Transcript bongani-kailmila-unc-hiv-and-other-risk-factors-for

HIV and Other Risk Factors for
Esophageal Squamous Cell
Carcinoma in Malawi
Bongani Kaimila
Malawi Cancer Symposium
30th August 2016
Background
• Esophageal cancer is the 6th leading cause of cancer globally
• 400,000 deaths annually1
• Majority of cases are Squamous Cell Carcinoma (ESCC), fewer cases
are Adenocarcinoma
• Occurs in ‘geographical hotspots’ 2
• East and Southern Africa is a hotspot
Rationale
• ESCC third commonest cancer in Malawi3
• Commonest among classically non-HIV associated cancers
• Very high case fatality (12% one year survival)4
• Epidemiology of ESCC in Malawi poorly understood
Literature review
• Kayamba et al (Zambia): HIV infection and indoor smoke exposure are
associated with increased risk for ESCC. Relationship between HIV
and ESCC not demonstrated elsewhere. Mlombe et al (Malawi):
demonstrated increased risk of ESCC with indoor smoke exposure.
• Kamangar & Lubin et al (South America): High levels of Poly Aromatic
Hydrocarbon (PAH) exposure associated with Esophageal cancer.
Replicated in Kenya (Dawsey et al).
Literature review
• Jesri et al (Iran): dietary micronutrient deficiency and increased risk
for ESCC
• Sun et al (China): high Fumonisin B1 toxin in maize and ESCC high risk
areas
• Munishi et al (Kenya and Tanzania): association between consumption
of scalding hot beverages and ESCC
Primary objectives
• 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
• To assess survival after ESCC diagnosis in Malawi
Secondary Objectives
• To identify and characterize common somatic genetic and epigenetic
alterations in ESCC tumors from Malawi
• To identify and characterize germline genetic and epigenetic
alterations associated with susceptibility to ESCC
Methodology
• Setting: Kamuzu Central Hospital; main referral hospital for central
Malawi and also a national teaching hospital
• In terms of cancer care, it is the only center available for north and
central Malawi serving a population of 8 million which is half of
Malawi’s population
• Population: All adults above 18 years of age undergoing endoscopy,
living within 50km of KCH and found to have a lesion that is suspected
or confirmed ESCC will be asked to enroll in the study
• Controls will be selected from the KCH in-patients at the dental,
orthopedic and eye departments matched by age, sex, ethnicity and
place of residence as closely as possible
• All those with confirmed ESCC or those with an endoscopic upper
esophageal pathology that is consistent with or likely to be ESCC will
be excluded from the control group
• Procedure: Participants or their legal guardian/independent witness
will be asked to sign an informed consent form
• Cases will have an esophageal tissue biopsy if unavailable
• Commercially available test kits will be used to test and determine
HIV prevalence in the samples. HIV RNA, CD4 and ART status will be
measured. H.Pylori will be tested using antigen test kits at the UNC
Project Lilongwe laboratory
• Urine samples will measure Poly Aromatic Hydrocarbons prevalence
using commercially available test kits
• The questionnaire used has been adapted from the one used in the
Thinker Study in Western Kenya
• Exposures; demographic characteristics, medical history, family
history of cancer, upper gastrointestinal symptoms, tobacco smoking,
alcohol use, consumption of hot drinks and beverages, maize storage,
H.Pylori presence and HIV presence/treatment
• Cases will be followed up at 3 month intervals for a period of 2 years
from enrollment by phone to assess vital status
• Sample size: 300 cases and 300 controls to examine our primary
exposures of interest (cumulative PAH exposure, beverage
temperature, diet, and HIV infection) over 3 years
• We anticipate prevalence of these exposures to range from 10% to
50% in our study, based on previous work in high-risk areas
• We are adequately powered (>80%) to detect odds ratios of 2.0
assuming 10%, 25% and 50% exposure prevalence at α=0.5 (SAS 9.4,
Cary North Carolina)
• Data analysis: Multiple conditional logistic regression will be used to
investigate the hypothesized associations among matched casecontrol pairs
• We will examine continuous PAH exposure, representing a cumulative
exposure from various sources assessed in the questionnaire and
from urine analysis. Beverage temperature, dietary factors, and HIV
infection will be analyzed categorically using conditional logistic
regression. Odds ratios and 95% confidence intervals will be
presented
• Survival estimates will be generated using Kaplan-Meyer curves to
estimate overall survival at 6, 12 and 24 months. All analyses will be
conducted in SAS 9.4 (Cary, North Carolina)
Current progress
• UNC contingent approval
• NHRSC awaiting review
Future plans
• East and Southern Africa ESCC consortium
• Community screening and intervention studies
References
1. Parkin D. M., Bray F., Ferlay J. & Pisani P.Global cancer statistics, 2002. CA
Cancer J Clin. 2005; 55, 74–108.
2. Munishi MO, Hanisch R, Mapunda O, Ndyetabura T, Ndaro A, Schüz J, Kibiki G,
McCormack V. Africa's oesophageal cancer corridor: Do hot beverages
contribute? Cancer Causes Control. 2015 Aug 6. [Epub ahead of print]
3. Yohannie M, Dzamalala C, Chisi J, Othieno-Abinya N. Oesophageal cancer and
Kaposi's Sarcoma in Malawi: a comparative analysis. Malawi Medical Journal.
2009;21(2):66–68.
4. Msyamboza KP, Dzamalala C, Mdokwe C, Kamiza S, Lemerani M, Dzowela T, et
al. Burden of cancer in Malawi; common types, incidence and trends: national
population-based cancer registry. BMC Res Notes. 2012;5:149.
5. Gopal S, Krysiak R, Liomba G. Building a pathology laboratory in Malawi. Lancet
Oncol. 2013;14(4):291–2. Cancer Med. 2015 Apr; 4(4): 588–595.
THANK YOU