Improving Women’s Health: HIV, Contraception, Cervical Cancer and Schistosomiasis

Assessing the human rights violations women and girls face is critical to the successful implementation of recent scientific advancements. We will explore the opportunities of Sustainable Development Goal (SDG) initiatives to improve women’s health.

Invasive cervical cancer, caused by oncogenic genotypes of the human papillomavirus (HPV), is a leading cause of cancer-related morbidity and mortality among women worldwide. Over 85% of the global burden (over half a million new cases and quarter million deaths annually) is in low- and middle-income countries, most with concurrent high disease burdens due to human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Women with HIV have a higher risk for the development and progression of HPV-related neoplastic disease including cervical cancer. Over the past decade, millions of HIV-infected women globally are accessing affordable antiretroviral therapy and are now living long enough for HPV-induced cervical cancer to manifest and progress. Prevention interventions such as HPV vaccination and ‘screen-and-treat’ strategies offer unprecedented opportunities for reducing the burden of cervical cancer. Yet, the mere availability of these tools doesn’t automatically translate into their optimal utilization. Increasing efforts are being undertaken to innovatively expand cervical cancer prevention services for HIV-infected women in resource constrained settings. Such efforts include piggybacking on infrastructure developed via ongoing global health implementation programs like PEPFAR, task shifting to trained nurses with physician support by telemedicine, community mobilization and peer-to-peer support systems vital for broader community-level acceptance, and building and enhancing capacity for cancer treatment and management. Collaborative efforts that seek to optimize clinical care protocols and address key bottlenecks in implementation strategies are critical to guide the development and scaling up of cervical cancer prevention efforts for women living with HIV/AIDS in resource constrained settings.

Human immunodeficiency virus (HIV)-infected women carry a significant burden of human papillomavirus (HPV) infection and associated diseases. As HIV-infected individuals are living longer, the prevalence of HPV infection is rising and HPV-associated cytological abnormalities remain high despite successful treatments of HIV infection. Persistent infection with high-risk HPV causes squamous dysplasia and cancer of the cervix, and 40–90% of anal, vulvar, vaginal, penile, and oropharyngeal cancers. Over the last few years, focus has been placed on implementing primary preventive strategies, specifically vaccine development. There are three HPV vaccines licensed in the United States (U.S.), although currently only the nonavalent vaccine is available. In December 2014, a nonavalent HPV vaccine, Gardasil 9™, was approved for prevention of infection with the four HPV types in the quadrivalent vaccine and an additional five high-risk (HR) HPV types, 31, 33, 45, 52, and 58 (9v-HPV), increasing type-specific protection from 70% up to 90% of HPV types that cause cervical cancer. The quadrivalent HPV vaccine is safe and immunogenic in HIV-infected persons, and the 9v vaccine has been shown to have comparable immunogenicity rates to the quadrivalent vaccine for the four types found in both vaccines. Women infected with multiple anogenital HR-HPV types have lower rates of clearance than women infected with only one type. The majority of HR-HPV types detected in abnormal anogenital cytologies were types included in the 9v vaccine, and its use might impact the clearance rates of HR-HPV by decreasing the overall burden of anogenital HPV infection in HIV-infected women.

Tanzania is among the countries with the highest cervical cancer burden in East Africa; the leading cause of cancer related morbidity and mortality in women. Jhpiego with funding from USAID and Pink ribbon red ribbon partnered with the MoH to address the bottlenecks for women to access high quality cervical cancer screening services. Since 2010, Jhpiego has worked to build the foundation of a comprehensive cervical cancer prevention national program, and promoting a Single Visit Approach using visual inspection with acetic acid followed by treatment of precancerous lesions with cryotherapy or loop electrosurgical excision procedure. Advocacy meetings were held and the program worked with the MOH to develop technical policy documents (service delivery, advocacy, training package, QI, data tools, IEC materials), promoted task shifting and trained trainers and providers to have competence in screening and treatment, strengthened managers capacity and provided technical assistance to partners to scale up. The program reinforced new sites with supplies/equipment, conducted supervision and mentorship to improve quality of services, strengthened health information, maintenance of treatment machines and referral systems and worked to improve community and facility linkages. As a result; technical working group was formulated, technical documents and tools to guide effective implementation developed, 40 trainers equipped with skills to facilitate cervical cancer screening trainings, service providers trained in all Regions, progress review meetings conducted, 19 technicians equipped with maintenance skills of treatment machines and 577 sites established. A total of 57,304 new clients were screened, 7.4% had pre cancer lesions and 97% (3769) of women VIA positive lesions received same day treatment in 26 project sites. Experience has showed that improving coverage of cervical cancer screening using simple-effective technologies such as SVA is a worthwhile investment. MOH commitment, ensuring enabling environment, strengthening training and quality improvement system and working on long-term sustainability are key factors contributing to population coverage.

Advances in science, including bio-medical interventions around HIV prevention, treatment and care, treatment of opportunistic infections and HIV-related co-morbidities, have made huge strides in curbing the devastating impact of the HIV epidemic, and have offered hope for the end of AIDS as a public health threat. Nevertheless, new HIV acquisition among young women continues to outstrip that of their male counterparts; men’s access to testing and treatment services remains unacceptably low; and new prevention technologies – show mixed uptake and adherence, especially among adolescent girls and young women. It has been acknowledged that ‘we cannot treat ourselves out of the epidemic’. Affected communities face myriad barriers in accessing and utilizing biomedical services. Young women describe many health facilities as judgemental and “sex negative” spaces, where they are not able to freely discuss their HIV and SRHR needs. In health facilities and the community, young women living with HIV also face stigma and discrimination, violence, and gender inequality, which act as barriers to accessing information and health services. The routine exclusion of young women from spaces where decisions are made that affect their lives, results in many of these issues going unaddressed in the development and delivery of services. Participatory research with young women, the #WhatWomenWant campaign, and consultations with ZY+, have highlighted the problems young women most affected by HIV face; they also reveal the resilience, leadership potential and resourcefulness of young women. In order to maximize the benefits of science, delivery must be driven, owned and led by communities.

Worldwide, 266,000 women died of cervical cancer in 2012 — equivalent of one women dying every 2 minutes. 90% of these deaths were in low- and middle-income countries. Almost all of these deaths could be avoided if all adolescent girls were immunized against human papilloma virus (HPV) and cervical screening and treatment of pre-cancerous lesions were available to all women. To accelerate progress towards the elimination of this preventable disease, 7 UN agencies under the United Nations Task Force on NCDs have established a new 5-year Joint Programme to prevent and control cervical cancer. The Joint Programme provides global leadership as well as technical assistance to support governments and their partners to build and sustain high-quality national comprehensive cervical cancer control programmes. The Joint Programme brings together our joint efforts in taking new technologies to scale, reducing the costs of vaccines, and using innovative approaches to ensure women are accessing services, so that in a generation, death from cervical cancer ceases to be a public health issue.

The linkages between HIV and HPV have become more clear and visible. Due to evolving technological advancements we have been able to see a needed reduction in new infections in select parts of the world. However, these advances are fragmented and hampered by policy, funding and access barriers in many parts of the world where the most vulnerable and severely impacted women and girls call home. Despite the pronounced need to scale up both HIV, HPV and cervical cancer prevention, screening and treatment; many women and girls globally are still unaware of their risk and without access to these life-saving interventions. In the absence of inheritance rights, property rights, equitable pay and education, women and girls are far less equipped to refuse forced and coerced intercourse which reduces choice or autonomy and accelerates risk. This is coupled with the lack of access to quality sexual and reproductive health care, comprehensive sexuality education and tailored messaging; women and girls have another layer of blockade that limits health literacy and/or the ability to actively participate in a quality continuum of care. Additionally, the combined lack of political will and investments render inadequate health systems that scarcely acknowledge or provide services for HPV or cervical cancer. Effectively, sentencing women and girls to die because they are poor, lacking awareness and treated inequitably. Thus, we must urgently go beyond the bio-medical to expanding funding, igniting political will, promoting intersectional sexual and reproductive healthcare, developing innovative HIV, HPV and cervical cancer programming, and prioritizing gender equality to create enabling environments for healthy women and girls.

Empowering women and couples with the tools necessary to prevent unintended pregnancy and avoid sexually transmitted infections including HIV is critically important for individual and public health. Hormonal contraceptive methods are highly effective for prevention of unintended pregnancy and associated sequelae. However, some observational epidemiological studies have suggested an association between use of specific hormonal contraceptive methods [particularly depot medroxyprogesterone acetate (DMPA)] and an increased risk of HIV acquisition in women. This issue is critically important for women’s health, particularly in sub-Saharan Africa, where high rates of HIV coincide with high use of injectable contraception. Since all currently available data are observational, determining whether the association is causal is complex and has been controversial. This presentation will review the context and importance of this issue to global health, and will describe the methods and findings from systematic reviews which have synthesized the best available epidemiological data presently available on this etiologic question. Current global contraceptive guidance, as provided in the World Health Organization’s Medical Eligibility Criteria for Contraceptive Use, will be described. Finally, the presentation will explore what a potential increase in women’s HIV risk with use of DMPA would mean for individual women in contexts of high HIV prevalence, as well as considerations for policy makers grappling with this concern, using examples from published modeling data.

Worldwide, reproductive-aged women commonly use hormonal contraceptives to prevent pregnancy. Injectable hormonal contraceptives are particularly common and used by nearly 40% of reproductive-aged women in sub-Saharan Africa where HIV prevalence is high. Like all contraceptive methods, injectables can empower women and couples to achieve their reproductive goals, reduce unintended pregnancy, and prevent maternal morbidity and mortality. Concerning epidemiologic data suggest that women who use the most common type of injectable contraceptive, depot medroxyprogesterone acetate (DMPA), may have an increased risk of HIV acquisition compared to women not using contraception. The composite milieu of the female genital tract, including anatomic, immunologic, and microbiologic features, if exposed to HIV is likely critically important to determining HIV acquisition risk. This presentation will review the biological plausibility and current clinical evidence that use of contraceptive progestins may alter some or all of these genital tract features and thus impact HIV acquisition risk. The presentation will conclude with highlighting some of the key remaining research gaps in this area.

The ECHO trial is an open-label, randomised clinical trial comparing HIV incidence and contraceptive benefits in women using depot medroxyprogesterone acetate (DMAP), levornogestrel (LNG) implant, and the copper intrauterine device (IUD). Observational studies suggest that some contraceptive methods (particularly the injectable methods DMPA) could increase HIV susceptibility in women. However, the data is not definitive, policy has not changed and we do not have evidence on whether alternative methods may be better. Given the widespread use of DMPA in areas of high HIV incidence, the question of whether DMPA increases women’s risk of HIV is a critical public health issue requiring the strongest evidence ECHO Study. During this presentation, I’ll discuss the ECO trial design and the different plausible outcomes from the ECHO trial.

At least 240 million people require treatment to prevent morbidity caused by schistosomiasis. Schistosoma haematobium, urogenital schistosomiasis, is a largely African, waterborne, parasitic disease that may cause Female Genital Schistosomiasis (FGS). Once inside the body of a human, the worms may lay eggs that may be excreted in urine or may be deposited in the urogenital organs where they cause damage for decades after exposure. The symptoms of FGS start in childhood and may mimic sexually transmitted infections and cancer, with contact bleeding and discharge. Children as young as 10 years of age have intravaginal lesions, malodorous discharge, bloody discharge, a burning sensation in the genitals and ulcers. They grow into adulthood with damaged genitals. In the first study on FGS and HIV Zimbabweans with FGS were found to have a 3-fold higher odds-ratio of HIV infection. When investigated by a clinician four lesions may be found: (1) Grainy sandy patches appearing as single grains and clusters of grains. Each grain represents an egg. (2) Homogenous yellow patches (3) Rubbery papules (4) Abnormal blood vessels, often accompanied by bleeding. Lesions may be located on the cervix or on the vaginal wall and constitute viable S. haematobium eggs, calcified remains of old eggs and immunological cells with disproportionally high number of the HIV receptor CCR5. FGS lesions are equally prevalent in all adult age groups. Currently FGS is not diagnosed in clinical practice. Further research is needed to determine if HIV can be prevented by treating FGS.

A growing body of evidence contributes to our understanding of the relationship between schistosomiasis and HIV infections. Multiple prevalence studies conducted in sub-Saharan Africa have found that women, but not men, who have chronic schistosome infections may be at higher risk of HIV acquisition. Macaque studies also have shown that Schistosoma mansoni infection may increase susceptibility to HIV infection and increase HIV-1 RNA viral load levels in those who become HIV-infected. Mouse models demonstrate that schistosome infections shift host immunity towards a T-helper (Th)-2 predominant state and away from antiviral cytolytic T-helper (Th)-1 immune responses, permitting viral replication and reactivation. A recent longitudinal study in Tanzania, conducted in an area with endemic S. mansoni infection, demonstrated a 2.8-fold increased odds of HIV-1 acquisition in women who had pre-existing schistosome infections as compared to women who did not. The odds of HIV acquisition was not increased in men with schistosome infections. In both sexes, the HIV-1 RNA viral load was higher in people who had had active schistosome infection at the time of HIV-1 seroconversion than in those who had been schistosome-uninfected. Taken together, these studies suggest that interactions between HIV-1 and schistosomiasis may play a critical role in HIV-1 transmission and disease progression in African countries where schistosome infections are concentrated. They also underscore the importance of considering host sex in studies of HIV and schistosome infections. Additional studies to validate these findings and to determine the effectiveness of treating schistosome infections as an HIV prevention strategy are urgently needed.

Schistosomiasis is an infectious disease that affects more than 230 million people worldwide, of whom 90% are in Africa. Schistosome infection usually occurs in childhood with freshwater contact and recurrent exposures throughout the lifespan. In some regions, particularly sub-Saharan Africa, the epidemics of HIV and schistosomiasis closely overlap; communities with the highest burden of schistosomiasis also have high HIV prevalence. Furthermore, endemic schistosomiasis, specifically female genital schistosomiasis (FGS), which affects 19 million girls, may increase risk of HIV infection, particularly among adolescent girls and young women (AGYW). FGS, caused by Schistosoma haematobium, causes mucosal changes in the vaginal epithelium and alters host immune response, rendering women at high risk of infertility and potentially, HIV acquisition. The association of schistosomiasis, specifically FGS, with increased HIV acquisition is biologically plausible but research has been suboptimal. Research is needed to understand the effect of FGS and its treatment on HIV acquisition, particularly among AGYW. Furthermore, studies are necessary to understand whether the increased risk of HIV acquisition is substantial enough to warrant offering pre-exposure prophylaxis for HIV among AGYW with FGS and whether treatment of FGS affects the risk of HIV acquisition. This presentation will summarize the currently available evidence of the association between HIV and schistosomiasis, highlighting recent studies, and discuss clinical issues particularly relevant to HIV-infected persons. The presentation will also highlight priorities for future research.