Epidemiology of Humanpapilloma Virus in East Africa

Abstract

ABSTRACT Background: Human papillomavirus (HPV) infection is a well-known etiological factor in cervical, anogenital, and head and neck malignancies. East Africa has the highest global prevalence of HPV infections and the highest cervical cancer mortality rate. However, the prevalence of HPV infections in mucous membranes other than the uterine cervix in this region remains limited. Additionally, the prevalence of co-infections across different mucosal sites is unknown. It is also unclear whether vaginal HPV screening could use be to identify women at risk of developing cervical cancer in East Africa. Furthermore, potential genetic variants associated with the susceptibility to HPV infection and the progression to cervical cancer in this population have yet to be identified. Aims: 1. To assess the prevalence and co-infection patterns of HPV in different mucous membranes among HIV-concordant couples living in Rwanda (Cohort B; Paper I). 2. To evaluate the prevalence of oral HPV infections in Zambia's general urban and rural populations (Paper II). 3. To determine the prevalence of HPV infections in the vaginal and cervical mucosa of women living with HIV (WLWH; Cohort A) in Rwanda (Paper III). 4. To investigate the prevalence of chronic HPV infections among women from Cohorts A and B and to examine whether single nucleotide polymorphisms (SNPs) are associated with the risk of HPV acquisition and the development of chronic HPV infections (Paper IV). Methods: Swab samples were collected from the oral cavity, oropharynx, vagina (both self-collected and physician-collected), uterine cervix, penis, and anus, along with Pap smears from the uterine cervix, from 50 HIV-positive concordant couples (cohort B) in Rwanda (Paper I). Vaginal and cervical swabs for HPV detection were collected from WLWH in cohort A (Paper III). WLWH from cohorts A and B were reassessed two years later (Paper IV), with follow-up swab samples for HPV and biomarker analysis, alongside blood tests. Male and female participants residing in Ndola (urban area) and Mansa (rural area) underwent oral swabs and oral clinical examinations (Paper II). Real-time polymerase chain reaction (RT-PCR) was conducted to detect 12 high-risk HPV types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) and two low-risk types (HPV6 and 11) across all studies (Papers I–IV). Pap smears were cytologically examined in Papers I and III. Single nucleotide polymorphisms (SNPs) were also analyzed in baseline blood samples using the Illumina Global Screening Array–Multi Disease version 3 (Paper IV). Participants were also interviewed regarding demographics and risk factors associated with HPV acquisition (Papers I–IV). Results: In Rwandan men and women living with HIV, high-risk HPV (HR-HPV) was detected in the oral cavity in 10% and 12% of cases, respectively, and in the oropharynx in 10% of men but not in women (Paper I). In contrast, HPV prevalence in Zambia’s urban and rural populations was low (<1%; Paper II). Among Rwandan women, HPV58, HPV52, HPV51, and HPV16 were the most common vaginal and cervical types, with one-third of WLWH co-infected with multiple types (Paper III). HR-HPVs were found in the cervix of 24% (Cohort B) and 38% (Cohort A) of women and vaginal samples collected by physicians in 30% and 39% of women, respectively. HR-HPV status showed high concordance between self-collected and physician-collected vaginal samples (κ = 0.70) and between vaginal and cervical samples (κ = 0.54–0.83). Anal HR-HPV infections were higher in women than men (24% vs. 2%, p = 0.002), while only 22% of HR-HPV infections were shared between partners (Paper I). Lastly, rs13158830 in PPARGC1B was the most significant SNP linked to chronic HR-HPV infection (Paper IV). Conclusions: HPV infections are prevalent among women and men living with HIV in Rwanda. Self-collected HPV screening has proven to be both feasible and representative of cervical HPV status, offering a promising approach to increasing cervical cancer screening rates among women in Rwanda. Additionally, we have identified unique SNPs associated with an elevated risk of developing chronic HPV infections. These genetic markers may potentially be used in the future to identify individuals at higher risk of cervical cancer, enabling more targeted prevention strategies.

Keywords: HPV, screening, biomarker, single nucleotide polymorphism, Rwanda, Zambia