Histological classification of uterine cervical adenocarcinomas: Its alteration and current status

Adenocarcinomas (ADCs) of the uterine cervix are relatively minor compared to squamous cell carcinomas. However, ADCs are histologically and histogenetically unique, especially because they can be with or without human papillomavirus (HPV) infection. At present, ADCs are divided into tumors as HPV-associated ADCs (HA-ADCs) and HPV-independent ADCs (HI-ADCs), including adenocarcinomas in situ (AIS) as their precursor, both of which consist of variable histological types. The usual-type accounts for the majority of HA-ADCs, and the gastric-type is a representative of HI-ADCs. Notably, it is clinicopathologically significant to differentiate between HA-ADCs and HI-ADCs because of the discrepancy in prognosis between them. Although relatively rare in comparison with HPV-associated AIS (HA-AIS), HPV-independent AIS (HI-AIS) has gradually attracted attention since gastric-type ADC (g-ADC) was introduced in the World Health Organization Classification 4th ed. (2014). Occasional HA-ADCs and HI-ADCs, including HA-AIS and HI-AIS, require p16 immunostaining, in situ hybridization, or HPV testing to differentiate between them because morphological features alone cannot often be conclusive for the diagnosis. A system focusing on the infiltrative pattern has been introduced due to its clinicopathological value. Staging criteria of HA-ADCs with polypoid/exophytic growth, recommended by the International Collaboration on Cancer Reporting, may supplement the International Federation of Gynecology and Obstetrics staging system for clinical management and treatment.