2H study

A case-control study to identify risk factors associated with Human Papilloma Virus (HPV) associated lesions within the female reproductive tract

Cervical cancer, which is caused by persistent infection by High Risk HPV types, is the most frequent cancer in Tanzanian females, particularly affecting those co-infected with HIV. This study investigates risk factors associated with high-grade squamous intraepithelial lesion (HSIL) or squamous cell carcinoma (SCC) within the reproductive tract of Tanzanian women and identify High Risk (HR) HPVs that most frequently cause such disease in HIV +ve and HIV -ve women. This study focuses on HPV and HIV related factors, particularly on infecting HPV genotype(s) and immune system related factors, such as CD4 T-cell count, antiretroviral therapy (ART) status and HIV induced dysfunction of HPV-specific adaptive immunity. In addition, quality of life for cancer patients and socio-economic factors  (such as sexual behaviour, age and smoking) will be studied.

A longitudinal follow up of selected HIV +ve and HIV -ve 2H study participants will allow to study viral persistence and clearance rates, and lesion recurrence after treatment of precancerous lesions. Highly Active Antiretroviral Treatment (HAART) associated reconstitution of HPV-specific immunity will be studied in relation to viral clearance and disease progression in HIV +ve 2H study participants initiating HAART. 

A maximum of 600 adult women will be enrolled in four groups: 100 HIV positive and 100 HIV negative women with HSIL/SCC (Cases); 200 HIV positive and 200 HIV negative women with no cytological abnormalities or lower grade lesions (ASCUS, LSIL) will be enrolled as controls. 

The anticipated results of this study will provide the basis for rational improvement of immunotherapeutic interventions in a patient population most heavily affected by HPV associated cancers and precancerous lesions. 

Team: 

Principal Investigator: Christof Geldmacher, PhD, University of Munich (LMU)

Co-Principal Investigator: Dr. Arne Kroidl, MD, University of Munich (LMU)

Site Principal Investigator: Dr. Leonard L. Maboko, MD, MSc, PhD, (NIMR-MMRC)

Investigators: Dr. Tessa Lennemann, MD, (LMU); Dr. Mkunde Chachage, PhD, (NIMR-MMRC); Dr. Asli Bauer, PhD (LMU); Dr. Ruby Mcharo, MD, MPH-IH, (NIMR-MMRC); Dr. Liset Torres, MD, MSc, (MRH); Dr. John France, MD, MSc, (MRH).

Objective / Purpose:

Primary Objective

1. Identification of frequent HR HPV types associated with a high risk of High grade Squamous Intraepithelial lesions or Squamous cell carcinoma in HIV+ and HIV- women.

Secondary Objectives

1. Describe HIV related and non HIV related potential risk factors associated with HSIL or Squamous cell carcinoma. 

2. Study of in situ immune infiltrates into lesions and peripheral adaptive immune responses in relation to high grade lesion (case) versus low grade/healthy (control) and in relation to HIV infection (HIV+ versus HIV- subjects) 

3. Compare different methods for the detection of cervical intraepithelial lesions (VIA, cytology/histology, HPV diagnostics)

4. Determine treatment outcome of HPV-associated lesions after therapeutic intervention as well as viral clearance/persistence

5. Study HPV viral persistence and clearance rates in clinical asymptomatic women previously not in need of therapeutic intervention and the related clinical relevance

6. Study HPV viral persistence and clearance rates in relation to HIV and HAART status or initiation.

7. Identification of frequently recognized antigenic regions by T cells within E6 and E7 for 5 most medically relevant HPV types.

8. Compare different levels of service delivery and different approaches to scale out cervical carcinoma screening

9. Follow up on patients diagnosed with cervical carcinoma (interventions, quality of life, mortality)

Research strengthening and capacity building objectives

Apart from the above mentioned scientific objectives, the study will also serve to

1. Establish clinical research infrastructure for cervical carcinoma clinical studies and HPV vaccine trials.

2. Implement a continuous scientific training program (workshops) for MMRP and MRH scientific and laboratory staff and other East African Researchers. 

3. Conduct a workshop on HPV-HIV co-pathogenesis for involved scientific and laboratory staff and other East African Researchers. 

 

Methods / Approaches:

Population to be screened: HIV positive and HIV negative women attending the Cervical Carcinoma Screening at the Mbeya Referral Hospital (MRH) HIV Care and Treatment Centre (CTC), at the META Gynecological Outpatient Department of the Mbeya Referral Hospital, as well as sites providing Cervical Carcinoma Screening within Mbeya Region including the MMRC Mobile Diagnostic and Treatment Service (MDTC).

Progress / future plans:

As of February 2015, a total of more that 1200 women have been screened in the 2H study.

Sponsors:

DFG (Deutsche Forschungsgemeinschaft): a German research foundation.

 

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