Journal Reading

Occupational Exposures and Risk of

Nasopharyngeal Carcinoma in a High-Risk
Area: A Population-Based Case-Control Study

Presentant: dr. Revy Octarian Palmendha

Supervisor: : Dr. dr. Yussy Afriani Dewi, Sp.T.H.T.B.K.L, Subsp. Onk(K)., FICS

DEPARTMENT OF OTORHINOLARYNGOLOGY-HEAD & NECK SURGERY

FACULTY OF MEDICINE PADJADJARAN UNIVERSITY-HASAN SADIKIN GENERAL HOSPITAL
BANDUNG
2023
 INTRODUCTION

Malignancy with a distinctive geographic and

NPC ethnic distribution worldwide

2018 :
>129,000 new cases of NPC
>52,000 cases occurred in southern China
• nonkeratinizing undifferentiated carcinomas
Type • keratinizing undifferentiated carcinomas
• keratinizing squamous cell carcinoma
 Introduction
Dramatic
difference in the
Infection with incidence among
EpsteinBarr virus populations and Occupational
(EBV) is considered geographic areas exposure as a
the most strongly suggests potential NPC risk
prominent risk the involvement of factor  still
factor for NPC genetic and poorly understood
development environmental
factors in NPC
development.
 MATERIALS AND METHODS

Study Population • Multicenter collaborative study

• 2010-2014
• Participants were individuals aged 20 to 74 years residing in the study
area
• No history of malignant disease or congenital or acquired
immunodeficiency.

3047 patients who had histopathologically confirmed 3202 potential controls

2648 (83%) consented to participate

2554 (84%) agreed to participate (cases).
(controls).
 FINAL SAMPLE

2514 cases 2586 controls

 Data Collection
Face-to-face or telephone
interviews
• implemented by trained interviewers
using a structured electronic
questionnaire
Collected information
• demographics
• body size
• residential and occupational history
• history of chronic ear, nose, and
respiratory tract conditions
• family history of NPC and other cancers
• cigarette smoking
• alcohol consumptio
• tea consumption; dietary habits; and use
of Chinese herbal medicine
Occupational history

Assessed  the ages at which individuals started and ended full-time work
(>20 hours per week) and all occupations held for ≥1 year

Listed from the earliest to the most recent job, including housework.

Exposure to any type of occupational dusts, chemical vapors,

exhausts/smokes, acids, or alkalis on the job
 Statistical Analyses

Compared the distribution of demographics and other potential

confounders between NPC cases and controls using χ2 tests

Multivariate logistic regression  to estimate Ors and

corresponding 95% CIs for associations between the risk of NPC
and occupational exposures.
 Statistical Analyses

occupational
current housing
exposure, ie, cottage [clay brick
age, sex, and type (building
educational level structure], or
geographic area [concrete
(≤6, 7-9, 10-12, or boat)
structure]
>12 years)

first-degree family
history of NPC cigarette smoking
EBV seropositivity
(yes, no, or (ever or never).
unknown)
 Duration of occupational exposure

obtained for each participant by totaling the exposure time from each
occupation.

Used restricted cubic splines to characterize relations between NPC

risk and duration of occupational exposure

Using the Wald χ2 test

 To evaluate potential effect
modification by sex, age
group, education level, current
Likelihood ratio tests
housing type, first-degree
family history of NPC, and
cigarette smoking.
 Sensitivity Analyses

recalculation of the duration of exposure excluding

exposures that occurred in the 5 years preceding
diagnosis/interview (5-year lag)

restricted to individuals aged 30 to 60 years who

are the majority of the workforce (4118 of 5100
individuals

restricted to EBV VCA-IgA–seropositive individuals

 Statistical Test

occupational exposure
large numbers of history assessed
statistical tests retrospectively 
misclassification bias.

calculated P values using Sensitivity and

the false discovery rate Additional sensitivity specificity among cases
method to correct for analysis and controls using the
multiple comparisons. SAS macro %sensmac
 RESULT
Demographics of the Study Population

• Cases were slightly younger than controls Cases

less educated, live in a cottage or boat
• first-degree family history of NPC
• have positive IgA antibodies against the EBV
viral capsid antigen.
Broad Categories of Occupational Exposures

Among individuals who were exposed to occupational dust (n = 3644)

61.4% reported exposure to soil dust

Among those who were exposed to occupational chemical vapors (n = 2911)

76.2% reported exposure to pesticides.

No association between occupational exposure to soil dust or pesticides and the

risk of NPC
Broad Categories of Occupational Exposures

Positive association between exposure to chemical vapors (excluding pesticides) in

the workplace and NPC risk

Linear duration-response relation between occupational dusts or chemical vapors

and NPC risk (dusts: P for nonlinearity = .107; chemical vapors: P for nonlinearity
= .269)

the relations were not pronouncedly linear

Slightly stronger associations of
exposure to occupational dusts or
chemical vapors with NPC risk were
observed  EBV antibody status
Subtypes of Occupational Exposures

Individuals who were no association was

exposed to dust from observed with
metals, textiles, exposure to wood
cement, or coal were dust, leather dust, or
at 30% to 61% excess chalk dust
risk of NPC compared
with those who were
unexposed
Subtypes of Occupational Exposures

The risk of NPC was No association was

nearly doubled (95% observed with
CI, 1.53- 2.45) for occupational exposure
those who were to vapors from wood
exposed to preservatives or paint.
other/unspecified
dusts (asbestos dust,
incense dust)
 Subtypes of Occupational Exposures

Occupational exposure to industrial acids (including sulfuric acid,

hydrochloride, and nitric acid) or alkalis (including concentrated
alkali and ammonia) was associated with a 1.6-fold increased risk of
NPC

Most of the evaluated subtypes of occupational exposures

exhibited positive trends between the risk of NPC and increasing
duration of exposure or younger age at first exposure
 Joint Association and Effect Modification

• The subtypes of occupational exposures were selected and combined

based on the potential for coexposure in the workplace

• Compared with individuals who did not report exposure to any of the
occupational agents assessed

• Who reported occupational exposure to dust from textiles or leather, but

not to organic solvents, had an OR of 1.70 (95% CI, 1.24-2.33)

• The OR for occupational exposure to organic solvents, without exposure

to textile/leather dust,
 Sensitivity Analyses

• Excluded exposures during the 5 years preceding diagnosis/interview (5-

year lag)  OR estimates were similar to those from the primary
analysis without a lag

• Restricting the analysis to individuals aged 30 to 60 years nor limiting the

analysis to individuals who were seropositive for EBV VCA-IgA 
materially different findings
 DISCUSSION

population-based Exposures to broad categories of occupational dusts,

study in China chemical vapors, exhausts/smokes, and acids/alkalis
were associated with an increased risk of NPC.

Driven by 14 subtypes of occupational agents within the 4 categories.

even earlier case-control studies

• 2 studies detected a significant positive association with occupational

exposure to dusts
• 4 studies reported an increased risk of NPC with occupational exposure to
exhausts/smokes
• 3 studies observed elevated risks for occupational exposure to
chemicals/chemical fumes.

strictly population-based case-control study, after controlling for

This Study numerous potential confounders, we observed a significant
increase in the risk of NPC in relation to occupational exposure
Subtypes of occupational agents

• the positive associations were primarily driven by dusts from

metals, textiles, cement, or coal; vapors from formaldehyde,
organic solvents, or dyes; exhausts or smokes of diesel, firewood,
asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric
acid, nitric acid, concentrated alkali, and ammonia
 the International Agency for Research on Cancer concluded in 2006
sufficient evidence from epidemiologic studies supports the carcinogenicity
of formaldehyde in NPC

recent research
that the relations between occupational formaldehyde exposure and NPC
remains inconclusive.

positive link between occupational exposure to formaldehyde and NPC, we

This Study did not observe a positive duration-response trend, and we lacked
information on exposure intensity or cumulative exposure.
 Malaysia and Hong Kong
no association of NPC with occupational exposure
to dust from metals, construction/ silica, textiles,
or coal

increased risks of NPC associated with these

This Study exposures along with positive duration-response
relations.
 case-control study in southern China
positive duration response relation between the risk of
NPC and exposure to occupational combustion
products, especially from welding, coal/coke, liquid
fuels, and other materials.

occupational exposure to smoke or exhaust from diesel,

This Study firewood, asphalt/tar, vehicle, and welding was associated
with an elevated risk of NPC, with positive duration-
response trends.
 Strengths of this study

• Large sample size, the population-based setting

• The enrollment of individuals with incident
• Histopathologically confirmed NPC
• The random selection of controls from the study base
• High participation rates in cases and controls, and
detailed information on numerous potential
confounders.
 Limitations

• occupational exposure was assessed based on self-report, with no

validation of reported data  Recall bias and misclassification
• many of the subtypes of occupational exposuresthat we assessed
remained nonspecific
• lacked information on the intensity and probability of occupational
exposure
• Did not have information regarding the use of personal protective
equipment or other exposure control measures used in the
workplace.
 CONCLUSSION
• By using a large-scale, population based study
with adequate controlling for confounders, we
have provided new evidence supporting an
etiologic role of several occupational
exposures in NPC development in a high-
incidence region
THANK
YOU
CRITICAL APPRAISAL JOURNAL
(external Validity)

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 How big is the effect size of the output?

in this study, Exposures to broad categories of occupational dusts, chemical vapors,

exhausts/smokes, and acids/alkalis were associated with an increased risk of NPC.

The effect size of this study was calculated used the calculation with Multivariate
logistic regression
The result of this study showed statistically significant difference and provided new
evidence supporting an etiologic role of several occupational exposures in NPC
development
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 How accurate is the estimate of the effect of the outcome?

Since the effect size in this study was calculated, this study
concluded accurate.

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 Can you trust the results of this study?

The study has large sample and the methods used in this research were sufficiently correct. The results can
be trusted because it has considered factors that may affect the primary or secondary outcome.

42
 Can the study results be applied to the local population?

This research methodology is valid. The results of this study can already be applied to the local population
because the patient characteristics and exposure to cancer in Indonesia are the same as the study.

43
Are the results of this study compatible with other available studies?

It was stated in this study that the findings were the same as previous studies. For example, in several
studies such as the International Agency for Research on Cancer concluded in 2006 obtaining sufficient
evidence from epidemiologic studies supporting the carcinogenicity of formaldehyde in NPC, in this study
the results obtained a positive link between occupational exposure to formaldehyde and NPC, we did not
observe a positive duration-response trend, and we lacked information on exposure intensity or
cumulative exposure.

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GRADE OF RECOMMENDATION

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