Cervical HPV-independent adenosquamous carcinoma: report of a case series

Adenosquamous carcinoma is an uncommon cervical malignancy which is composed of a morphologically recognisable malignant squamous and glandular component. In the current 5th edition WHO Classification of Female Genital Tumours, adenosquamous carcinoma of the cervix is regarded as a high-risk human papillomavirus (HPV)-associated neoplasm. However, in recent years, there have been occasional reports of cervical HPV-independent adenosquamous carcinomas. We report a series of 5 cervical HPV-independent adenosquamous carcinomas in women aged 45 to 68 years; 4 of 5 patients were postmenopausal. The percentage of the squamous component ranged from 10 to 90%. In all cases, the glandular component was gastric-type. All tumours exhibited negative/non-block-type staining with p16 and were also negative for HPV on molecular testing. Molecular testing (4 of 5 cases) revealed no recurrent variants. However, in individual cases, pathogenic or likely pathogenic variants were present in BRAF, CDK12, RB1, FGFR2, FGFR3, BRCA1, KRAS, CDKN1A, CDKN2A, TP53, and STK11. In addition, deletions of CDKN2A/CDKN2B and TP53 were present in 1 case. The tumours were advanced stage at diagnosis: stage IIB (1 case), IIIC1 (2 cases), and IVB (2 cases). Our findings suggest that cervical adenosquamous carcinoma should be classified into HPV-associated and HPV-independent types and this should be reflected in updated WHO Classifications.