Endocervical adenocarcinoma is divided into human papillomavirus (HPV)–associated (HPVA) and HPV-independent (HPVI) in the 5h edition of the World Health Organization (WHO) tumor classification launched in 2020. However, the validity of the morphological criteria used for biopsy specimens in real-world practice remains undetermined.


To validate the utility of the 5th edition of the WHO classification for biopsy samples, focusing on its diagnostic criteria with the aid of ancillary studies.


We retrieved 217 cases of endocervical adenocarcinoma from 6 institutions, in which glass slides of both biopsy and resection specimens were available for review. Concordance between the biopsy and resection specimen diagnoses was evaluated. For discordant diagnoses, an algorithmic approach with ancillary studies proposed by the international group was applied to confirm their utility to improve the accuracy of biopsy diagnosis.


The biopsy diagnosis matched the resection specimen diagnosis in 197 cases (concordance rate, 91%; κ = 0.75). The concordance rate was significantly higher for HPVA than HPVI (95% versus 81%, P = .001). There were no significant differences in the proportions of HPVA and HPVI or the accuracy of biopsy diagnosis between the participating institutions. All 19 discordant cases with unstained glass slides available were accurately recategorized as HPVA or HPVI using HPV in situ hybridization; p16 immunohistochemistry was positive in 3 of 9 cases of gastric-type HPVI that were negative by in situ hybridization.


The 5th edition of the WHO criteria for biopsy diagnosis of endocervical adenocarcinoma distinguishes HPVA from HPVI well when ancillary studies are adequately applied.

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Competing Interests

The authors have no relevant financial interest in the products or companies described in this article.

Author notes

The preliminary findings of this project were presented as a poster at United States and Canadian Academy of Pathology 112th annual meeting in New Orleans, Louisiana; March 13, 2023.