Mixed and nonvaccine high risk HPV types are associated with higher mortality in Black women with cervical cancer

Rachelle P Mendoza,Zaheer Bukhari,M A Haseeb,Tahmineh Haidary,Raj Wadgaonkar,Raag Agrawal,Courtney Connelly,Elmer Gabutan,Ying Yin Zhou,Wen-Ching Lee,Raavi Gupta,Yi-Chun Lee

doi:10.1038/s41598-021-93485-1

Rachelle P Mendoza, Zaheer Bukhari + Show 10 more

Open Access

https://doi.org/10.1038/s41598-021-93485-1

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Abstract

We studied the incidence of HPV genotypes in mostly Black women with cervical carcinoma and correlated histopathologic tumor characteristics, immune markers and clinical data with survival. Disease-free survival (DFS) and overall survival (OS) were recorded for 60 months post-diagnosis. Fifty four of the 60 (90%) patients were Black and 36 (60%) were < 55 years of age. Of the 40 patients with typeable HPV genotypes, 10 (25%) had 16/18 HPV genotypes, 30 (75%) had one of the non-16/18 HPV genotypes, and 20 (50%) had one of the 7 genotypes (35, 39, 51, 53, 56, 59 and 68) that are not included in the nonavalent vaccine. Mixed HPV infections (≥ 2 types) were found in 11/40 (27.5%) patients. Patients infected with non-16/18 genotypes, including the most common genotype, HPV 35, had significantly shorter DFS and OS. PD-L1 (p = 0.003), MMR expression (p = 0.01), clinical stage (p = 0.048), histologic grade (p = 0.015) and mixed HPV infection (p = 0.026) were independent predictors of DFS. A remarkably high proportion of cervical cancer cells in our patients expressed PD-L1 which opens the possibility of the use of immune checkpoint inhibitors to treat these cancers. Exclusion of the common HPV genotypes from the vaccine exacerbates mortality from cervical cancer in underserved Black patients.

Highlights

We studied the incidence of human papilloma virus (HPV) genotypes in mostly Black women with cervical carcinoma and correlated histopathologic tumor characteristics, immune markers and clinical data with survival
Sixty patients diagnosed with squamous cell carcinoma of the cervix were included in this study
All of the patients received standard treatment protocol as per the National Comprehensive Cancer Network (NCCN) guidelines based on clinical stage (FIGO classification)

Summary

Introduction

We studied the incidence of HPV genotypes in mostly Black women with cervical carcinoma and correlated histopathologic tumor characteristics, immune markers and clinical data with survival. Patients infected with non-16/18 genotypes, including the most common genotype, HPV 35, had significantly shorter DFS and OS. Exclusion of the common HPV genotypes from the vaccine exacerbates mortality from cervical cancer in underserved Black patients. Studies adjusted for cultural and socioeconomic factors have revealed a biological basis of higher mortality in cervical carcinoma in Black women[4]. Black patients have a preponderance of non-16/18 HPV infections, including some rare genotypes with less known pathogenesis and outcomes. Because of sparse data the efficacy of immune-checkpoint inhibitors has not been established as a first line therapy in primary cervical carcinoma, especially in Black patients, who commonly present with advanced stage disease

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