The Methylation Test Is Highly Sensitive for HPV-Associated Endocervical Adenocarcinoma and Could Be Helpful as a Cytological Ancillary Test in Women With a PAP-Smear Diagnosis of Severe Glandular Lesion (AGC–NEO+)

Abstract

Objective

The limitations of PAP smears in diagnosing severe cervical glandular lesions motivate the development of ancillary methods to facilitate their detection. This prospective cytology–histology and molecular study aims to investigate methylation test performance by establishing the test sensitivity and its relevance to patient management.

Method

LBC samples were prospectively acquired after 3 months following the primary conventional PAP-smear screening diagnosis of AGC–NEO (atypical glandular cells, favour neoplastic) and AIS. An HPV test and methylation test were performed. Corresponding subsequent biopsy reports were collected.

Results

Seven hundred and seventy Pap tests were signed out as AGC–NEO+. Complete study data were available for 85 cases (AIS in 46 cases, EA in 39 cases) that were further analysed. The methylation test was positive in 95.3% (81/85) cases, negative in 3.5% (3/85, AIS in two cases, EA in one case) and unanalysable in one sample (1.2%). HPV genotyping revealed a multi-infection rate of 29%. The presence of HPV types 16 and 18 was detected in 84% (72/85) of lesions, and HPV type 45 in 12% (10/85).

Conclusions

The methylation test shows a high sensitivity of 95.3% and reliably identifies histologically confirmed AIS+ lesions. This argues for further investigation into its performance characteristics and consideration of its use, especially as a pre-surgical triaging test in sensitive cases if the AIS+ lesion is suspected in pregnant women or nullipara.