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.
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.
Authors: S Stolnicu; I Barsan; L Hoang; P Patel; C Terinte; A Pesci; S Aviel-Ronen; T Kiyokawa; I Alvarado-Cabrero; E Oliva; K J Park; N R Abu-Rustum; M C Pike; R A Soslow Journal: Gynecol Oncol Date: 2018-05-30 Impact factor: 5.482
Authors: Anjelica Hodgson; Kay J Park; Bojana Djordjevic; Brooke E Howitt; Marisa R Nucci; Esther Oliva; Simona Stolnicu; Bin Xu; Robert A Soslow; Carlos Parra-Herran Journal: Am J Surg Pathol Date: 2019-01 Impact factor: 6.394
Authors: Jonathan E Leeman; Yi Li; Andrew Bell; Suleman S Hussain; Rahul Majumdar; Xiaoqing Rong-Mullins; Pedro Blecua; Rama Damerla; Himanshi Narang; Pavithran T Ravindran; Nancy Y Lee; Nadeem Riaz; Simon N Powell; Daniel S Higginson Journal: Proc Natl Acad Sci U S A Date: 2019-10-07 Impact factor: 11.205