The complex relationship between human papillomavirus and cervical adenocarcinoma

Human Papillomavirus (HPV) is reported in 60-100% of cervical adenocarcinoma (CADC) globally. We investigated this relationship in a hospital-based survey in China. 718 CADC samples from nine Chinese regions were analysed. Expert pathologists reviewed cases with p16 and progesterone receptor immunostaining. Cases were tested for HPV using whole-tissue sections (WTS) and laser-capture microdissection. All cases were HPV-tested by L1 based broad-spectrum SPF10 -DEIA-LiPA25 PCR. Negative cases were tested for DNA adequacy and with E6 oncogene, type-specific HPV PCRs. Using WTS-PCR CADC showed overall 75% HPV-positivity (33-100% for different histological types). LCM-PCR showed that none of minimal deviation or serous CADC, and <10% of all clear cell and endometrioid CADC were HPV-positive in tumour cells. Usual and adenosquamous CADC showed a single HPV genotype in 60 and 78% cases. In some cases, HPV was found in adjacent cervix but not in tumour. HPV 16, 18 and 45 accounted for 90% of HPV in tumour cells. Patients with HPV-positive tumours were on average 6 years younger and presented at a lower clinicopathological stage as compared to patients with HPV-negative cancers. CADC is diverse pathologically and in HPV status. Special histopathological tumor subtypes may develop through different cellular and molecular pathways. Between 20 and 40% usual and adenosquamous types, in particular these diagnosed in older women and at advanced FIGO stages, are not driven by oncogenic HPV. In these cases HPV may not be involved in carcinogenisis or maybe lost during tumour progression.