [64]. Although the mixed adenocarcinoma component is the common pattern in mixed SCCC, the origin of SCCC, whether derived from adenocarcinoma or reserve cells of the cervix, remains to be validated.…”

Section: Discussionmentioning

confidence: 99%

Multiomics sequencing and immune microenvironment characteristics define three subtypes of small cell neuroendocrine carcinoma of the cervix

Pan,

Yan,

Yuan

et al. 2024

The Journal of Pathology

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Small cell cervical carcinoma (SCCC) is the most common neuroendocrine tumor in the female genital tract, with an unfavorable prognosis and lacking an evidence‐based therapeutic approach. Until now, the distinct subtypes and immune characteristics of SCCC combined with genome and transcriptome have not been described. We performed genomic (n = 18), HPV integration (n = 18), and transcriptomic sequencing (n = 19) of SCCC samples. We assessed differences in immune characteristics between SCCC and conventional cervical cancer, and other small cell neuroendocrine carcinomas, through bioinformatics analysis and immunohistochemical assays. We stratified SCCC patients through non‐negative matrix factorization and described the characteristics of these distinct types. We further validated it using multiplex immunofluorescence (n = 77) and investigated its clinical prognostic effect. We confirmed a high frequency of PIK3CA and TP53 alterations and HPV18 integrations in SCCC. SCCC and other small cell carcinoma had similar expression signatures and immune cell infiltration patterns. Comparing patients with SCCC to those with conventional cervical cancer, the former presented immune excluded or ‘desert’ infiltration. The number of CD8+ cells in the invasion margin of SCCC patients predicted favorable clinical outcomes. We identified three transcriptome subtypes: an inflamed phenotype with high‐level expression of genes related to the MHC‐II complex (CD74) and IFN‐α/β (SCCC‐I), and two neuroendocrine subtypes with high‐level expression of ASCL1 or NEUROD1, respectively. Combined with multiple technologies, we found that the neuroendocrine groups had more TP53 mutations and SCCC‐I had more PIK3CA mutations. Multiplex immunofluorescence validated these subtypes and SCCC‐I was an independent prognostic factor of overall survival. These results provide insights into SCCC tumor heterogeneity and potential therapies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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Section: Discussionmentioning

confidence: 99%

Multiomics sequencing and immune microenvironment characteristics define three subtypes of small cell neuroendocrine carcinoma of the cervix

Pan,

Yan,

Yuan

et al. 2024

The Journal of Pathology

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“…For example, in the lung and prostate, transdifferentiations from an AdC to neuroendocrine tumor occur in response to targeted therapy [ 14 , 15 ]. However, in cervical cancer, the development of a neuroendocrine carcinoma from a small human papillomavirus–associated cervical adenocarcinoma has been reported lately [ 16 ]. Defining the molecular mechanisms of neuroendocrine transformation in cervical cancer remains a question.…”

Section: Discussionmentioning

confidence: 99%

Impact of the initial site of metastases on post-recurrence survival for neuroendocrine cervical cancer

et al. 2022

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Objective To summarize the risk factors and emphasize the prognostic importance of the site of recurrent neuroendocrine cervical cancer (NECC). Methods We enrolled 88 patients who developed recurrence after radical surgery for pathological stage I–IVa primary NECC between January 2003 and 30 December 2020 and classified these cases into 7 groups based on the initial recurrence. The risk factors for post-recurrence survival (PRS) were analyzed by Kaplan–Meier and Cox regression methods. Results Among 88 NECC patients, nearly all patients (95.50%) experienced progression within 3 years. The time to progression was significantly longer in patients with lung recurrence than in patients without lung recurrence (p = 0.008). After the first recurrence, the median follow-up was 11.1 months (range 2.37–65.50 months), and the 5-year PRS was only 20.6%. The depth of invasion in the primary surgery, number of recurrent sites, abdominal organ recurrence were correlated with PRS by univariate analysis. Multivariate analyses revealed that the number of recurrent sites (p = 0.025) and abdominal organ recurrence (p = 0.031) were independent prognostic factors. Notably, the combination of immune checkpoint inhibitors and chemotherapy, with or without surgery, showed a 43.8% objective response rate in recurrent NECC. Conclusion Patients with abdominal organ recurrence need more sophisticated therapy. The combination of immune therapy and chemotherapy might be an opportunity for recurrent NECC.

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“…Ovarian preservation and ovariectomy have always been controversial for early cervical adenocarcinoma patients (9)(10)(11). The main issues are the risk of ovarian metastasis, the poor prognosis of such patients, and the need to preserve ovarian function in young women.…”

Section: Introductionmentioning

confidence: 99%

Influence of ovarian-sparing surgery and ovariectomy on prognosis in early cervical adenocarcinoma: a systematic review and meta-analysis

Sheng¹,

Yi²,

Nie³

2022

Gland Surg

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Background: The effect of ovarian-sparing surgery versus ovariectomy on prognosis in early cervical adenocarcinoma is controversial. The aim of this study was to compare the effect of ovary preservation versus ovariectomy on the prognosis of patients with cervical adenocarcinoma.Methods: A literature search was conducted of the PubMed, Excerpta Medica Database, Medline, Central, China National Knowledge Infrastructure databases, and China Science Periodical Database. The subjects of the literature study were patients with cervical adenocarcinoma. The literature compared the prognostic impact of ovary-sparing versus ovariectomy surgery. The Newcastle-Ottawa Scale was used to evaluate the quality of the articles. The Chi-square test was used to test the heterogeneity of the articles, and the randomeffects model was used if the results indicated heterogeneity. A subgroup analysis and sensitivity analysis were used to examine the source of heterogeneity. If there was no heterogeneity among the articles, a fixed-effects model was used. Publication bias was evaluated using funnel plots and Egger test.Results: A total of 3,467 patients with stage IA-IB cervical adenocarcinoma from 5 articles were included in the meta-analysis, of whom 995 had ovarian preservation and 1,895 had ovariectomy. There was no statistically significant difference in the 5-year overall survival (OS) between the stage IA-IIB cervical adenocarcinoma patients in the ovariectomy group and the ovarian preservation group (P=0.14). Additionally, there was no heterogeneity among these articles, and no publication bias (P>0.05). There was no significant difference in the 5-year progression free survival (PFS) between the stage IA-IIB cervical adenocarcinoma patients in the ovariectomy group and the ovarian preservation group (P=0.11). Additionally, there was no heterogeneity among these articles, and no publication bias (P>0.05). There was no significant difference in the 5-year disease specific survival (DSS) between the stage IA-IIB cervical adenocarcinoma patients in the ovariectomy group and the ovarian preservation group (P=0.48). Additionally, there was no heterogeneity among these articles, and no publication bias (P>0.05).Conclusions: There was no statistically significant difference in 5-year OS, PFS and DSS between ovarian-sparing surgery and oophorectomy for early-stage cervical adenocarcinoma. High-quality randomized controlled trials are still needed to verify this conclusion.

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Pelvic and Ovarian Recurrence of Small HPV-associated Cervical Adenocarcinoma With Transformation to Neuroendocrine Carcinoma

Cited by 3 publications

References 22 publications

Multiomics sequencing and immune microenvironment characteristics define three subtypes of small cell neuroendocrine carcinoma of the cervix

Multiomics sequencing and immune microenvironment characteristics define three subtypes of small cell neuroendocrine carcinoma of the cervix

Impact of the initial site of metastases on post-recurrence survival for neuroendocrine cervical cancer

Influence of ovarian-sparing surgery and ovariectomy on prognosis in early cervical adenocarcinoma: a systematic review and meta-analysis

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