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 ( CC s) found to be human papillomavirus ( HPV )‐negative by Hybrid Capture 2 ( HC 2) 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 HC 2 testing. Methods All negative cases were reanalysed and genotyped for HPV using three PCR assays ( SPF 10, GP 5+/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 HC 2. After reanalysis by PCR ‐based techniques only 8/136 (5.8%) tumours were confirmed as HPV ‐negative, whereas in six cases different HPV s 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 CC s 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 HC 2‐negative result is an uncommon finding in women with CC , but in almost half of these cases HPV s are identified by more sensitive techniques. CC s with confirmed HPV ‐negativity are more frequently adenocarcinomas, and seem to be associated with worse DFS .