HPV-negative tumors of the uterine cervix

Abstract

Human papillomaviruses (HPV) are the causative agents of virtually all cervical carcinomas. Nevertheless, a small proportion of cervical cancer are negative for HPV, although the significance of this finding remains unclear. We aimed to provide insight into the differential clinico-pathological characteristics of this unusual subset of HPV-negative cervical cancer. We performed HPV-DNA detection using a highly sensitive PCR test (SPF10) and p16 immunostaining in 214 cervical carcinomas specimens from women treated at the Gynecological Oncology Unit of the Hospital Clinic (Barcelona, Spain) from 2012 to 2015. The clinical and pathological characteristics,

Human Papillomavirus-Negative Cervical Cancer: A Comprehensive Review

“…A meta-analysis of 2838 cervical cancer cases from 17 studies revealed that HPV positivity correlated with better prognosis (OS: HR=0.610, p =0.001; disease-free survival: HR=0.362, p <0.001) ( 68 ). To date, three other studies have reached the same conclusion that HPV-negative cervical cancer is associated with poor prognosis ( Table 3 ) ( 57 – 59 ). Nevertheless, a 10-year follow-up study of 204 patients with cervical cancer revealed that the 5-year OS rate of HPV-negative and HPV-positive patients was 82% and 58% ( p =0.003), respectively, indicating that HPV infection was significantly correlated with poor OS of patients ( 69 ).…”

“…HPV-negative patients are prone to develop advanced FIGO stage and lymphatic space invasion prior to diagnosis, resulting in poor prognosis ( Table 3 ) ( 57 , 58 ). A multicenter study revealed that 62.5% of HPV-negative adenocarcinomas were stage II or higher, while 83.7% of usual type cases were stage I at diagnosis, which concurred with previous studies ( 60 ).…”

The new (Version 9) American Joint Committee on Cancer tumor, node, metastasis staging for cervical cancer

“…The need for this specific update, which does not affect the TNM categories, is that HPV-associated cervical cancer has a more favorable prognosis than HPVindependent cervical cancer. [6][7][8] Approximately 10% of cervical carcinomas are HPV-negative. 6,7 In one study, patients who had HPV-negative tumors were older, had more advanced disease at diagnosis, and were more frequently diagnosed with nonsquamous histology; moreover, they had a significantly worse disease-free survival (60 months vs 132 months) and overall survival (77 months vs 154 months) compared with women who had HPV-positive tumors.…”

Targeting the PD-1 Axis with Pembrolizumab for Recurrent or Metastatic Cancer of the Uterine Cervix: A Brief Update

“…A small proportion of CCs (<5%) are truly HPV-negative after sensitive HPV assessment. These tumors are more frequently of the non-squamous subtype, diagnosed at advanced stages, show higher prevalence of lymph node metastases, and have an impaired prognosis [7,8]. HPV-negative CCs have distinct molecular characteristics that show similarities with endometrial cancer, while having a significantly higher epithelialmesenchymal transition mRNA score and a lower frequency of the APOBEC mutagenesis signature compared to their HPV-positive counterparts [9,10].…”