International Endocervical Adenocarcinoma Criteria and Classification (IECC): An Independent Cohort With Clinical and Molecular Findings

Abstract

and Classification (IECC) has reorganized the classification of endocervical adenocarcinomas (ECAs), separating them into human papilloma virus (HPV)-associated (HPVA) and HPVA independent (HPVI) categories. In this study, we sought to revalidate the IECC clinical findings in an independent cohort and assess the mutational differences between HPVA and HPVI ECAs using next generation sequencing. Consecutive cases of ECAs were reclassified under the IECC. Clinicopathologic information was collected and tissue was sent for targeted next-generation sequencing in 33 genes. Associations between HPV status, clinicopathologic parameters and mutation status, with survival were evaluated. The series comprised of 85/100 HPVA (63 HPVA-usual type, 4 villoglandular, 3 mucinous intestinal, 15 mucinous not otherwise specified) and 15/100 HPVI (9 gastric, 4 mesonephric, 1 clear cell, 1 not otherwise specified). HPVA ECAs presented at a lower age (P = 0.001), smaller tumor sizes (P = 0.011), less margin positivity (P = 0.027), less Silva pattern C (P = 0.002), and lower FIGO stages (P = 0.020). HPVA had superior survival compared with HPVI ECA [overall survival (P = 0.0026), disease-specific survival (P = 0.0092), and progression-free survival (P = 0.0041)]. Factors that correlated with worse prognosis irrespective of HPV status were FIGO stage, positive margins and lymphovascular invasion (Po0.05). TP53 mutations were detected in a significantly higher proportion of HPVIs than HPVAs (Poo0.001). The study revalidates the IECC system by reaffirming the clinical and prognostic differences between HPVA and HPVI ECAs in an independent dataset.

Independent validation of distinct clinicopathological features and prognosis among usual-type, mucinous-type and gastric-type endocervical adenocarcinoma categorised by new WHO classification (2020)

“…A recent investigation on a small cohort of EACs reconfirmed that HPVA had better survival than HPVI. 13 In addition, our study indicated that mutant-type p53 expression was substantially higher in HPVI than in HPVA, and was a significant indicator for poor survival in EAC. A prospective cohort study showed that p53 over expression was an adverse biomarker for patient survival in cervical carcinomas including EAC.…”

“…The IECC (the prototype of WHO classification, 2020) not only had superior diagnostic reproducibility among gynecological pathologists compared to the fourth WHO classification (2014), but also showed excellent prediction of HPV status. 4,12,13 More importantly, emerging evidence has demonstrated the relevance of the classification with the clinical outcomes. [13][14][15] In this retrospective study, we independently validated the clinicopathological and pathogenic significance of the novel WHO classification in a large cohort of EAC.…”

“…4,12,13 More importantly, emerging evidence has demonstrated the relevance of the classification with the clinical outcomes. [13][14][15] In this retrospective study, we independently validated the clinicopathological and pathogenic significance of the novel WHO classification in a large cohort of EAC.…”

“…Similar results have been reported previously. [12][13][14] The IECC cohort showed that HPVA were less frequently associated with LVSI, lymph node metastasis and distant recurrence, and had superior clinical outcomes, compared to HPVI. 14 Likewise, Hodgson et al, 12 reported that tumour recurrence and tumour-related mortality occurred more frequently in HPVI than in HPVA.…”

Case Report: Giant Pelvic Cystic Appearance—An Unusual Feature of Uterine Cervical Adenocarcinoma

“…After diagnosis in two large pathological centers, the patient was considered to have HPVA, and the positive immunohistochemical P16 and HPV E6 and E7 mRNA were also consistent with this diagnosis. The prognosis of HPVA is better than that of non-HPV cervical adenocarcinoma ( 8 ). There is no standard FIGO staging method for cervical adenocarcinoma of large cysts.…”