HPV Infection Determines Prognosis in Patients with Invasive Cervical Cancer

High risk human papillomavirus infection reveals (hrHPV) to be a strong determinant of cervical cancer prognosis over 15 years after diagnosis. Investigators observed a 43% reduction in excess mortality in patients with hrHPV-positive invasive cervical cancer (ICC) compared with HPV-sequence–negative or polymerase chain reaction-hrHPV–negative ICC (excess hazard ratio [EHR] 0.57; 95% CI, 0.48-0.69).¹

The 5-year cumulative relative survival ratio (RSR) was 0.74 (95% CI, 0.72-0.75) in the hrHPV-positive group (n = 2524, 88.7%) and 0.45 (95% CI, 0.39-0.51) in the hrHPV-negative group (n = 321, 11.3%). No association between HPV risk group, clade, or number of HPV infections and prognosis was found.

The study followed all 2845 women from their date of diagnosis until December 31, 2016, emigration, or death. All 392 of 2845 invasive cervical cancer cases that were polymerase chain reaction–negative for HPV were subjected to RNA sequencing on the NovaSeq 6000 platform (Illumina), which identified an additional 169 cases as HPV-positive. The main outcome was all-cause mortality by the cutoff date. Investigators calculated the 5-year cumulative relative survival ratios compared with the female general population and used Poisson regression to estimate excess hazard ratios of all-cause mortality by infection with any of the 13 most oncogenic HPV types in the tumor. All models were adjusted for age, time since diagnosis, stage, histology, and education level.

There were 1165 deaths in the study. There were 1006 deaths (81.3%) occurred in the hrHPV-positive group and 159 deaths (18.7%) occurred in the HPV-negative group. The 5-year cumulative RSR was 0.74 (95% CI, 0.72-0.75) in the hrHPV-positive group vs 0.45 (95% CI, 0.39-0.51) in the hrHPV-negative group. When adjusting for age, time since cancer diagnosis, clinical characteristics, and education, these results translated to an estimated EHR of death of 0.57 (95% CI, 0.48-0.69).

HPV18-positive cases were associated with a 55%-increased excess mortality compared with HPV16-positive cases (EHR, 1.55; 95% CI, 1.23-1.94). Investigators found similar results when estimating the 5-year cervical cancer–specific mortality.

Reduced excess mortality in hrHPV-positive cases compared with hrHPV-negative didn’t change among patients who underwent surgery only (EHR, 0.29; 95% CI, 0.13-0.66). In the patients who first received surgery followed by radiochemotherapy, the finding was similar (EHR, 0.29; 95% CI, 0.13-0.66). In total, the EHR was 0.27, 95% CI (0.15-0.48).

Tumor histology included squamous cell carcinoma (n = 2109), adenocarcinoma (n = 526), adenosquamous cell carcinoma (n = 119), and other types (n = 91). At diagnosis, of patients with hrHPV-positive ICC 167 were aged less than 29 years (6.6%), 893 patients were aged 30 to 44 years (35.4%), 633 patients were aged 45 to 59 years (25.1%), 447 patients aged 60 to 74 years (17.7%), and 384 patients were older than 74 (15.2%). Of patients with ICC who were hrHPV-negative, there were 0 patients less than 29, 40 patients aged 30 to 44 years (12.5%), 69 patients aged 45 to 59 years (21.5%), 93 patients aged 60 to 74 years (29%), and 119 were older than 74 (37.1%).

Investigators determined that tumor hrHPV status is a novel biomarker with strong prognostic value for patients with ICC. To improve prognostic information for clinicians and women, investigators suggest HPV testing of cervical tumors should be considered in the routine clinical workup of cervical cancer.

_REFERENCE

_{Lei J, Arroyo-Mühr LS, Lagheden C, et al. Human papillomavirus infection determines prognosis in cervical cancer. Published online January 25, 2022. J Clin Oncol. 2022;JCO2101930. doi:10.1200/JCO.21.01930}