Literature Reading

Distant Metastases of
Nasopharyngeal
Carcinoma
Yussy Afriani Dewi, Alfira Ulfa,
Nur Akbar Aroeman, Ongka M Saifuddin

DEPARTMENT OF OTORHINOLARYNGOLOGY-HEAD & NECK SURGERY

FACULTY OF MEDICINE PADJADJARAN UNIVERSITY-HASAN SADIKIN GENERAL HOSPITAL
BANDUNG
2021
 2

INTRODUCTION
 Nasopharyngeal Carcinoma
A squamous cell carcinoma arising from the
nasopharyngeal epithelium

Frequently found in the fossa of Rosenmuller

Johnson JT, Rosen CA. Bailey’s Head and Neck Surgery Otolaryngology vol 2. 2014. 3
 Nasopharyngeal Carcinoma
Most common 5-year survival rate:
4 th
cancer worldwide
45%
Affected by:
Incidence Age >40 years old

6.2/100,000 Advanced stage

Distant metastases

Indrasari S, Sudarman K, Fedriani J. The Primary Tumor and Regional Lymph Node Clinical Status of Distant Metastasis in Nasopharyngeal Carcinoma. J Otorhinolaryngol Hear
4
Balanc Med. 2018;1(2):9.
 China
13.4%
Distant
metastases
5-year survival rate:

22.3% Indonesia
12%

Myers JN, Hanna, Ehab YN, Myers EN. Cancer of the Head and Neck. 5th ed. Vol. 7, Wolters Kluwer. 2017.
Qu W, Li S, Zhang M, Qiao Q. Pattern and prognosis of distant metastases in nasopharyngeal carcinoma: A large-
population retrospective analysis. Cancer Med. 2020;9(17):6147–58. 5
Susilawati NK, Kadriyan H, Tengah KL. Bone Metastases in Nasopharyngeal Carcinoma. 2020;02(03):67–70.
Objective
To review NPC patients with
distant metastases

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 7

MATERIALS
AND METHODS
 Design Analytic case control study

Sampling Convenient sampling method

Materials &
Methods Hasan Sadikin General Hospital
Location and Santosa Hospital Kopo

Period January 2016 to December 2020

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 Subjects
Patients with distant Patients with distant
Case metastases of NPC Control metastases of NPC

Inclusion Criteria Exclusion Criteria

Patients with distant metastases of

nasopharyngeal carcinoma who came Incomplete data
during study period

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 Data Collected
General Characteristics Risk Factors

1. Age 4. Occupation
2. Gender 5. Chief Complaint
3. Education

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 Data Collected
General Characteristics Risk Factors

Consumption of:
• Alcohol
Smoking status
• Salted fish Exposure to:
• Instant noodle • Mosquito coils
• Canned food • Insecticide
• Soft drinks
• Grilled food
• Wood dust

11
 Categorical data

• Analyzed using Chi-square test or Exact

Fisher test
• Presented as frequency and percentage
Data
Analyzing Numerical data

• Analyzed using unpaired T test

• Presented as mean, median, standard
deviation and range

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 13

RESULTS
 554 patients with NPC
between 2016 to 2020

Study
45 patients with distant
metastases (8.1%)
Participants
3 patients were excluded

Case group Control group

42 patients with distant 42 patients w/o distant
metastases metastases

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 Characteristics N=84
Age  
<45 years old 28(33.3%)
45years old 56(66.7%)
Mean±Std 49.82±12.712
Median 50

General Range (min-max) 20.00-80.00

Characteristics
Gender  
Male 65(77.4%)

of Participants Female
Last education
19(22.6%)
 
Didn't attend school 2(2.4%)
Elementary school 22(26.2%)
Junior high school 15(17.9%)
Senior high school 37(44.0%)
Bachelor 8(9.5%) 15
 Characteristics N=84

Occupation  

Unemployed 5(6.0%)

Housewife 11(13.1%)

Entrepreneur 16(19.0%)

Employee 28(33.3%)

Labour 15(17.9%)

Health worker

Student
1(1.2%)

1(1.2%) General
Retired

Others
2(2.4%)
5(6.0%) Characteristics
Chief complaint

Malaise
 

5(6.0%)
of Participants
Neck lump 68(81.0%)

Bloody discharge 1(1.2%)

Epistaxis 1(1.2%)

Diplopia 1(1.2%)

Headache 4(4.8%)

Tinnitus 4(4.8%) 16
 Distant Metastases

Variable M0 M1 p-value

N=42 N=42

Age 0.643

<45 years old 15(35.7%) 13(31.0%)

45 years old 27(64.3%) 29(69.0%)

The Comparison of Mean±Std 49.17±12.927 50.48±12.615

Characteristics in Median

Range (min-max)
49.5

20.00-80.00
50

24.00-79.00

Patients With or Gender 0.434

Without Distant Male

Female
34(81.0%)

8(19.0%)
31(73.8%)

11(26.2%)

Metastases Last education 0.604

Didn't attend school 1(2.4%) 1(2.4%)

Elementary school 8(19.0%) 14(33.3%)

Junior high school 7(16.7%) 8(19.0%)

Senior high school 22(52.4%) 15(35.7%)

Bachelor 4(9.5%) 4(9.5%) 17

 Distant Metastases
Variable M0 M1 p-value
N=42 N=42
Occupation 0.785
Unemployed 1(2.4%) 4(9.5%)
Housewife 6(14.3%) 5(11.9%)
Entrepreneur 6(14.3%) 10(23.8%)
Employee 17(40.5%) 11(26.2%)
Labour
Health worker
8(19.0%)
1(2.4%)
7(16.7%)
0(0.0%) The Comparison of
Student 1(2.4%) 0(0.0%)
Characteristics in
Patients With or
Retired 0(0.0%) 2(4.8%)
Others 2(4.8%) 3(7.1%)
Chief complaint 0.991
Without Distant
Metastases
Malaise 2(4.8%) 3(7.1%)
Neck lump 34(81.0%) 34(81.0%)
Bloody discharge 0(0.0%) 1(2.4%)
Epistaxis 0(0.0%) 1(2.4%
Diplopia 1(2.4%) 0(0.0%)
Headache 1(2.4%) 3(7.1%)
Tinnitus 4(9.5%) 0(0.0%) 18
 Distant Metastases
Risk Factors M0 M1 p-value
N=42 N=42
Alcohol
Consumption 0.242
Yes 5(11.9%) 9(21.4%)
No 37(88.1%) 33(78.6%)  
Frequency 0.242
1-3x/week 5(11.9%) 9(21.4%)
None 37(88.1%) 33(78.6%)  
Amount 0.991
<1 glass/day 4(9.5%) 4(9.5%)

Risk Factors in
>1 glass/day 1(2.4%) 5(11.9%)
None 37(88.1%) 33(78.6%)  
Duration 0.991
Patients With NPC <12 months
>12 months
2(4.8%)
3(7.1%)
1(2.4%)
8(19.0%)
None 37(88.1%) 33(78.6%)  
Smoking
Smoking Status 0.306
Yes 30(71.4%) 34(81.0%)
No 12(28.6%) 8(19.0%)  
Amount 0.323
None 12(28.6%) 8(19.0%)
<12 cigarettes 12(28.6%) 8(19.0%)
12-24 cigarettes 13(31.0%) 21(50.0%)
>24 cigarettes 5(11.9%) 5(11.9%)   19
 Distant Metastases
Risk Factors M0 M1 p-value
N=42 N=42
Salted Fish
Consumption     0.175
Yes 31(73.8%) 36(85.7%)
No 11(26.2%) 6(14.3%)  
Age started 0.033*
<10 years old 10(23.8%) 22(52.4%)
10-18 years old 16(38.1%) 8(19.0%)
>18 years old 5(11.9%) 6(14.3%)
None
Mosquito Coils
11(26.2%) 6(14.3%)  
Risk Factors in
Usage
Yes
No
13(31.0%)
29(69.0%)
27(64.3%)
15(35.7%)
0.002*

 
Patients With NPC
Frequency 0.009*
<3/day 12(28.6%) 25(59.5%)
3-5/day 0(0.0%) 2(4.8%)
>5/day 1(2.4%) 0(0.0%)
None 29(69.0%) 15(35.7%)  

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 Distant Metastases
Risk Factors M0 M1 p-value
N=42 N=42
Wood dust 0.057
Yes 5(11.9%) 12(28.6%)
No 37(88.1%) 30(71.4%)  
Insecticide >1 year 0.265
Yes 2(4.8%) 6(14.3%)
No 40(95.2%) 36(85.7%)  
Instant Noodle 0.763
Yes 36(85.7%) 35(83.3%)
Risk Factors in No
Canned Food
6(14.3%) 7(16.7%)  
0.653

Patients With NPC Yes

No
27(64.3%)
15(35.7%)
25(59.5%)
17(40.5%)  
Soft Drink 0.801
Yes 32(76.2%) 31(73.8%)
No 10(23.8%) 11(26.2%)  
Grilled Food 0.321
Yes 29(69.0%) 33(78.6%)
No 13(31.0%) 9(21.4%)  
Family History 0.004*
Yes 4(9.5%) 15(35.7%)
No 38(90.5%) 27(64.3%)  
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 22

DISCUSSION
 General Characteristics
Most distant metastases were reported in male
• In line with another study conducted in
Yogyakarta and Palembang
• Higher exposure to carcinogenic materials
• Higher androgen levels
• VEGF-2578 expression
Indrasari S, Sudarman K, Fedriani J. The Primary Tumor and Regional Lymph Node Clinical Status of Distant Metastasis in Nasopharyngeal Carcinoma. J Otorhinolaryngol Hear Balanc Med. 2018;1(2):9.
Xiao G, Cao Y, QIu X, Wang We, Wang W. Influence of gender and age on the survival of patients with nasopharyngeal carcinoma. Int J Cancer. 2013;43(4):685– 91. 23
Utama DS. The Characteristics of Nasopharyngeal Carcinoma Patients in Moehammad Hoesin General Hospital Palembang January 2013 - December 2017. Int J Nasopharyngeal Carcinoma. 2019;1(1):30–2.
 General Characteristics
Mostly seen in older population
• NPC is a chronic condition
• Indrasari et al.: peak age of distant metastases in NPC occurs in the
40-50 years old group
Majority had 9-12 years of formal education
• The low education  reduced access to information about
diagnosis and treatment
• Influences their lifestyle
Indrasari S, Sudarman K, Fedriani J. The Primary Tumor and Regional Lymph Node Clinical Status of Distant Metastasis in Nasopharyngeal Carcinoma. J Otorhinolaryngol Hear Balanc Med. 2018;1(2):9.
McDonald JT, Johnson-Obaseki S, Hwang E, Connell C, Corsten M. The relationship between survival and socio-economic status for head and neck cancer in Canada. J Otolaryngol - Head Neck Surg. 2014;43(JAN):2–7. 24
Dantas TS, De Barros Silva PG, Sousa EF, Da Cunha MDP, De Aguiar ASW, Costa FWG, et al. Influence of educational level, stage, and histological type on survival of oral cancer in a brazilian population: A retrospective study of 10 years observation. Med (United States). 2016;95(3):1–10.
 Risk Factors
In this study:
The most risk factors reported are consumption
of salted fish (85.7%), instant noodle (83.3%) and
smoking history (81.0%)

The least risk factors reported were wood dust

(28.6%) and insecticide exposure (14.3%)
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 Risk Factors
Salted fish and preserved goods consumption
• A well-known risk factors of NPC especially in endemic areas
• Contain N-nitrosamines, a carcinogenic substance

Family history
• Genetic susceptibility in nitrosamine metabolism
• Cytochrome P450 mutation and Human Leukocyte Antigen (HLA) haplotype
associated with NPC such as HLAA1, AW19, BW46 and B17
• Statistically difference between patients with and without family history of NPC as
seen in this study

Utama DS. The Characteristics of Nasopharyngeal Carcinoma Patients in Moehammad Hoesin General Hospital Palembang January 2013 - December 2017. Int J Nasopharyngeal Carcinoma. 2019;1(1):30–2.
Handayani R, Afriani Dewi Y, Madani DZ. Prevalence of Nasopharyngeal Carcinoma Patients in Departement of Orl-Hns Hasan Sadikin General Hospital 2010 -2017. Int J Nasopharyngeal Carcinoma. 2020;2(01):01–3. 26
Hardianti RA, Dewi YA, Utami RD. Risk Factor of Nasopharyngeal Carcinoma Dr. Hasan Sadikin General Hospital Bandung. Int J Nasopharyngeal Carcinoma. 2019;1(03):110–1.
 Risk Factors
Tobacco smoking
• ↑ the risk of developing NPC by 5.8 times higher than non-smokers population
• The risk of NPC increases parallel to the number of tobaccos smoked
• Act as mutagen which results in DNA damage and tumorigenesis

Alcohol consumption
• Drinking >7 drinks a week is an independent risk factor of NPC
• Acetaldehyde  local carcinogen interfering with the repair site of genes and the
synthesis of genes
• ↑ the activity of mucosal cytochrome P450 enzyme  formation of free radicals and
cell damage

Zou L, Zhong R, Shen N, Chen W, Zhu B, Ke J, et al. Non-linear dose-response relationship between cigarette smoking and pancreatic cancer risk: Evidence from a meta-analysis of 42 observational studies. Eur J Cancer. 2014;50(1):193–203.
Long M, Fu Z, Li P, Nie Z. Cigarette smoking and the risk of nasopharyngeal carcinoma: A meta-analysis of epidemiological studies. BMJ Open. 2017;7(10):14– 7. 27
Du T, Chen K, Zheng S, Bao M, Huang Y, Wu K. Association Between Alcohol Consumption and Risk of Nasopharyngeal Carcinoma: A Comprehensive Meta- Analysis of Epidemiological Studies. Alcohol Clin Exp Res. 2019;43(11):2262–73.
 Risk Factors
Wood dust exposure
• Associated with occupational risk  doesn’t frequently occur in our
participants
• May accumulates and causes irritation and inflammation

Insecticide exposure
• A study conducted in Nigeria showed the genotoxicity effects of
agricultural chemical  containing nitrates

Susilawati NK, Kadriyan H, Tengah KL. Bone Metastases in Nasopharyngeal Carcinoma. 2020;02(03):67–70.
Adoga AA, Kokong DD, Nimkur TL, Ma’an ND. Environmental and Life-Style Related Risk Factors for Sinonasal and Nasopharyngeal Malignancies among a Prospective Cohort in Jos, Nigeria. Int J Otolaryngol. 2018;2018:1–6. 28
 Risk Factors
Grilled food
• During grilling process, heterocyclic amines or polycyclic aromatic hydrocarbons can
be formed
• Linked to the cell damage and disruption leading to mutation and carcinogenesis

Mosquito coils
• Most common risk factor of NPC in Indonesia and Malaysia
• In this study, mosquito coils showed a significant difference between the user and
non-user and also the frequency per day
• Contain formaldehyde and acetaldehyde

Hardianti RA, Dewi YA, Utami RD. Risk Factor of Nasopharyngeal Carcinoma Dr. Hasan Sadikin General Hospital Bandung. Int J Nasopharyngeal Carcinoma. 2019;1(03):110–1.
Sharma TD, Singh TT, Laishram RS, Sharma LDC, Sunita AK, Imchen LT. Nasopharyngeal carcinoma--a clinico-pathological study in a regional cancer centre of northeastern India. Asian Pac J Cancer Prev. 2011;12(6):1583–7. 29
Septiani W, Dewi YA, Afriandi I. Association between Mosquito Coils Use with Nasopharyngeal Carcinoma. 2020;02(03):79–81.
 Study Limitation
Small number of the participants

Doesn’t include the odds ratio of each variable

Further analysis can be designed to associate each variable to the risk

of NPC with distant metastases

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CONCLUSION
 32

CONCLUSION
The initiation age of salted fish consumption, usage
of mosquito coils and family history are
significantly associated with distant metastases of
nasopharyngeal carcinoma

Special attention should be given to these

populations to decrease the incidence of
distant metastases and improve the outcome
THANK YOU

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