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

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.

Cervical human papillomavirus genotypes in a high HIV setting: A scoping review of a decade of human papillomavirus epidemiological research in Botswana

“…In general, HPV-16 remains by far the most common high-risk HPV genotype in Botswana among women with pre-cancer and cancer, in both HIV-positive and HIV-negative. The data showed are consistent with the previously published literature investigating women living with HIV ( 37 ), but cannot fully sustain the hypothesis that HIV may substantially alters the relative carcinogenic activity of less virulent high-risk HPV genotypes as reported previously worldwide, in East Africa and in Zimbabwe ( 37 – 40 ). According to the available literature on Botswana, HPV-16 and HPV-18, that are known to be more prevalent in cervical cancer cases, seem to be lower in young women and increase with age and severity of the cervical lesions.…”

High-risk human papillomavirus genotype distribution among women living with and at risk for HIV in Africa

“…We and others have previously studied HPV-35 infections in WLWH with precancerous or cervical cancer [17,30,34]. Of note, in our recently published study, HPV-35 infections occurred frequently in women with precancerous lesions (27% of WLWH with such lesions), typically in the presence of other high-risk HPV genotypes with a similar pattern, yet at a lower frequency (11%) observed in cervical cancer cases [23]. In contrast, HPV-16/18 and also HPV-45 were often detected as single infections in cancers in the same study [23].…”

“…Of note, in our recently published study, HPV-35 infections occurred frequently in women with precancerous lesions (27% of WLWH with such lesions), typically in the presence of other high-risk HPV genotypes with a similar pattern, yet at a lower frequency (11%) observed in cervical cancer cases [23]. In contrast, HPV-16/18 and also HPV-45 were often detected as single infections in cancers in the same study [23]. Hence, the RR of HPV-35 infections to cause cervical cancer progression in WLWH should be studied more in detail.…”

“…In a recent study in East Africa, HPV-35 was the second most frequent HPV type in precancerous lesions and was still detected in 11% of cervical cancer cases in WLWH. However, HPV-35 typically occurred together with other high-risk HPV types in cervical cancer, making it difficult to understand its contribution to cancerogenesis in infected women [23]. This may have implications on the effectiveness of vaccination strategies in HPV-35 prevalent regions, as the existing HPV vaccines do not target HPV-35.…”

Long-term follow-up on HIV infected and non-infected women with cervical cancer from Tanzania: staging, access to cancer-directed therapies and associated survival in a real-life remote setting

“…Screening included gynecological examination, speculum examination of the naive vagina and cervix uteri, and Visual Inspection using Acetic acid (VIA) on to the cervix uteri to identify aceto-white lesions suspicious for cervical intraepithelial dysplasia. In addition, samples for cytology and HPV-genotyping were taken from the ecto- and endocervix using an ayre’s spatula and a cytobrush, the results have been recently published [ 20 ]. In case of clinical cancer suspicion, biopsies were collected.…”