High-risk HPV E6/E7 mRNA in situ hybridization in endocervical glandular neoplasia: performance compared with p16INK4a and Ki67 immunochemistry

Tingting Chen; Jing Li; Shunni Wang; Yan Ning; Xianrong Zhou; Yiqin Wang

High-risk HPV E6/E7 mRNA in situ hybridization in endocervical glandular neoplasia: performance compared with p16^INK4a and Ki67 immunochemistry

Am J Transl Res. 2019 Oct 15;11(10):6498-6506. eCollection 2019.

Authors

Tingting Chen¹, Jing Li¹, Shunni Wang¹, Yan Ning¹, Xianrong Zhou¹, Yiqin Wang¹

Affiliation

¹ Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University No. 128, Shenyang Road, Shanghai 200082, China.

PMID: 31737201
PMCID: PMC6834507

Abstract

Objective: HR-HPV E6/E7 mRNA in situ hybridization (HR-HPV RISH) can detect HPV-driven endocervical glandular neoplasia. Our aim was to compare its diagnostic performance with the conventional p16^INK4a and Ki67 immunochemistry (IHC).

Methods: HR-HPV RISH and IHC were performed in normal cervix (n = 70), reactive cervix (n = 60), adenocarcinoma in situ (AIS) (n = 92), endocervical adenocarcinoma (ECA) and adenosquamous carcinoma (n = 21) samples (n = 163). The sensitivities and specificities of the three markers were compared in the benign, AIS, HPV-associated adenocarcinoma (HPVA) and non HPV-associated adenocarcinoma (NHPVA) samples, and in 39 endocervical curettage specimens containing endometrial and HPV-associated neoplastic glands. Finally, the inter-observer agreement rate for the three markers were calculated.

Results: The sensitivities of HR-HPV RISH, P16^INK4a and Ki67 were 100% for the HPV-related glandular neoplasia and HPVAs in ECAs, while the specificity of HR-HPV RISH (100%) were higher than the other two (88.89% and 17.77% for P16^INK4a and Ki67 respectively) in the HPVAs. Furthermore, HR-HPV RISH was more specific than either p16^INK4a block+ or Ki67 in the endocervical curettage specimens and in HPVAs with poor differentiation. Finally, the inter-observer agreement for HR-HPV RISH was higher than that for the morphological, p16^INK4a block+ and Ki67 markers (99.67% vs. 95.10%, 99.35% and 90.85% respectively).

Conclusions: HR-HPV RISH is highly sensitive and specific for HPV-driven endocervical glandular neoplasia compared to p16^INK4a and Ki67, and should be incorporated for ECA diagnosis.

Keywords: Cervical glandular neoplasia; HR-HPV; Ki67; P16INK4a; mRNA RISH.