Secondary Cervical Cancer Prevention of Vulnerable Women With HPV and HIV Co-infection in India

Summary

Cervical cancer (CC) remains one of the most common malignancies among women in India, with nearly 100,000 women diagnosed annually and over 60,000 preventable deaths annually. With high-risk human papillomavirus (HR-HPV) as the causative agent for CC, one risk factor that places women at high risk for CC is human immunodeficiency virus (HIV), as impaired immune response against Human papillomavirus (HPV) may result in persistent HR-HPV infection, a critical risk factor for progression of HPV-related cervical oncogenesis. Progression of precancerous lesions among women living with HIV (WLH) is also associated with: 1) lack of HPV screening; 2) high levels of depressive symptoms and stigma; and 3) malnutrition, which negatively impacts the activation and proliferation of immune cells. Yet programs that offer WLH with comprehensive services focused on HPV screening and psychological and nutritional support are almost non-existent, and the gap is critical. Nutrition plays an integral role in relationship to HPV/HIV co-infection, as demonstrated by an increased risk of HR-HPV associated with poor nutrition; nutritional deficiencies are likewise linked to cervical intra-epithelial neoplasia. The immunological effect of malnutrition may also be exacerbated among WLH due to elevated energy demands of chronic immune activation; worsened with HPV/HIV co-infection. Further, depressive symptoms (aka depression for brevity) partially mediate the effect of food insecurity on HIV viral suppression. In our completed ASHA-Nutrition R01 study of antiretroviral (ART) adherence, the investigators trained lay community health workers, named Accredited Social Health Activist (ASHA), to improve the health of 600 rural WLH by providing emotional support, skill-building, nutrition education, and/or protein-enriched food supplements. In that study, our intervention, co-delivered by our trained ASHA, and guided by nurses, led to increased CD4+ T cell recovery and improved anthropometric and psychosocial outcomes. The investigators found that ASHA support plus protein supplements and nutritional education were significantly associated with improved CD4 counts and increased lean mass at 18 months (P \< 0.001), as well as significant improvements in depression, ART adherence, social support and internalized stigma. In our sub study, CC screening of 598 of these WLH revealed that 13% were found to have abnormal cervical lesions and 4 (1%) had squamous CC. Preliminary evidence also revealed that nutritional supplements may be associated with a 40% reduction in the risk of abnormal cervical lesions (adjusted odds ratio \[aOR\] = 0.60), with an association between serum albumin and reduced risk of abnormal lesions (aOR= 0.39).

With a focus on secondary prevention of CC, the investigators hope to mitigate the link between HR-HPV persistence and risk of CC as well as improve the health of women co-infected with HPV/HIV (W-Co-V). Our stellar team plans to build upon our prior ASHA-Nutrition intervention, using formative research to refine a nurse-led, ASHA co-delivered, nutrition-enhanced ASHA-Health HPV intervention, adapted for W-Co-V. This will be followed by a randomized controlled trial (RCT), assessing the efficacy of our refined comprehensive, multifaceted ASHA-Health HPV intervention, as compared with an enhanced Standard of Care (SOC+) (usual care + 3 sessions \[wellness, basic nutrition and HPV/HIV health promotion\]) among 420 high-risk co-infected women to prevent CC while remaining engaged in the HIV treatment cascade, and managing nutritional health. Participants, recruited from a total of 24 villages, will be individually randomized in a 1:1 ratio into the two study arms. Our Primary outcome is HR-HPV persistence (2 positive tests for the same HR-HPV type, separated by 12-18 months). The two aims incorporating RCT interventions are as follows:

Aim 2. To evaluate the efficacy of ASHA-Health HPV intervention among 420 W-Co-V on the primary outcome (HR-HPV persistence) as compared to the Enhanced Standard of Care (SOC+) program. H2: Compared to the SOC+ participants, ASHA-Health participants will have lower rates of HR-HPV persistence.

Aim 3. Assess the impact of the ASHA-Health program secondarily on: 1) HIV indices (HIV viral load; CD4 count); 2) Nutritional index (serum albumin) at 6-, 12-, and 18-months.

Conditions

• Cervical Cancer
• Human Papillomavirus (HPV) Infection
• Human Immunodeficiency Virus (HIV) Infection

Interventions

BEHAVIORAL

ASHA-Health HPV Intervention

The ASHA-Health HPV program will include three components: 1) Individual 1:1 weekly ASHA support; 2) 8 group sessions for the 42 W-Co-V in the ASHAHealth cohort, covering content in Modules 1-4; and 3) referral to life skills classes. The assigned ASHA will provide services to support the W-Co- V in accessing and/or adhering to HPV and ART appointments (arrange transportation, provide counseling, promote healthy lifestyle choices, and link with community resources). ASHA will also promote positive coping, social support, and aid in dealing with stigma. The 8 group sessions will be held over the six months, based on the needs identified by the women. Overall, the intervention content targets the provision of emotional support, skill building, HPV/ HIV and nutrition education, and protein-enriched food supplements, and ways to deal with stress, stigma, and the importance of engagement and retention in care. Food selections will be guided by our nutrition experts.

BEHAVIORAL

Enhanced Standard of Care (SOC+)

Selecting our base at the Belgaum ART Centers will provide the most up to date services for the SOC+ group. Yet, there is no typical standard of care in India as it relates to HPV screening for W-Co-V and stigma associated with both diseases is high. Further, in India, screening services are lacking at most ART centers. Since it would be unethical to withhold potentially lifesaving information about HPV, the investigators will offer an enhanced standard of care to include usual care + 3 (1.5 hour) group sessions on wellness, basic nutrition, coping with mental health issues, and HIV/ HPV information. Thus, women will meet as a group three times over the six-month period. In addition, the women have access to our SOC+ nurse and ASHA to respond to questions.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• University of California, San Francisco

  collaborator OTHER

• National Institute of Mental Health and Neuro Sciences (NIMHANS)

  collaborator UNKNOWN

• University of California, Irvine

  lead OTHER

Principal Investigators

• Adey Nyamathi, ANP, PhD, FAAN · UCI Sue & Bill Gross School of Nursing

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

25 Years

Max Age

50 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-02-01

Primary Completion

2029-08-31

Completion

2030-07-31

Countries

• India

Study Locations