Small proportion of cervical cancers (CC) are negative for human papillomavirus (HPV), even using highly sensitive HPV tests. It has been suggested that HPV-negative CC may represent a biologically distinct subset of tumours carrying a poorer prognosis. However, the significance of HPV-negativity in CC remains unclear. We aimed to provide insight into the differential clinical, pathological, and prognostic characteristics of the unusual HPV-negative CCs.
A cohort of 215 women with CC diagnosed in the Hospital Clinic (Barcelona) from 1999 to 2014 underwent HPV testing using: 1)a highly sensitive polymerase chain reaction (PCR): SPF10PCR/DEIA/LiPA25 system for HPV-DNA detection and genotyping and 2)p16INK4a immunostaining. Clinical, histological and immunological characteristics of the women included were recorded.
Twenty one out of 215 tumors (9.8%) were negative for HPV-DNA detection. Nine of them (9/21;42.9%) showed also a negative p16INK4a immunostaining result. These double negative tumors were considered as confirmed HPV-negative CC. Within the confirmed HPV-negative CC, 5 were squamouscarcinoma, 2 were adenocarcinoma and 2 were neuroendocrine. Women with confirmed HPV-negative CC were diagnosed at advanced FIGO stage and showed worse disease free survival [47.5 months (95%CI:8.7-86.22 months) vs. 129.6 months (95%CI:116.22-143.01 months); p=0.009] and overall survival [72.1 months (95%CI:25.44-118.80 months) vs. 151.4 months (95%CI:139.70-163.05 months); p=0.056] than women with HPV-positive tumours.
DNA-HPV negative result is an uncommon finding in women with CC, and almost half of these cases show a positive p16INK4a immunostaining. Confirmed HPV-negative CC seems to be associated with advance FIGO stages and worse prognosis.