HPV‐negative carcinoma of the uterine cervix: a distinct type of cervical cancer with poor prognosis

Objective Using highly sensitive polymerase chain reaction (PCR) techniques, we reanalysed all cervical carcinomas (CCs) found to be human papillomavirus (HPV)‐negative by Hybrid Capture 2 (HC2) to determine the prevalence of true HPV‐negativity. We also evaluated the characteristics of the patients with tumours with confirmed HPV‐negativity. Design Observational study. Setting Barcelona, Spain. Population A cohort of 136 women with CC (32 adenocarcinomas, 104 squamous cell carcinomas) who had pre‐treatment HC2 testing. Methods All negative cases were reanalysed and genotyped for HPV using three PCR assays (SPF10, GP5+/6+ and E7‐specific assay). Main outcome measures Percentage of confirmed HPV‐negative and HPV‐positive tumours. Clinicopathological features and disease‐free survival (DFS) and overall survival (OS) of both groups. Results Fourteen of 136 women (10.2%) were negative for HPV by HC2. After reanalysis by PCR‐based techniques only 8/136 (5.8%) tumours were confirmed as HPV‐negative, whereas in six cases different HPVs were identified [HPV–11, −16 (two tumours), −18, −45, and −68]. Confirmed HPV‐negativity was more frequent in adenocarcinomas than in squamous cell carcinomas (5/32, 15.6% versus 3/104, 2.9%, respectively; P = 0.017). Patients with CCs with confirmed HPV‐negativity had significantly worse DFS than women with HPV‐positive tumours [51.9 months (95% CI 12.2–91.7 months) versus 109.9 months (95% CI 98.2–121.5 months); P = 0.010]. In the multivariate analysis HPV‐negativity and International Federation of Gynecology and Obstetrics (FIGO) staging were associated with increased risk of progression and mortality. Conclusions An HC2‐negative result is an uncommon finding in women with CC, but in almost half of these cases HPVs are identified by more sensitive techniques. CCs with confirmed HPV‐negativity are more frequently adenocarcinomas, and seem to be associated with worse DFS.