HPV Type Distribution in HIV Positive and Negative Women With or Without Cervical Dysplasia or Cancer in East Africa.

Ruby Doryn Mcharo ,Tessa Lennemann,Matilda Paul,Mercè Garí,Arne Kroidl,Jonathan Mnkai,Anifrid Mahenge,Bareke Msomba,Nhamo Chiwerengo,Laura Glasmeyer,Nicolas Schroeder,Mona Judick,Wolfram Mwalongo,Wilbert Mbuya,Mkunde Chachage,Otto Geisenberger,Elmar Saathoff,Asli Bauer,Magreth Sembo,Christof Geldmacher,Leonard Maboko,L López Torres ,Ralph J Lellé ,J France ,Michael Höelscher

doi:10.3389/fonc.2021.763717

Abstract

BackgroundWomen living with HIV in sub-Saharan Africa are at increased risk to develop cervical cancer (CC), which is caused by persistent infection with 13 oncogenic human papilloma viruses (HR-HPVs). It is important to accurately identify and target HIV-positive women at highest risk to develop CC for early therapeutic intervention.MethodsA total of 2,134 HIV+ and HIV− women from South-West Tanzania were prospectively screened for cervical cancer and precancerous lesions. Women with cervical cancer (n=236), high- and low-grade squamous intraepithelial lesions (HSIL: n=68, LSIL: n=74), and without lesion (n=426) underwent high-resolution HPV genotyping.ResultsEighty percent of women who were diagnosed with HSIL or LSIL were living with HIV. Any lesion, young age, HIV status, and depleted CD4 T cell counts were independent risk factors for HPV infections, which were predominantly caused by HR-HPV types. While multiple HR-HPV type infections were predominant in HIV+ women with HSIL, single-type infections predominated in HIV+ CC cases (p=0.0006). HPV16, 18, and 45 accounted for 85% (68/80) and 75% (82/110) of HIV+ and HIV− CC cases, respectively. Of note, HPV35, the most frequent HPV type in HSIL-positive women living with HIV, was rarely detected as a single-type infection in HSIL and cancer cases.ConclusionHPV16, 18, and 45 should receive special attention for molecular diagnostic algorithms during CC prevention programs for HIV+ women from sub-Saharan Africa. HPV35 may have a high potential to induce HSIL in women living with HIV, but less potential to cause cervical cancer in single-type infections.

Highlights

Cervical cancer (CC) is the fourth most frequent cancer in women globally with 570,000 new cases and 311,000 deaths in 2018
The decreasing prevalence of HPV16+ high-grade squamous intraepithelial lesions (HSIL) with age and high prevalence of HPV16+ cancers in women living with HIV, often at relatively young age, is consistent with the higher carcinogenic potential of HPV16, whereas HSILs associated with HPV35 may persist but not progress frequently, consistent with the high number of HV35+ HSILs in women living with HIV between 30 and 50 years of age
We originally hypothesized that higher proportions of none-16/ 18 high risk” (HR)-HPV types, which are frequently associated with squamous intraepithelial lesions in women living with HIV, cause CC more frequently in HIV+ than in HIV− women

Summary

Introduction

Cervical cancer (CC) is the fourth most frequent cancer in women globally with 570,000 new cases and 311,000 deaths in 2018. Sub-Saharan Africa (SSA) is the most heavily affected region globally; women here have the highest cumulative lifetime risk to develop CC—above 5% for many countries—and CC is the leading cause of death from malignancy in many SSA countries [2]. These “quasi epidemic” dimensions at least partially result from regional particularities, including a poor screening capacity for identification of women at risk for CC development and high prevalence of HIV infection. Women living with HIV in sub-Saharan Africa are at increased risk to develop cervical cancer (CC), which is caused by persistent infection with 13 oncogenic human papilloma viruses (HR-HPVs). It is important to accurately identify and target HIVpositive women at highest risk to develop CC for early therapeutic intervention

Methods

Results

Conclusion