Background The burden of HPV-associated premalignant and malignant cervical lesions remains high in HIV+ women even under ART treatment. In order to identify possible underlying pathophysiologic mechanisms, we studied activation and HIV co-receptor expression in cervical T-cell populations in relation to HIV, HPV and cervical lesion status. Methods Cervical cytobrush (n = 468: 253 HIV- and 215 HIV+; 71% on ART) and blood (in a subset of 39 women) was collected from women in Mbeya, Tanzania. Clinical data on HIV and HPV infection, as well as ART status was collected. T cell populations were characterized using multiparametric flow cytometry-based on their expression of markers for cellular activation (HLA-DR), and memory (CD45RO), as well as HIV co-receptors (CCR5, α 4 β 7 ). Results Cervical and blood T cells differed significantly, with higher frequencies of T cells expressing CD45RO, as well as the HIV co-receptors CCR5 and α 4 β 7 in the cervical mucosa. The skewed CD4/CD8 T cell ratio in blood of HIV+ women was mirrored in the cervical mucosa and HPV co-infection was linked to lower levels of mucosal CD4 T cells in HIV+ women (%median: 22 vs 32; p = 0.04). In addition, HIV and HPV infection, and especially HPV-associated cervical lesions were linked to significantly higher frequencies of HLA-DR+ CD4 and CD8 T cells (p-values < 0.05). Interestingly, HPV infection did not significantly alter frequencies of CCR5+ or α 4 β 7 + CD4 T cells. Conclusion The increased proportion of activated cervical T cells associated with HPV and HIV infection, as well as HPV-associated lesions, together with the HIV-induced depletion of cervical CD4 T cells, may increase the risk for HPV infection, associated premalignant lesions and cancer in HIV+ women. Further, high levels of activated CD4 T cells associated with HPV and HPV-associated lesions could contribute to a higher susceptibility to HIV in HPV infected women.

Background Worldwide 85% of cervical cancer (CC) related deaths occur in low- and middle-income countries. Sub-Saharan Africa is burdend by an overlapping high incidence of CC as well as HIV infection, a risk factor for HPV associated disease progression. Recent upscaling of CC screening activities increased the number of CC diagnoses in a previous unscreened population. The aim of the 2H study was to follow up on women with CC in the context of available health care services in Tanzania in relation to their HIV infection status. Methods This longitudinal observational cohort study included women with histological confirmed CC from Mbeya, Tanzania, between 2013–2019. All women were referred for CC staging and cancer-directed therapies (CDT), including surgery and/or radio-chemotherapy, or palliative care. Annual follow-up focused on successful linkage to CDT, interventions and survival. We assessed factors on compliance, used Kaplan–Meier-Survivor functions to evaluate survival time and poisson regression models to calculate incidence rate ratios on mortality (IRR) two years after diagnosis. Results Overall, 270 women with CC (123 HIV infected) were included. Staging information, available in 185 cases, showed 84.9% presented with advanced stage disease (FIGO ≥ IIB), no difference was seen in respect to HIV status. HIV-infected women were 12 years younger at the time of cancer diagnosis (median age 44.8 versus 56.4 years, p < 0.001). Median follow up period was 11.9 months (range 0.2–67.2). Survival information, available in 231 cases, demonstrated for women diagnosed in early-stage disease a median survival time of 38.3 months, in advanced-stage 16.0 months and late-stage disease 6.5 months after diagnosis. Of all women, 42% received CDT or palliative support. HIV co-infection and education were associated with higher health care compliance. CDT was significantly associated with lower 2-year mortality rates (IRR 0.62, p = 0.004). HIV coinfection did not impact mortality rates after diagnosis. Conclusion High numbers of advanced and late staged CC were diagnosed, compliance to CDT was low. A beneficial impact of CDT on CC mortality could be demonstrated for local health care services. This study indicates challenges for successful linkage and supports an effective scale up of cancer care and treatment facilities.

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.

Background Sexual and reproductive health (SRH) among young adults in low- and middle-income countries (LMIC) is still a major public health challenge. Early school-based sexuality education programs and sexual health information sharing between teachers, parents and young people have been considered protective against the sexual health risks to which young people are exposed. There is, however, limited information on the preferred choices of “where”, “how” and “from whom” young people would like to receive SRH information. We aimed to describe the experience and preferences of young people regarding their SRH education and learning and in particular communication with their parents/guardians. Methods We conducted a cross-sectional study among randomly selected students aged 18-24y attending Higher Learning Institutions (HLIs) in Mbeya, Tanzania. We used a self-administered questionnaire to collect information on SRH education received, ability to discuss SRH matters with a parent/guardian and SRH information gaps encountered during their early sexual experience. Results We enrolled 504 students from 5 HLIs, of whom 446 (88.5%) reported to be sexually active, with mean age at sexual debut of 18.4y (SD 2.2). About 61% (307/504) of the participants found it difficult to discuss or did not discuss SRH matters with their parent/guardian while growing up. Learning about SRH matters was reported from peers (30.2%) and teacher-led school curriculum (22.7%). There was a strong gender-biased preference on SRH matters’ discussions, female and male participants preferred discussions with adults of their respective sex. Peers (18.2%), media (16.2%) and schools (14.2%) were described as the preferred sources of SRH information. On recalling their first sexual experience, sexually-initiated participants felt they needed to know more about sexual feelings, emotions and relationships (28.8%), safer sex (13.5%), how to be able to say ‘No’ (10.7%) and how to use a condom correctly (10.2%). Conclusion Young people have a gender preference when it comes to learning about SRH matters from their parents; however, such conversations seldom occur. Community health education should focus on building skills of parents on parent-child communication on SRH matters so as to empower them to confidently initiate and convey accurate SRH information. Comprehensive SRH education and skills building need to be strengthened in the current school SRH curriculum in order to meet the demand and needs of students and increase the competence of teachers.

BackgroundCervical cancer - caused by persistent High Risk Human Papilloma Virus (HR HPV) infections - is the second most common cancer affecting women globally. HIV infection increases the risk for HPV persistence, associated disease progression and malignant cell transformation. We therefore hypothesized that this risk increase is directly linked to HIV infection associated dysfunction or depletion of HPV-oncoprotein-specific T-cell responses.MethodsThe 2H study specifically included HIV+ and HIV- women with and without cervical lesions and cancer to analyze HPV oncogene-specific T cell responses in relation to HPV infection, cervical lesion status and HIV status. Oncoprotein E6 and E7 specific T-cell responses were quantified for the most relevant types HPV16, 18 and 45 and control antigens (CMV-pp65) and M.tb-PPD in 373 women, using fresh peripheral blood mononuclear cells in an IFN-γ release ELISpot assay.ResultsOverall, systemic E6- and E7-oncoprotein-specific T-cell responses were infrequent and of low magnitude, when compared to CMV-pp65 and M.tb-PPD (p &lt; 0.001 for all HR HPV types). Within HIV negative women infected with either HPV16, 18 or 45, HPV16 infected women had lowest frequency of autologous-type-E6/E7-specific T-cell responses (33%, 16/49), as compared to HPV18 (46% (6/13), p = 0.516) and HPV45 (69% (9/13), p = 0.026) infected women. Prevalent HPV18 and 45, but not HPV16 infections were linked to detectable oncoprotein-specific T-cell responses, and for these infections, HIV infection significantly diminished T-cell responses targeting the autologous infecting genotype. Within women living with HIV, low CD4 T-cell counts, detectable HIV viremia as well as cancerous and precancerous lesions were significantly associated with depletion of HPV oncoprotein-specific T-cell responses.DiscussionDepletion of HPV-oncoprotein-specific T-cell responses likely contributes to the increased risk for HR HPV persistence and associated cancerogenesis in women living with HIV. The low inherent immunogenicity of HPV16 oncoproteins may contribute to the exceptional potential for cancerogenesis associated with HPV16 infections.

Background High-risk sexual behaviors(HRSBs) among young adults are key risk for Sexually Transmitted Infections(STIs), HIV and unplanned pregnancies. WHO has identified the 15-24years age-group as high-risk for STIs. Students at Higher Learning Institutions(HLIs) may be at higher risk because they are free of immediate parental-supervision, are a transient migratory population, probably at peak-years of sexual activity.  In Tanzania, information is limited on sexual and preventive behaviours among young adults in HLIs. We describe risky sexual behaviours and preventive practices among young adults attending HLIs in Mbeya-Tanzania. Methods We conducted a cross-sectional study from March2019 to January2020 among randomly selected students aged 18-24years enrolled in HLIs within Mbeya.  Probability proportional to size was used to determine total student number from each HLI. We used a self-administered questionnaire to collect information on sexual health education, activity, behaviour and STI knowledge. Results Total of 504students were enrolled with mean age of 21.5(SD 1.74)years. Total of 446(88.5%) students reported ever having had sex. Mean-age at first sex was 18.4years and 9.9% reported sexual debut <15years. A higher proportion of male students(57%) reported sexual debut with non-steady partners than females(37.9%). Lack of condom use at sexual debut was reported by 52% of the participants. Consistent condom use during past 4-weeks was reported at 33% and 16.5% among males and females, respectively. About 1 in 10 students reported forced sex by someone they were dating. Sex under the influence of alcohol was reported by 24% of the students.  Nearly 8 in 10 (78.7%) students have heard of STIs, but only 16% were aware STIs can be asymptomatic.  Conclusion STI prevention programs need to recognize young adults in HLIs as at-risk population; and advocate targeted messages to minimize risk to acquiring STIs, counseling and support for those experiencing sexual violence, promote condom use and safer-sex negotiation skills.

Background: High-risk sexual behaviours (HRSBs) among young adults are a key risk for Sexually Transmitted Infections (STIs), HIV and unplanned pregnancies. The World Health Organization has identified the 15-24 year age-group as high-risk for STIs. Students at Higher Learning Institutions (HLIs) may be at higher risk because they are free of immediate parental supervision, a transient migratory population, and probably at peak years of sexual activity. Here, we describe risky sexual behaviours and preventive practices among young adults attending HLIs in Mbeya, Tanzania. Methods: Cross-sectional study was conducted from March 2019 to January 2020 among students aged 18-24 years enrolled in HLIs within Mbeya. A self-administered questionnaire was used to collect information on sexual health education, activity, behaviour and STI knowledge. Results: 504 students were enrolled; mean age of 21.5 (SD 1.74) years. 377 (74.8%) students were sexually active. Mean age of first sexual encounter was 18.4 years and 11.6% reported their sexual debut was <15 years. A higher proportion of male students (59.7%) reported their sexual debut with non-steady partners compared with female students (40.9%). Lack of condom use at sexual debut was reported by 43.3% of sexually active students. Consistent condom use during the past 4-weeks was reported at 23.3% and 16.9% among men and women, respectively. Almost 1 in 10 students reported being forced into having sex by someone they were dating. Sex under the influence of alcohol was reported by 25.5% of the students. Nearly 7 in 10 (77%) students had heard of STIs, but only 15% were aware STIs could be asymptomatic.  Conclusion: STI prevention programs need to recognize young adults in HLIs as an at-risk population. HLIs must advocate targeted messages to minimize risks to acquiring STIs, offer counselling and support for those experiencing sexual violence, and promote condom use and safer-sex negotiation skills.

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