Abstract

Women living with HIV-1 are at high risk of infection with human papillomavirus of high carcinogenic risk (HR HPVs). M. tuberculosis (TB) promotes HPV infection and increases the risk to develop HPV-associated cancer. Our knowledge of persisting HR HPVs genotypes, and of the factors promoting HR HPV infection in people living with HIV-1 with clinical TB manifestations is sparse. Here, we analyzed 58 women living with HIV-1 with clinical TB manifestations (WLWH with TB) followed up in specialized centers in Russia, a middle income country endemic for HIV-1 and TB, for the presence in cervical smears of DNA of twelve HR HPV genotypes. DNA encoding HPV16 E5, E6/E7 was sequenced. Sociodemographic data of patients was collected by questionnaire. All women were at C2-C3 stages of HIV-infection (by CDC). The majority were over 30 years old, had secondary education, were unemployed, had sexual partners, experienced 2–3 pregnancies and at least one abortion, and were smokers. The most prevalent was HPV16 detected in the cervical smears of 38% of study participants. Altogether 34.5% of study participants were positive for HR HPV types other than HPV16; however, but none of these types was seen in more than 7% of tested samples. Altogether, 20.7% of study participants were positive for several HR HPV types. Infections with HPVs other than HPV16 were common among WLWH with generalized TB receiving combined ART/TB-therapy, and associated with their ability to work, indirectly reflecting both their health and lifestyle. The overall prevalence of HR HPVs was associated with sexual activity of women reflected by the number of pregnancies, and of HPV 16, with young age; none was associated to CD4+-counts, route of HIV-infection, duration of life with HIV, forms of TB-infection, or duration of ART, characterizing the immune status. Thus, WLWH with TB—especially young—were predisposed to infection with HPV16, advancing it as a basis for a therapeutic HPV vaccine. Phylogenetic analysis of HPV16 E5, E6/E7 DNA revealed no common ancestry; sequences were similar to those of the European and American HPV16 strains, indicating that HPV vaccine for WLWH could be the same as HPV16 vaccines developed for the general population. Sociodemographic and health correlates of HR HPV prevalence in WLWH deserve further analysis to develop criteria/recommendations for prophylactic catch-up and therapeutic HPV vaccination of this highly susceptible and vulnerable population group.

Highlights

  • Up to 4.5% of new cases of cancer registered worldwide—including cervical, anogenital, and head and neck cancers—are associated with human papillomavirus (HPV) infection [1]

  • Knowledge on the characteristics of high oncogenic risk HPV (HR HPV) variants persisting in women living with HIV-1 with tuberculosis, and demographic, clinical, social, and behavioral factors associated with acquisition of HR HPVs in the middle income countries is totally missing

  • Clinical forms of TB were classified according to TB classification accepted in Russia distinguishing more than 10 different forms of TB based on the clinical and morphological criteria, including generalized, infiltrative, fibrous-cavernous, disseminated TB tuberculous pleurisy, cirrhotic

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Summary

Introduction

Up to 4.5% of new cases of cancer registered worldwide—including cervical, anogenital, and head and neck cancers—are associated with human papillomavirus (HPV) infection [1]. Cervical cancer (CC) accounts for 83% of these cases. Health Organization (WHO), cervical cancer caused by high oncogenic risk HPV (HR HPV). Is the fourth most common cancer in women in the world [2]. In 2018, 311,000 women died from cervical cancer. WHO predicts that by 2045 cervical cancer will cause 491,000 deaths/year of women worldwide, and this figure will only increase in the future [3]. Today the average incidence of cervical cancer worldwide is 13.1 cases per

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