Introduction Human papillomavirus (HPV)-independent cervical cancer account for approximately 5% of cervical cancer, especially in adenocarcinomas. These subtypes have poorer prognosis and require clinical attention. Recent guidelines on cervical cancer screening recommend primary HPV screening rather than conventional cytology test. This study evaluated the accuracy of cytology test in HPV-independent (HPVI) cervical adenocarcinoma and compared it to HPV-associated (HPVA) cervical adenocarcinoma.

Methods Medical records of 94 patients with HPVI cervical adenocarcinoma were collected after pathologic review. Patients with HPVA cervical adenocarcinoma from January 2019 to November 2021 were set as a control group. Patients who had not performed cytology test before diagnosis were excluded. Pathologic report of cervical biopsy and the results of most recent cytology test prior to diagnosis were investigated. Histologic subtype of cervical cancer was divided according to 2020 WHO Female Genital Tumors classification.

Results Eighty-one patients in HPVI group and 110 patients in HPVA group were included in final analysis. Among HPV-associated adenocarcinoma, usual-type was the most common type (80.9%, 89/110). In HPV-independent adenocarcinoma, there were 59 (72.8%) cases of gastric-type, 10 (12.3%) cases of clear cell-type, 5(6.2%) cases of endometrioid-type, and 3(3.7%) cases of mesonephric-type adenocarcinoma. Patients with HPV-associated cancer had abnormal cytology test result in 79.1% (87/110), with false-negative rate of 20.9% (23/110). In patients with HPV-independent adenocarcinoma, 63.0% (51/81) had abnormal cytology test result, with false-negative rate of 37.0% (30/81).

Conclusion/Implications The false-negative rate of cytology test was higher in HPV-independent adenocarcinoma than in HPV-associated adenocarcinoma. Cervical cytology test is not accurate for screening HPV-independent adenocarcinoma.