HIV and Other Risk Factors for Esophageal Squamous Cell Carcinoma in Malawi

January 5, 2023 updated by: UNC Lineberger Comprehensive Cancer Center

LCCC 1608 - HIV and Other Risk Factors for Esophageal Squamous Cell Carcinoma in Malawi

The primary purpose of this single-center, case-control, non-interventional study is to determine risk factors which contribute to the development of esophageal squamous cell carcinoma (ESCC) at Kamuzu Central Hospital (KCH) and St. Gabriel Hospital (SGH) in Malawi.

Study Overview

Status

Completed

Conditions

Detailed Description

RATIONALE FOR RESEARCH

The Rift Valley of Africa is a 'hot spot' for ESCC, yet little is known about the etiology of this disease in Sub-Saharan Africa. In Malawi, ESCC is the third commonest cancer nationwide behind Kaposi sarcoma and cervical carcinoma. Among cancers that are not classically HIV-related, ESCC has the highest incidence in Malawi. The ESCC burden recorded in the national cancer registry is also likely an underestimate, as many cases may go undiagnosed and unregistered. Additionally, few data are available on the epidemiology of ESCC in Malawi, and underlying reasons for high frequency of the disease are largely unknown. This knowledge gap is a major barrier to public health prevention efforts. Given that survival after ESCC diagnosis is dismal in Malawi (12% at 1 year), developing evidence-based prevention efforts is paramount.

The proposed study will make a significant contribution to existing literature from Malawi and Sub-Saharan Africa in several important respects. First, previous epidemiologic studies of ESCC in Malawi have been limited by challenges with appropriate control selection, which may have limited the validity of their findings. Secondly, our study will include prospective clinical follow-up of confirmed ESCC cases as they receive treatment under local conditions to provide accurate survival estimates. Thirdly, biospecimens from consenting patients will permit etiology and pathogenesis studies to understand mechanisms of ESCC development, which can be correlated with high-quality clinical and epidemiologic data. Finally, we plan to coordinate with other ESCC researchers in eastern and southern Africa to harmonize data collection, and help create a regional consortium in which Malawi can be a founding member and active participant.

Primary Objective: Identify demographic and environmental risk factors for ESCC through a case-control study implemented at KCH and SGH. Hypothesis: Modifiable risk factors contribute significantly to ESCC. These include polycyclic aromatic hydrocarbon (PAH) exposure from various sources, excessively hot beverages, dietary factors such as maize fumonisin and low selenium, and HIV infection.

Secondary Objective: Identify common genetic and epigenetic alterations in germline and somatic DNA associated with ESCC development. Hypothesis: Recurring genetic and epigenetic alterations can facilitate risk stratification, development of early detection biomarkers, and identification of novel treatment strategies.

Procedures

After informed consent and study enrollment, subjects will be interviewed using a structured questionnaire and provide biological samples including saliva, blood, urine, and toenail clippings. Esophageal biopsies will be taken for diagnostic confirmation and to support molecular studies. If patients suspected to have ESCC are enrolled but then pathologically confirmed to have an alternate diagnosis, they will be withdrawn. HIV testing will be offered to all participants, and CD4, HIV RNA, and ART status documented for HIV-infected participants. Exposures will be measured using the questionnaire and laboratory analyses of saliva, blood, urine, and toenail samples. We will collect information on: demographic characteristics; HIV status; tobacco and drug use; alcohol consumption; medical history; family history of cancer; indoor air pollution; occupational history; diet, cooking, and food preservation; beverage history including temperature; farming; signs and symptoms of upper gastrointestinal disease; oral health; anthropometric indices; and reproductive history. To examine correlates with patient outcomes, telephone follow-up to assess vital status will be done every 3 months until 2 years from enrollment. Biological samples will be stored in freezers and transferred to the US only for assays that are currently unavailable in Malawi. Laboratory testing will include serum selenium level, blood and urine testing for PAH exposure, tumor immunohistochemistry assays, salivary DNA isolation for genetic studies, and molecular profiling of ESCC tumors.

Analysis

Sample size will include 300 ESCC cases and 300 controls; 66-68 case control pairs will be enrolled per year, over 3 years, assuming a response rate of 75% in the endoscopy clinic. With 300 case-control pairs, estimated statistical power for an exposure with control population prevalence of 10% and OR 2.0 is 81%, using alpha level 0.05, with higher power for higher control exposure rates and odds ratios. Expected prevalence for key exposures (tobacco and alcohol, hot tea, PAH exposure, selenium deficiency, HIV) is 10-50% in the control population. To assess epidemiologic risk factors for ESCC, we will use logistic regression to estimate odds ratios and 95% confidence intervals for each exposure, while controlling for possible confounders. Survival estimates will be generated using Kaplan-Meyer curves to estimate overall survival at 6, 12 and 24 months.

Study Type

Observational

Enrollment (Actual)

600

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Malawi
      • Lilongwe, Malawi
        • UNC Project
      • Lilongwe, Malawi
        • UNC Project, Lighthouse Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

300 cases diagnosed with histologically confirmed ESCC and 300 patient controls without a history of esophageal cancer or esophageal squamous dysplasia, a history of other cancer, or upper gastrointestinal diseases, 18 years, and older, male/female in Malawi.

Description

Inclusion Criteria:

  • Cases Inclusion Criteria

    • All patients > 18 years of age diagnosed with histologically confirmed ESCC are eligible to be a case regardless of sex or place of residence.
    • Diagnosis of ESCC (histologically confirmed)
    • Subject able to understand and provide written consent in English or Chichewa
    • Able to understand and comply with study procedures for the entire length of the study

Controls Inclusion Criteria

  • All patients > 18 years of age without a history of esophageal cancer or esophageal squamous dysplasia, a history of other cancer, or upper gastrointestinal diseases are eligible to be controls, regardless of age, sex, or place of residence
  • Subject able to understand and provide written consent in English or Chichewa
  • Able to understand and comply with study procedures for the entire length of the study

Exclusion Criteria:

  • Cases Exclusion Criteria

    • Healthcare provider determines it is unsafe to perform a biopsy
    • Mental impairment which precludes provision of informed consent
    • Patients who are unable to provide their past medical history

Controls Exclusion Criteria

  • All patients > 18 years of age with a history of esophageal cancer or esophageal squamous dysplasia, a history of other cancer, or upper gastrointestinal diseases are ineligible to be controls
  • Patients with significant difficulty swallowing
  • Mental impairment which precludes provision of informed consent
  • Patients who are unable to provide their past medical history

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
300 esophageal cases
diagnosed with histologically confirmed ESCC
300 patient controls
without a history of esophageal cancer or esophageal squamous dysplasia, a history of other cancer, or upper gastrointestinal diseases

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Risk factors for ESCC - HIV Infection
Time Frame: 2 years
To identify risk factors for ESCC through a case-control study implemented at a national teaching hospital, specifically focused on the following exposures: HIV infection, PAH exposure, Dietary factors including fumonisin and selenium, Scalding hot beverages and foods, Tobacco and alcohol consumption
2 years
Survival estimates after ESCC diagnosis in Malawi.
Time Frame: 2 years
To assess survival after ESCC diagnosis in Malawi.
2 years
Risk factors for ESCC - HIV Infection
Time Frame: 2 years
To identify risk factors for ESCC through a case-control study implemented at a national teaching hospital, specifically focused on the following exposures: HIV infection
2 years
Risk factors for ESCC - PAH exposure
Time Frame: 2 years
To identify risk factors for ESCC through a case-control study implemented at a national teaching hospital, specifically focused on the following exposures: PAH exposure
2 years
Risk factors for ESCC - Dietary factors including fumonisin and selenium
Time Frame: 2 years
To identify risk factors for ESCC through a case-control study implemented at a national teaching hospital, specifically focused on the following exposures: Dietary factors including fumonisin and selenium
2 years
Risk factors for ESCC - Scalding hot beverages and foods,
Time Frame: 2 years
To identify risk factors for ESCC through a case-control study implemented at a national teaching hospital, specifically focused on the following exposures: Scalding hot beverages and foods
2 years
Risk factors for ESCC - Tobacco and alcohol consumption
Time Frame: 2 years
To identify risk factors for ESCC through a case-control study implemented at a national teaching hospital, specifically focused on the following exposures: Tobacco and alcohol consumption
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The common somatic genetic and epigenetic alterations in ESCC tumors from Malawi.
Time Frame: 2 years
To identify and characterize common somatic genetic and epigenetic alterations in ESCC tumors from Malawi.
2 years
The germline genetic and epigenetic alterations associated with susceptibility to ESCC.
Time Frame: 2 years
To identify and characterize germline genetic and epigenetic alterations associated with susceptibility to ESCC.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UNC Lineberger Comprehensive Cancer Center

Investigators

  • Principal Investigator: Satish Gopal, MD, MPH, UNC-CH

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 26, 2017

Primary Completion (Actual)

December 31, 2022

Study Completion (Actual)

December 31, 2022

Study Registration Dates

First Submitted

May 4, 2017

First Submitted That Met QC Criteria

May 17, 2017

First Posted (Actual)

May 19, 2017

Study Record Updates

Last Update Posted (Estimate)

January 6, 2023

Last Update Submitted That Met QC Criteria

January 5, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LCCC 1608

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Esophageal Squamous Cell Carcinoma

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in United States

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe