Cytology, High-Risk Human Papillomavirus Testing and Serum CA19-9 in a Large Cohort of Patients with Invasive Cervical Adenocarcinomas: Correlation with a New Pathogenetic Classification

AIMS: This study aims to investigate the screening value of cytology, high-risk human papillomavirus (hrHPV) testing and serum CA19-9 in cervical adenocarcinomas. MATERIALS AND METHODS: We employed HPV RNA in situ hybridization and immunohistochemistry to reclassify 209 cervical adenocarcinomas according to the International Endocervical Adenocarcinoma Criteria and Classification (IECC). We analyzed the diagnostic value of cytology, hrHPV testing and serum CA19-9 in these tumors and their detection variance among IECC histotypes. RESULTS: We found that the sensitivity of cytology or hrHPV test alone was 74.1% (129/174) or 72% (131/182), respectively. Non-HPV related adenocarcinoma showed a lower detection rate of cytology (60%, 27/45 vs. 79.1%, 102/129, p=0.017) or hrHPV testing (9.8%, 4/41 vs. 90.1%, 127/141, p<0.0001), compared to HPV-related adenocarcinomas. The cytology and hrHPV co-testing significantly demonstrated a higher sensitivity (151/165, 91.5%) than single test alone (p<0.001). Nevertheless, the sensitivity of co-testing was substantially lower for gastric-type adenocarcinoma (GAC) (74.1%, 20/27) than that for non-GAC (94.9%, 131/138) (p=0.001). Serum CA19-9 (>40 U/mL) identified 44.1% (15/34) GACs including 75% (6/8) that were missed by co-testing, much higher than for non-GACs (10.7%, 19/177; p<0.001). The combination of cytology, hrHPV test and serum CA19-9 enhanced the detection rate of GACs (92.9%, 26/28). CONCLUSION: We conclude that cytology and hrHPV co-testing is not very effective for non-HPV related adenocarcinoma, particularly for GAC. As such, additional serum CA19-9 should be given in women with potential cancer risks.