Vaccine 26S (2008) M71M79

Contents lists available at ScienceDirect

Vaccine
journal homepage: www.elsevier.com/locate/vaccine

ICO Monograph Series on HPV and Cervical Cancer: Asia Pacic Regional Report

Epidemiology and Prevention of Cervical Cancer in Indonesia, Malaysia,

the Philippines, Thailand and Vietnam
Efren J. Domingo a, , Rini Noviani b , Mohd Rushdan Md Noor c , Corazon A. Ngelangel d ,
Khunying K. Limpaphayom e , Tran Van Thuan f , Karly S. Louie f , Michael A. Quinn g
a

Department of Obstetrics and Gynecology, University of the Philippines College of Medicine - Philippine General Hospital, Manila, the Philippines
Sub-Directorate of Cancer Control, Directorate of Non Communicable Disease Control, Directorate General of Disease Control and Environmental Health and
Ministry of Health of the Republic of Indonesia, Jakarta, Indonesia
c
Gynaecology Oncology Unit, Department of Obstetrics and Gynaecology, Hospital Sultanah Bahiyah, Alor Star, Kedah, Malaysia
d
Clinical Epidemiology Unit, Department of Medicine, Philippine General Hospital, University of the Philippines, Manila, the Philippines
e
Department of Obstetrics and Gynaecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
f
Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Program (CERP), Institut Catal dOncologia - Catalan Institute of Oncology (ICO),
LHospitalet de Llobregat (Barcelona), Spain
g
Oncology and Dysplasia Unit, Royal Womens Hospital, Melbourne, Victoria, Australia
b

a r t i c l e
Keywords:
Asia Pacic
Indonesia
Malaysia
Philippines
Thailand
Vietnam
HPV
Cervical cancer
Prevalence
Vaccine

i n f o

a b s t r a c t
Cervical cancer remains one of the leading causes of cancers in women from Indonesia, Malaysia, the
Philippines, Thailand and Vietnam. High-risk human papillomavirus (HPV) types, particularly HPV-16 and
18, are consistently identied in cervical cancer cases regardless of geographical region. Factors that have
been identied to increase the likelihood of HPV exposure or subsequent development of cervical cancer
include young age at rst intercourse, high parity and multiple sexual partners. Cervical cancer screening
programs in these countries include Pap smears, single visit approach utilizing visual inspection with
acetic acid followed by cryotherapy, as well as screening with colposcopy. Uptake of screening remains
low in all regions and is further compounded by the lack of basic knowledge women have regarding
screening as an opporunity for the prevention of cervical cancer. Prophylactic HPV vaccination with the
quadrivalent vaccine has already been approved for use in Malaysia, the Philippines and Thailand, while
the bivalent vaccine has also been approved in the Philippines. However, there has been no national or
government vaccination policy implemented in any of these countries.
2008 Elsevier Ltd. All rights reserved.

1. Introduction

2. Burden of cervical cancer in Southeast Asia

The burden of cervical cancer in Southeast Asia is moderately

high, where the costs of nationwide organized cytology screening have been a signicant limitation. The use of Pap testing for
cytology-based screening has been highly effective in preventing
cervical cancer in industrialized countries and will most likely be
effective in countries where screening is limited or nonexistent.
Hence, the use of alternative screening modalities, such as visual
inspection of the cervix aided by acetic acid (VIA) with or without
magnication, is currently under evaluation. In addition, prophylactic human papillomavirus (HPV) vaccination for the prevention
of infection and related disease is being considered as an additional
cervical cancer control strategy.

2.1. Cervical cancer incidence and mortality

Tel.: +63 2 5255908; fax: +63 2 5255908.

E-mail address: efrendomingo@hotmail.com (E.J. Domingo).
0264-410X/$ see front matter 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.vaccine.2008.05.039

Cervical cancer is the leading cancer in women in Vietnam and

Thailand, and the second most common cancer in Malaysia, the
Philippines and Indonesia [1]. Furthermore, it is the most common
cause of death in women in Vietnam, the second in Indonesia and
the Philippines, third in Thailand and fourth in Malaysia [1].
In Southeast Asia, cervical cancer incidence (age-standardized
rate (ASR) 15.7 per 100,000) is similar for Indonesia and Malaysia.
Higher and similar ASRs are observed between the Philippines
(ASR: 20.9), Thailand (ASR: 19.8) and Vietnam (ASR: 20.2) [1].
Fig. 1 shows the ASR of cervical cancer in countries with existing cancer registries and the high variability within Malaysia, the
Philippines and Thailand [2]. An ASR of 17.5 was reported in the
Rizal province of the Philippines (19931997) [3]; this rate does
not differ signicantly from recent unpublished data nor from that
of Manila (ASR: 19.8). In Vietnam, the incidence is intermediate,

M72

E.J. Domingo et al. / Vaccine 26S (2008) M71M79

in Chiang Mai and 54.5% in Khon Kaen. The annual cost of care is
estimated at US$10 million [9].
2.1.5. Vietnam
There are over 29 million women in Vietnam over the age of
15 years. More than 6,000 new cases of cervical cancer and 3,000
deaths are estimated each year. Cervical cancer ranks as the second
most common cancer in women ages 1544 years [4].
3. HPV prevalence in Southeast Asia
3.1. HPV prevalence in cervical cancer: Indonesia, Malaysia, the
Philippines and Thailand

Figure 1. Age-standardized (world) incidence rates of cervical cancer by cancer

registries (19982002) in Malaysia, the Philippines, and Thailand [2].

however rates were 4-fold higher in Ho Chi Minh City in the south
compared to Hanoi in the north [3].
2.1.1. Indonesia
Each year approximately 15,000 new cervical cancer cases and
7,500 cancer-related deaths are reported. It is the second most frequent cancer in women of reproductive age 1544 years [4].
2.1.2. Malaysia
In Malaysia, the overall incidence rate is 19.7 per 100,000
women, however differs by ethnic group. Ethnic Chinese women
have the highest ASR of 28.8 per 100,000, followed by ethnic Indians with 22.4 and ethnic Malays (includes Peninsular Malaysia but
not East Malaysia) with 10.5 per 100,000 women [5].
2.1.3. The Philippines
According to the Filipino cancer registry 2005 annual report, the
incidence of cervical cancer remained stable from 1980 to 2005 [6].
The overall 5-year survival rate was 44% and mortality rate was 1 per
10,000 women. The high mortality rate is attributed to the fact that
75% of women are diagnosed at late stage disease with treatment
being frequently unavailable, inaccessible or non-affordable.
The Philippines General Hospital (PGH) has been the countrys
government tertiary center reporting the highest number of new
cervical cancer cases. In 2006, 466 new cases were reported, of
which 68% were squamous cell carcinoma, 21% adenocarcinoma,
3% adenosquamous and 8% of other histology. More than 70% of
cases presented at stage IIB disease or greater, with 4045% in
stage IIIB. Treatment-related costs for patients with cervical cancer exceeded twice the average annual income in the Philippines
with an average cost of US$3501,100 for diagnosis and pretreatment evaluation, US$1,1004,850 for surgery and US$2,1006,000
for chemoradiation) [7].
2.1.4. Thailand
In 2002, 6,243 new cervical cancer cases and 2,620 cancerrelated deaths were reported [1]. Incidence of cervical cancer from
1990 to 2000 remained constant. Squamous cell carcinoma is the
most common histopathological type accounting for 8086%, followed by adenocarcinoma/adenosquamous carcinoma accounting
for 1219% [8]. The age of women diagnosed with cervical cancer
presented as early as 20 years and peaked in women 4550 years.
Most cases are diagnosed in advanced stages of disease with 51% in
International Federation of Gynecology and Obstetrics (FIGO) stage
II and 31% in stage III. The overall 5-year survival rates are 68.2%

Fig. 2 shows the ve most frequent HPV types in cervical cancer

in Indonesia, Malaysia, the Philippines and Thailand [10,11]. No data
are available for Vietnam. HPV-16 and 18 are the two most common
HPV types in Southeast Asia, although HPV-18 alone is relatively
more frequent compared to the type distribution estimates in the
rest of the world. This is noteworthy for Indonesia where it is the
leading HPV type in cervical cancer (52 cases of 121). It is unclear
why HPV-18 has such a high prevalence in this population [12]. The
estimate for Malaysia is based on a small number of cases (N = 23)
and there was a high number of co-infections for HPV-16 and 18,
therefore, the interpretation of these data is limited.
3.2. HPV prevalence in women with normal cytology: Indonesia,
the Philippines, Thailand and Vietnam
There is a wide variation of the ve most frequent high-risk HPV
types in women with normal cytology in Southeast Asia (Fig. 3). No
data are available for Malaysia. HPV-16 remains the most frequent
type in Thailand and Vietnam, and the second most frequent type
for Indonesia and the Philippines. Although the HPV type distribution in cervical cancer for Vietnam is unknown, HPV-18 ranks
as the fourth most frequent type in women with normal cytology.
In Indonesia, HPV-51 is the most common HPV type although not
identied as one of the ve most prevalent types in cervical cancer
cases, implying its less relative importance for disease. HPV-18 is
the most frequent type in cervical cancer cases but it is not highly
prevalent in women with normal cytology in Indonesia [1113].
4. Risk factors for HPV infection and cervical cancer
The prevalence of cofactors - smoking, oral contraceptive use,
and fertility - for cervical carcinogenesis in Southeast Asia are
shown in Table 1.
4.1. Indonesia
Similar to other countries, factors that increase the risk of
cervical cancer include young age at rst intercourse, multiple
sexual partners and high parity. A cervical cancer case-control
study among women in Jakarta reported that women having more
than one sexual partner (OR: 5.83; 95% condence interval (CI):
2.9811.36) and high parity (>3) (OR: 2.7; 95%; CI: 1.554.72) were
at an increased risk for cervical cancer and women with an older age
(20 years) at rst sexual intercourse (OR = 0.48; 95% CI: 0.280.85)
were at a decreased risk [12].
4.2. Malaysia
In a cross-sectional school survey of 1219 year old adolescents,
5.4% (of which 8.3% were males and 2.9% were females) reported

E.J. Domingo et al. / Vaccine 26S (2008) M71M79

M73

Figure 2. Five most frequent HPV types in women with cervical cancer in Indonesia, Malaysia, the Philippines, and Thailand [10,11].

Figure 3. High-risk HPV prevalence in women with normal cytology in Indonesia, the Philippines, Thailand, and Vietnam [13].

Table 1
Prevalence of smoking, oral contraceptive use, and total fertility in Malaysia, the Philippines, and Vietnam
Cofactors

Indonesia
Malaysia
The Philippines
Vietnam
Sources of data: [4,28,31].

Current smoking (% of women)

Ever use of oral contraceptives (%)

Total fertility Rate (per woman)

2.9
11.6
8.1
8.0

13.2
13.4
13.2
6.3

2.8
2.8
3.0
2.2

M74

E.J. Domingo et al. / Vaccine 26S (2008) M71M79

having had sexual intercourse [14]. Median age at rst sexual intercourse was 15 years; however, this estimate may be underreported
given that talking about sex is a culturally taboo subject in Malaysia.
However, an increasing proportion of adolescents are engaging in
premarital sex, which may reect the rapid social changes in the
country and the increased likelihood of being exposed to HPV and
other sexually transmitted infections (STI).
4.3. The Philippines
A case-control study in the Philippines reported that women
with less household amenities (a proxy for socioeconomic status),
having ever smoked, and having given birth six or more times were
at an increased risk of squamous cell carcinoma [15]. There was a
lower risk of cervical cancer with decreasing time interval from the
last Pap smear.
4.3.1. Adolescent and young adult sexual health prole
The 2005 World Health Organization-Western Pacic Regional
Ofce (WHO-WPRO) reported the mean age of sexual debut to be
1415 years [16]. In 2002, 23% of young adults had engaged in premarital sex and the number has steadily increased over the last
decade. Moreover, about 10% of young women reported that their
rst premarital sex experience was without their consent [16].
Premarital sex initiates and/or accelerates entry into marriage and the Filipino youth marry at an early age. An estimated
1.6 million young adults aged 1527 years, or 34% of the countrys
youth, have had multiple sexual partners.
The prevalence of STIs such as gonorrhea and Chlamydia trachomatis is high among young people. Human immunodeciency
virus (HIV) infection in females occurs at a younger age group compared to males (47% of infected females are between 2029 years).
Risky sexual behavior is common among the youth. Only 26%
of sexually active adolescents admitted to having used contraceptives, with condom use as the most common method. Of the 78%
male adolescents who do not use contraceptives, 6% engage in
commercial sex. Similarly, there is an increasing number of female
adolescents engaging in unprotected commercial sex (17% in 1994
and 30% in 2002).
Among sexually active adolescents, knowledge on contraception
is poor, increasing their risk of exposure to HPV. Of those surveyed,
27% thought that the pill must be taken just prior to or straight
after sexual intercourse. Only 4% of young women can be considered knowledgeable on the subject of contraceptives and family
planning.
4.4. Thailand
Case-control studies have identied increasing number of lifetime sexual partners, having one or more STIs, smoking, high parity,
oral contraceptive use and decreasing age at rst sexual intercourse
as risk factors for cervical squamous cell carcinoma (SCC) [1719].
Furthermore, in a case-control study among monogamous women

with cervical cancer, women whose husbands rst visited commercial sex workers at 19 years of age or younger and rarely or never
used condoms were at an increased risk of SCC (OR: 2.67; 95%;
CI: 1.365.23) compared to women whose husbands never visited
commercial sex workers.
There is some evidence that diet and nutrition may inuence
cervical cancer. In a study conducted in Bangkok, high intake of
foods rich in Vitamin A, particularly in high-retinol foods, may
reduce the risk of carcinoma in situ, suggesting inhibition of the
progression to invasion [20].
In a population-based study of predominantly monogamous
women (85%), HPV positivity was associated with herpes simplex virus type 2 (HSV-2) seropositivity (OR: 1.9; 95% CI: 1.22.8),
and extramarital affairs of the womans husband (OR: 1.5; 95% CI:
1.022.3). Also, HPV positivity was highest among women <25 years
of age, consistent with the increased risk of HPV infection at early
age at rst sexual intercourse [21].
4.4.1. Adolescent and young adult sexual health prole
Similar to western societies, Thai adolescents have become more
sexually active, but they are not practicing safe sex, which has led to
an increased risk of spreading STIs more rapidly [22,23]. The high
HPV prevalence in this population may be partially explained by
the transmission of STIs, often asymptomatic and under-diagnosed,
which can be associated with having multiple sexual partners. Findings from several surveys are summarized in Table 2. These results
show that the median age of sexual debut reported among adolescents age 1325 years was 16 years for males and 18 years for
females.
4.5. Vietnam
Two population-based surveys were conducted among married
women aged 1569 years in Ho Chi Minh City and Hanoi [24]. HPV
prevalence was 5-fold higher in Ho Chi Minh City (10.9%) than in
Hanoi (2.0%) with a peak prevalence observed in women younger
than 25 years in Ho Chi Minh City and not Hanoi. The differences in
prevalence cannot be readily explained. However underreporting
of lifetime number of sexual partners and geographical isolation of
the north compared to the south during past decades of war could
offer a partial explanation.
Also, being nulliparous was associated with an increase risk of
HPV DNA positivity. HSV-2 seropositivity and current oral contraceptive use was associated with HPV infection in Ho Chi Minh City
but not Hanoi.
4.5.1. Adolescent and young adult sexual health prole
Recent social and economic changes in Vietnam, such as the
development of factories and other industries, have increased
the opportunity and openness for premarital sex among youths
[25]. Even though premarital sex is more common, many practice unsafe sex as condom use was perceived negatively because
it decreases pleasure and is only appropriate for prostitutes and

Table 2
Outcomes from sexual behavior surveys in Thailand

Age range surveyed

Ever had sexual intercourse
Median age at sexual debut
a
b

Source data: [22].

Source data: [23].

Secondary schoola

Students and factory

workersb

Unmarried factory
workersb

Rural North and Northeast

Thailandb

1315 years
19.1% males
4.7% females

1519 years

3% females
18 years

1325 years
75% males
6% females
16 years males
18 years females

51% males
2% females
16 years males
18 years females

E.J. Domingo et al. / Vaccine 26S (2008) M71M79

Table 3
Outcomes from sexual behavior surveys in Vietnam

Age range
Sexually active
Used condoms (rst intercourse)
Multiple sex partners
Sex with high risk partner (drug
user or commercial sex worker)
Median age at sexual debut
a
b

General populationa

College studentb

1829 years
50% males and
females
32.8% males
10.8% females
56.7% males
9.2% females
27% males

1724 years
15% males 2% females

5% females
21.3 years males
22.7 years females

20 years

Source of data: [25].

Source of data: [23].

people engaging in extramarital affairs [25]. These data clearly suggest an increase in risk and spread of HPV and other STIs. Table 3
summarizes the results from sexual behavior surveys that report
a higher frequency of multiple partners and sexual activity with
high-risk partners.
5. Current cervical cancer screening programs
5.1. Indonesia
As part of the Female Cancer Program: See & Treat Project in
Indonesia, where women are seen, diagnosed and treated during
their single visit to the clinic, 13,923 women were screened from
October 2004 to May 2005 in Jakarta, Taskimalaya and Bali [26].
The aim of the program was to screen and treat in a one-visit setting
with visual inspection with acetic acid (VIA) and immediate treatment with cryotherapy was offered for those with pre-malignant
cervical disease. The study focused on women aged 2555 years of
low socioeconomic status in rural areas. This program has successfully screened more than 50% of women with an income less than
US$3 per day, 3360% of women with only limited primary education, and about 8095% of women who had never been screened
before.
A pilot cervical cancer screening program using a single visit
approach (VIA and cryosurgery) in women aged 2549 years was
started in 2006 and is currently ongoing in six provinces: Deli Serdang (North Sumatera Province), Gowa (South Sulawesi Province),
Karawang (West Java Province), Gunung Kidul (DI Yogyakarta
Province), Kebumen (Central Java Province) and Gresik (East Java
Province). Tests are performed by doctors and midwives in community health centers with technical supervision by gynecologists and
management supervision by District and Provincial Health Ofcers
[27].
5.2. Malaysia
The cervical cancer screening program was started in 1969 using
the conventional Pap smear. Screening was later extended in 1981
to include all family planning users. In 1995 various agencies, such
as the National Population and Family Development Board (NPFDB),
private clinics and hospitals, university and army hospitals, and
non-governmental organizations like the Federation of Family Planning Association of Malaysia (FFPAM) provided Pap smear services
as part of a cancer campaign where the Pap testing was available
once every 3 years for all females aged 2065 years.
According to the World Health Organization (WHO) Health Surveys 2001/2002, Pap smear coverage was only 23%. The highest Pap
smear uptake was among women aged 3039 years (36.6%) compared to women in other age groups: 1829 years (14.6%), 4049

M75

years (28.8%), 5059 years (20.9%) and 6069 years (5%) [28]. The
most recent 2003 National Guidelines on Pap Smear Screening recommended that all sexually active women aged 2065 years should
attend screening annually for two consecutive years [29]. If both
smears are normal, screening can continue every 3 years. In that
same year, the Malaysian Ministry of Health allocated 3.55 million
Malaysian ringgit for free Pap smear tests to women attending
public health facilities. The predominant screening method is conventional cytology with only a few public health services and the
private sector offering liquid-based cytology.
In 2005, public health facilities and government hospitals contributed 69% of all Pap smear tests compared to private health
facilities, which contributed only 20.6%. From 1996 to 2005, the
annual number of Pap tests ranged from 350,000 to 400,000
smears, with no signicant variation in the total number of tests
over the years.
Abnormal Pap smears and unsatisfactory ones for evaluation
accounted for 0.86% and 3.1%, respectively [30]. The 1991 Bethesda
reporting system is still in use and an effort to review the 2004 Pap
Smear Guide Book is underway.
The Ministry of Health has initiated a project to develop a
centralized database system for both public and private sectors
to determine the feasibility and cost-effectiveness of an organized screening program to reduce the incidence of cervical cancer
through a call-recall system, and to develop a national Pap smear
registry. This project also aims to increase Pap smear coverage
to 75% among women aged 2065 years. The project is currently
undertaken in Klang, Selangor and in Mersing, Johor Baharu with
completion targeted for 2011 [30].
The Malaysian Ministry of Health has taken the initiative to also
develop a National Colposcopic Training program and to evaluate
the role of VIA and cryotherapy as modalities for secondary prevention. With support from WHO, a demonstration project on VIA
and cryotherapy is in its early implementation phase in the low
socioeconomic district of Sik in the northern state of Peninsular
Malaysia.
5.3. The Philippines
The Philippine Department of Health (DOH) has advocated cervical cancer screening, but less than half (42%) of the 389 Philippine
hospitals offer screening and only 8% have dedicated screening clinics. The 2001/2002 WHO Health Survey reported a dismal 7.7% total
Pap smear coverage of Filipino women aged 1869 years [31].
Findings from a 19982000 community-based cross-sectional
study showed that knowledge on cervical cancer was inadequate
[32]. The disease was regarded as anxiety-provoking, and serious
but moderately curable. Only 23% of respondents had received a
Pap smear in which 26.6% of these women were from metropolitan
Manila and 18.5% were from other areas outside of metropolitan
Manila. The women who were more likely to have Pap smears
were married, had more children, had a family history of cancer
or perceived themselves to be at risk for the disease.
In February 2005, the Philippine DOH established a Cervical Cancer Screening Program [33] to initiate an organized nationwide
program that includes sustainable capability building, training,
education, hiring of health workers on proper VIA, Pap smear, cytology, colposcopy, and pathology. Considering low resources, VIA will
be advocated as an alternative screening method for cervical cancer, especially in primary and secondary level health care facilities
without Pap smear capability, by the governmental health and welfare sectors, non-government organizations, professional and civil
societies at the national and local levels. Pap smear with VIA triage,
colposcopy, tissue biopsy, cryosurgery and surgery treatment (total
abdominal hysterectomy (TAH) and total abdominal hysterectomy

M76

E.J. Domingo et al. / Vaccine 26S (2008) M71M79

with bilateral salpingo-oophorectomy (TAHBSO)) will be available

at the secondary levels plus radiotherapy and chemotherapy at the
tertiary level.
Recommended screening guidelines are the following: (1)
women 2555 years old will undergo VIA (with acetic acid wash)
cervical cancer screen at least once every 57 years in areas with no
Pap smear capability, otherwise Pap smear will be used; (2) acetic
acid wash (35%) will be used as the primary screening method at
local health units (rural health units; health centers), district hospitals and provincial hospitals with no Pap smear capability; (3) VIA
will be used as a triage method before Pap smear at district, provincial and regional hospitals with Pap smear capability; (4) positive
or suspicious lesion noted upon screening will be referred immediately; and (5) referral centers for cervical cancer diagnostic tests
and treatment will be established in tertiary facilities.
Although the DOH screening program is not fully implemented
as of yet, sustainability of the program will be ensured through local
nancing, e.g., subsidy from the local government unit or health
facility concerned, Philippine Health nancing, or fee for service
(user fee) scheme. A standard system of recording and reporting will be developed at service delivery facilities in collaboration
with population-based cancer registries. Periodic evaluations will
be done to assess the quality of VIA being done, and cytology-based
centers will be improved and increased as the countrys economics
improve. In order to target women about cervical cancer screenig
and services, there will be an annual public education campaign via
mass media and interpresonal communication within each health
center.
In 2006, the Johns Hopkins Program for International Education
on Gynecology and Obstetrics (JHPIEGO) Global Cervical Cancer
Prevention launched the JHPIEGO Cervical Cancer Prevention Network Program (CECAP) at the Philippine General Hospital Cancer
Institute. The aim of CECAP is to increase education and awareness about cervical cancer in Filipino women and provide them
with access and information to screening and effective treatments
through the single visit approach - VIA screening and treatment
with cryotherapy for those tested positive during the same visit-,
as well as HPV vaccination.
5.4. Thailand
Pap smears have long been used in Thailand for screening of cervical cancer but despite 40 years of implementation, there has been
little impact. In 2000, 33% of women have never been screened in
their lifetime in the Khon Kaen province. Moreover, women with
abnormal smears were likely to be lost to follow-up with primary
reasons being: (1) non-attenders did not receive an appropriate
letter of their results; (2) they did not understand the information provided in the letter; (3) they received a letter indicating that
normal test results; (4) they believed that their results were not
serious; or (5) travel-related issues [34].
There is no organized screening program in Thailand, only
opportunistic screening when attending services such as family
planning, pregnancy counseling, ante- and post-natal clinics or
sexually transmitted disease (STD) clinics [35]. Doctors require a
fee for screening, and some costs may be offset by sporadic campaigns from local health departments or charitable foundations. In
19992001, a pilot study evaluating cytology as a primary screening
test was carried out and the results later formed proposals to the
government for a national screening program. In 2002, the Ministry
of Public Health proposed the goal of screening the entire population between the ages of 3560 years at ve year intervals. In
the rst phase of screening, measures to build capacity for screening with cytology have been initiated, which include training for
nurses, cytologists, as well as additional resources for cryotherapy

and loop electrosurgical excision procedure (LEEP). This involves

providing reimbursements to provincial health authorities for each
examination performed. The program also included public health
education to improve knowledge and awareness on cervical cancer,
education and training of health care workers, competency-based
training for nurse providers, quality assurance and information
management systems.
The 2005 preliminary report showed Pap smear coverage of
67.6% (405,756 women out of 0.6 million women targeted). Of those
screened, 1.6% had abnormal cytology and 0.04% had pre-invasive
and invasive cervical cancer. Among the 0.1 million women targeted for the single visit approach with VIA-cryotherapy, 47,418
women were screened and 810% were offered cryotherapy. The
competency of nurse providers who performed cryotherapy was
satisfactory and women were highly satised with the single visit
approach [34].
Although, the government backed program is largely based on
cytology, other alternative screening strategies considered in Thailand include are (a) VIA-positive but unsuitable for cryotherapy;
or (b) suspected for cervical cancer. Other screening methods or
strategies that are being considered include 1) self-sampling to
increase coverage and compliance, particularly in rural areas where
adequate numbers of physicians or medical personnel may not be
available; 2) mobile clinics for screening, which can reduce the geographic barriers for participation in screening; and 3) increasing the
capacity for HPV testing as an adjunct to cytology. Patients with
abnormal pap smear are also referred to catchment hospitals for
further management. [35].
5.5. Vietnam
Between 1999 and 2004, population-based Pap smear screening
was established in 10 districts in southern and central Vietnam in
women 3055 years of age, in collaboration with the Viet/American
Cervical Cancer Prevention Project [36]. All screening and treatment services are performed by public sector health providers.
In certain districts, decreasing programmatic quality has been
observed with inadequate follow-up of screen-positive women
and poor laboratory performance. In a systems analysis of program deciencies in Vietnam, it was revealed that the target
age group for reproductive health services and screening services barely overlapped, and with the country transitioning into
a market economy, private-sector health provider incomes outpaced increases in public sector incomes, producing incentives
against Pap screening in the public sector. Moreover, this leaves
fewer incentives to follow-up women with cytological abnormalities [36]. From the perspective of the cytotechnologist, they are
often allocated insufcient time to perform their readings of Pap
smears which adversely affects the detection rates of cervical
neoplasia.
Coverage has not exceeded 40% in any Vietnamese district where
population-based Pap screening is currently performed. In the
20012002 WHO Health Survey, total Pap coverage of the general
population of women aged 1869 years was estimated to be 4.9%
[37]. There has been little political will in supporting cervical cancer prevention efforts in Vietnam when there are other competing
health priorities [36].
Recently, the National Target Cancer Control Program of Vietnam has been approved by the Vietnamese Government and will
begin in 2008 and continue through 2010 to 2020 [36,38]. The general objectives of the program are to reduce cancer incidence and
mortality rates, as well as to improve the quality of life for cancer
patients. The specic objectives of the program are: (1) to control
risk factors of cancer such as smoking and other environmental factors; (2) to monitor prevalence, incidence and mortality of cancers

E.J. Domingo et al. / Vaccine 26S (2008) M71M79

such as breast, lung and cervical cancer; (3) to design and conduct
models for early detection of cancer in communities; (4) to improve
awareness on cancer prevention in communities and to strengthen
the capacity of its health care staff at different levels; (5) to establish pain relief and palliative care units at current prevention and
control cancer hospitals; and (6) to design and implement models
for taking care of cancer patients in communities.
Cervical cancer is one of the most common cancers in Vietnamese women and is one important issue that should be
addressed by the National Target Program. Such activities include
screening for early detection, new techniques for diagnosis and
treatment of cervical cancer and formation of a national network
for cancer prevention. The public health approach is to improve
awareness on cervical cancer, train health care staff and improve
health promotion in the communities.
Furthermore, Vietnam has proposed a National Strategy for Cancer Control up to 2020 with the objectives of reducing cervical
cancer mortality rate and decreasing the proportion of advanced
stage cancers from 80% to 50%. The Pap test has been the main
method of screening but VIA is also being explored. However, the
Ministry of Health in collaboration with PATH through a project
supported by the Bill & Melinda Gates Foundation, will implement activities to strengthen secondary cervical prevention that
will include a pilot study evaluating new simple and affordable
screening technologies along with VIA.
6. Cervical cancer prevention and HPV vaccination
6.1. Indonesia
The Leiden University Medical Center (LUMC) European Union
consortium sponsored an HPV pilot program in Indonesia (Jakarta
and Bali). A clinical trial will be conducted among 200 women
examining the feasibility of simple, low-cost delayed type hypersensitivity (DTH) skin test to detect HPV-immune reactivity versus
HPV-16 [39]. This will help determine the proportion exposed to
HPV-16 and provide data as to when the most appropriate age
would be for vaccination.
6.2. Malaysia
The Malaysia Drug Authority approved the use of the quadrivalent HPV vaccine (Gardasil , Merck & Co., Inc., Whitehouse Station,
NJ, USA) in October 2006, but its use is exclusively in private health
centers. Many issues regarding vaccine use remain unanswered
including the cost-effectiveness and long-term benets to a population where the burden of type-specic HPV infection is unknown.
Also unknown is the duration of protection by HPV vaccination, the
need for booster doses, vaccine efcacy in older women, and public perception about the prevention of an STD among sexually nave
girls and boys.
The Department of Community Health at the National University of Malaysia is currently conducting a cost-effectiveness analysis
of HPV vaccination in government hospitals and completion is
expected in 2008. Other studies on the prevalence of HPV and
invasive cervical cancer are also underway.
A National Immunization Technical Committee under the Disease Control Division of the Malaysian Ministry of Health has
been given the responsibility to study and make recommendations
on the role of the HPV vaccine in Malaysia by 2009. Currently,
the Ministry of Health, non-governmental organizations (NGOs)
and pharmaceutical companies are actively involved in increasing
knowledge on HPV and cervical cancer using mass media, media
electronics, posters and pamphlets.

M77

6.3. The Philippines

6.3.1. Vaccine acceptability
Two prophylactic HPV vaccines are registered and marketed in
the Philippines that prevent against HPV types -6, 11, 16 and 18
(Gardasil ) and against types -16 and 18 (CervarixTM , GlaxoSmithKline Biologicals, Rixensart, Belgium).
To determine the acceptability of HPV vaccines in the Philippines, a focus group discussion and exploratory survey was initiated
with 195 women with daughters aged 1215 years recruited
from the Philippines General Hospital Obstetrics-Gynecology charity clinics regarding their knowledge and attitude towards HPV
vaccination [40]. Only 14.4% of those surveyed had heard of
HPV with television being the main source of information and
doctors being the second. Approximately 56.4% of the women
identied HPV as an STD and only 31.8% associated it to the
development of cervical cancer. The HPV vaccine was acceptable to 75.4% of women because it would prevent illness, and
of these more than half (55%) thought it should be given prior
to sexual activity, while 27% thought it should be administered
between 1215 years of age. Many thought that men should
also receive the vaccine to prevent them from infecting their
partners.
Acceptability of the vaccine was higher when respondents were
recruited from the Philippines General Hospital general wards. In
ten mothers aged 2143 years, nine mothers would allow their
children to receive the HPV vaccine even if only one out of ten
knew about it. Likewise, in ten pediatric patients aged 1019 years,
seven would like to receive the vaccine. For those non-acceptors,
the reasons cited were young age, painful injection and sexual inexperience.
Another concern against HPV vaccination is the issue that it
could promote or encourage unsafe sexual behavior among adolescents. However the predominant reason for non-acceptance of
the vaccine is its high cost.
6.3.2. Vaccination policy and delivery
The Philippine Department of Health has not formulated a
policy on HPV vaccination, perhaps stemming from the most controversial concern that such formal policy could have a negative
impact on the sexual behavior of the youth. However, it may be
worthwhile to consider the impressions from the Report Card
HIV Prevention for Girls and Young Women (the Philippines)
[41] as a framework for a prospective Philippine HPV Vaccination Program: (1) minimum legal age at marriage is 18 years;
(2) sex work is illegal but tolerated and common in many areas;
(3) there is no budget allocation for sexual and reproductive
health services, and where such services exist, they tend to be
based on marital status than on age-married youths are regarded
as adults for whom services are acceptable; with discrimination against those who are not married; (4) STI treatment is not
free, neither is voluntary counseling and testing; and available
data suggest that fewer women access STI testing compared to
men.
More young people engage in sex at an earlier age and
often without contraceptions. These issues call for a comprehensive evidence-based sexual and reproductive health program
that takes into consideration the needs of the youth. It should
have a clear guideline, which is national in scope that will
provide young people with access to health services. Commitment to womens health should incorporate HPV vaccination
into the educational curriculum with learning modules to adequately train teachers. The success of HPV prevention for
girls and young women will depend on the political will of
the government, as well as the support from relevant inter-

M78

E.J. Domingo et al. / Vaccine 26S (2008) M71M79

governmental and non-government organizations (NGOs), and

donors.
6.3.3. Research on deployment of HPV vaccination
The current DOH cervical screening program includes Pap
smear, VIA, colposcopy and tissue biopsy in women aged 2555
years [21]. If HPV vaccination is integrated into this program, the
target population should be extended to include girls and women
aged 1124 years, and those who have not been vaccinated or have
not completed the full course.
A national registration system that is linked to a populationbased tumor registry could also be implemented to identify a cohort
of vaccinated women who can be followed up and compared to
unvaccinated cervical cancer cases identied from the tumor registry.
Introduction of an HPV vaccination program can be done
in phases across different regions of the archipelago through
demonstration research projects. Once the program is operational,
evaluation of its short and long-term effects can be done, specifically to evaluate: (1) the knowledge, attitudes, practices and
acceptability of vaccination of the target female population and
health providers before, during and after implementation to capture behavioral changes and caveats to improve the program and
to assess the effectiveness of regular information, education and
communication campaigns; (2) the technical issues on vaccine use
in the eld-vaccine storage, handling, and distribution as well as
a nationwide registry; (3) compliance with the three dose vaccine
regimen; (4) the health economic impact of vaccination with regard
to efcacy and long-term safety, and to include the use of new
vaccines; (5) the effects on sexual-reproductive health demographics of Filipino adolescents; (6) the effects on cervical screening,
although the recommendation for screening has not changed for
women who have been vaccinated; and (7) the impact of HPV vaccination on the incidence of cervical cancer. Evaluation of the HPV
vaccination program should be a spearheaded by the government
with collaborative support from local agencies and international
research organizations.
The DOH has not received a proposal for the inclusion of HPV
vaccination in its relevant public health programs such as the
Expanded Program for Immunization, Womens Health and Safe
Motherhood Program and Cancer Control Program. School-based
programs may be the best way to reach the target youth. In this
regard, the Department of Education, Culture and Sports (DepEd)
may be involved in the HPV vaccination campaign. DepEds Population Education Program includes a curriculum on responsible
sexual behavior and reproductive health care commencing at the
5th grade elementary school level and up to college. To cover
the out-of-school youths that comprise 15% of the 724 year age
group, community-based programs should be the most appropriate
approach.
6.4. Thailand
The quadrivalent vaccine (Gardasil ) has been licensed in
Thailand since March 2007. It is recommended for children and adolescents 917 years of age and women up to age 26 years. Currently,
cost-effectiveness models of HPV vaccination in cancer prevention
and control programs are being studied. A registry of girls and
women who receive the vaccine has been suggested.
6.4.1. Vaccination policy and delivery
Health promotion programs are mostly implemented by public
health sector agencies and NGOs using various approaches including health behavior modication for positive health impact, social
environment modication, congregation for self-help among peo-

ple with the same health problems and individual and community
encouragement for self-care. Some of the implemented programs
and activities are as follows: campaigns on smoking cessation,
physical activity promotion, healthy diet consumption, and healthy
behavior promotion. To date, there is no national HPV vaccination
policy in Thailand.

6.5. Vietnam
6.5.1. Vaccine acceptability
In a recent survey of mothers on general vaccine attitudes and
attitudes toward HPV vaccination, 11% were aware of the HPV vaccine, 94% believed the vaccine will be effective and 90% disagreed
that their daughter would engage in early sex if they were vaccinated [32]. Over 90% of mothers favored vaccination of their
daughters and 95% indicated that recommendation from their doctors would be important for their decision-making process.
Many questions and program concerns have to be addressed in
this country before any vaccine can be effectively used. It is important to ensure equitable access to HPV vaccines in order to attain
high coverage of adolescents before they become sexually active.
For successful implementation of HPV vaccination, a pilot demonstration in at least one community should be done before extending
it nationwide. The health system should be strengthened to adopt
the vaccine, and engagement and support from various stakeholders will be important.

6.5.2. Potential barriers to HPV vaccination

The lack of knowledge on cervical cancer and HPV among the
Vietnamese communities prohibit participation in a vaccination
program. Since the vaccine targets adolescents, this will need to
be integrated into the countrys national immunization program.
In addition, the cost of the vaccine is high which will hinder those
with a low income accessibility. The government still has to discern whether investment on vaccination or nationwide screening
is best.

6.5.3. Vietnam demonstration project on cervical cancer vaccine

A cervical cancer vaccine project supported by PATH will be
conducted in the province of Thaibinh and Dongthap in 2008. The
aim of the project is to identify the most cost-effective strategy
for reaching 1114 year old girls with the HPV vaccine. The results
will be compared between urban and rural areas, and will answer
whether intensive campaigns or minimal efforts should be put into
the campaign.

7. Conclusions
Cervical cancer has remained a leading cancer in women in
Indonesia, Malaysia, the Philippines, Thailand and Vietnam. For
close to ve decades, standard Pap screening has been available
for opportunistic screening in Southeast Asia, but organized programs have yet to be implemented, largely due to high costs and
needs for infrastructure within the health system. Recently, alternatives to Pap smear screening have been introduced in Indonesia,
Malaysia, the Philippines and Thailand, where VIA-cryotherapy
programs are being actively evaluated. HPV vaccination has been
approved in these ve countries with new efforts to integrate primary prevention at the forefront of cervical cancer control. The
socio-cultural, economic and political turmoil and upheavals in this
region may inuence the delivery of vital cervical cancer prevention
campaigns.

E.J. Domingo et al. / Vaccine 26S (2008) M71M79

Disclosed potential conict of interest

EJD: Advisory Board (GlaxoSmithKline, Merck Sharp & Dohme).
CAN: Consultant (Roche Philippines, Inc.); Stockholder (Roche
Philippines, Inc.).
References
[1] Ferlay J, Bray F, Pisani P, Parkin D. GLOBOCAN 2002. Cancer Incidence, Mortality
and Prevalence Worldwide. IARC CancerBase No.5, version 2.0 IARCPress, Lyon,
2004.
[2] Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M, et al. Cancer
Incidence in Five Continents, Vol. IX. IARC Scientic Publications No. 160. Lyon:
IARC Press, 2007.
[3] Curado MP, Edwards B, Shin HR, et al. Cancer Incidence in Five Continents, Vol.
I to VIII. IARC Cancer Base No.7. Lyon: IARC Press, 2005.

[4] Castellsagu X, de Sanjose S, Aguado T, Louie KS, Bruni L, Munoz

J, et al. HPV
and Cervical cancer in the World. 2007 Report. WHO/ICO Information Centre
on HPV and Cervical Cancer (HPV Information Centre). Vaccine 2007; Vol. 25
Supp. 3. Available at: www.who.int/hpvcentre (last accessed: April 2008).
[5] The Second Report of National Cancer Registry. Cancer Incidence in Malaysia
2003. Kuala Lumpur, Malaysia: National Cancer Registry, 2003.
[6] Philippine Cancer Society Manila Cancer Registry and the Department of Health
Rizal Cancer Registry. Philippine Cancer Facts and Estimates. PCSI, 2005.
[7] UP-PGH Department of Obstetrics and Gynecology Staff Conference. Section of
Gynecologic Oncology Annual Report 2006, 2006.
[8] Deerasamee S, Martin N, Sontipong S, Sriamporn S, Sriplung H. Cancer in Thailand. Lyon: IARC Press; 1999. Technical Report No. 34.
[9] Sriplung H., Sontipong S, Martin N. Cancer in Thailand Vol. III, 19951997. Report
No.: 49. Bangkok: National Cancer Institute; 2003.
[10] Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, Winer R, et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical
lesions: a meta-analysis update. Int J Cancer 2007;121(3):62132.
[11] Sriamporn S, Snijders PJ, Pientong C, Pisani P, Ekalaksananan T, Meijer CJ, et al.
Human papillomavirus and cervical cancer from a prospective study in Khon
Kaen, Northeast Thailand. Int J Gynecol Cancer 2006;16(1):2669.
[12] de Boer MA, Vet JN, Aziz MF, Cornain S, Purwoto G, van den Akker BE, et al.
Human papillomavirus type 18 and other risk factors for cervical cancer in
Jakarta, Indonesia. Int J Gynecol Cancer 2006;16(5):180914.
[13] de Sanjose S, Diaz M, Castellsague X, Clifford G, Bruni L, Munoz N, et al.
Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect
Dis 2007;7(7):4539.
[14] Lee LK, Chen PC, Lee KK, Kaur J. Premarital sexual intercourse among adolescents in Malaysia: a cross-sectional Malaysian school survey. Singapore Med J
2006;47(6):47681.
[15] Ngelangel C, Munoz N, Bosch FX, Limson GM, Festin MR, Deacon J, et al. Causes
of cervical cancer in the Philippines: a case-control study. J Natl Cancer Inst
1998;90(1):439.
[16] Sexual & Reproductive Health of Adolescents & Youths in the Philippines - A
Review of Literature & Projects 19952003. Manila: World Health OrganizationWestern Pacic Regional Ofce (WHO-WPRO) 2005; 913.
[17] Chichareon S, Herrero R, Munoz N, Bosch FX, Jacobs MV, Deacon J, et al. Risk
factors for cervical cancer in Thailand: a case-control study. J Natl Cancer Inst
1998;90(1):507.
[18] Ishida WS, Singto Y, Kanjanavirojkul N, Chatchawan U, Yuenyao P, Settheetham
D, et al. Co-risk factors for HPV infection in Northeastern Thai women with
cervical carcinoma. Asian Pac J Cancer Prev 2004;5(4):3836.
[19] Thomas DB, Qin Q, Kuypers J, Kiviat N, Ashley RL, Koetsawang A, et al.
Human papillomaviruses and cervical cancer in Bangkok. II. Risk factors
for in situ and invasive squamous cell cervical carcinomas. Am J Epidemiol
2001;153(8):7329.

M79

[20] Shannon J, Thomas DB, Ray RM, Kestin M, Koetsawang A, Koetsawang S, et al.
Dietary risk factors for invasive and in-situ cervical carcinomas in Bangkok,
Thailand. Cancer Causes Control 2002;13(8):6919.
[21] Sukvirach S, Smith JS, Tunsakul S, Munoz N, Kesararat V, Opasatian O, et al.
Population-based human papillomavirus prevalence in Lampang and Songkla,
Thailand. J Infect Dis 2003;187(8):124656.
[22] Kanato M, Saranrittichai K. Early experience of sexual intercoursea risk factor
for cervical cancer requiring specic intervention for teenagers. Asian Pac J
Cancer Prev 2006;7(1):1513.
[23] Brown AD, Jejeebhoy SJ, Yount KM. Sexual relations among young people in
developing countries; evidence from WHO case studies. Geneva: Department
of Reproductive Health and Research, Family and Community Health, World
Health Organization; 2001.
[24] Pham TH, Nguyen TH, Herrero R, Vaccarella S, Smith JS, Nguyen Thuy TT, et al.
Human papillomavirus infection among women in South and North Vietnam.
Int J Cancer 2003;104(2):21320.
[25] Duong CT, Nguyen TH, Hoang TT, Nguyen VV, Do TM, Pham VH, et al. Sexual
Risk and Bridging Behaviors Among Young People in Hai Phong, Vietnam. AIDS
Behav 2007;12(4):64351.
[26] International ght against cervical cancer. Female Cancer Program 2005. Available at: http://www.femalecancerprogram.org/FCP/ (last accessed: April 2008).
[27] Noviani R. 2-2-0008. Personal Communication.
[28] WHO. World Health Survey 2001/2002. Malaysia. Geneva: World Health Organization; 2002.
[29] The Malaysian Guidebook for PAP Smear Screening. Malaysia: Division of Family
Health Development, Ministry of Health, 2004.
[30] Proposal paper of pilot project on community-based cervical cancer screening
by call-recall system, Family Health Development Division. Ministry of Health
Malaysia 2001:2885.
[31] WHO World Health Survey 2001/2002. Philippines. Geneva: World Health
Organization, 2002.
[32] Dinh TA, Rosenthal SL, Doan ED, Trang T, Pham VH, Tran BD, et al. Attitudes of
mothers in Da Nang, Vietnam toward a human papillomavirus vaccine. J Adolesc
Health 2007;40(6):55963.
[33] Administrative Order No. 20052006. Establishment of a cervical cancer
screening program. Department of Health, Republic of the Philippines 2005
February 10. Available at: http://www.doh.gov.ph/ (last accessed: April 2008).
[34] Linasmita V. Cervical cancer screening in Thailand. FHI-satellite meeting on the prevention and early detection of cervical cancer in the Asia
and the Pacic region. Bangkok, Thailand, February 2006. Available at:
http://www.tgcsthai.com/index2.php?option=com content&do pdf=1&id=46
(last accessed: April 2008).
[35] Sriamporn S, Khuhaprema T, Parkin DM. Cervical cancer screening in Thailand:
an overview. J Med Screen 2006;13(Suppl. 1):S3943.
[36] Suba EJ, Murphy SK, Donnelly AD, Furia LM, Huynh ML, Raab SS. Systems
analysis of real-world obstacles to successful cervical cancer prevention in
developing countries. Am J Public Health 2006;96(3):4807.
[37] WHO. World Health Surveys 2001/2002. Laos. Geneva: World Health Organization; 2002.
[38] The National Target Program on cancer control and cancer prevention. Ministry
of Health, Vietnam 2007.
[39] HPV Pilot Action Indonesia PAHPV-1 (4/15/2004-8/14/2005). The IST
World portal: Internet Communication. Available at: http://www.istworld.org/ProjectDetails.aspx?ProjectId=6fea052aa157419da157d4136c549d
79 (last accessed: April 2008).
[40] Zalameda-Castro CR, Domingo EJ. A hospital-based study on the knowledge and
attitude of mothers of adolescents in the Philippine General Hospital regarding
Human Papillomavirus Infection and its potential vaccine. Philippine J Gynecol
Oncol 2007;4(1):16.
[41] HIV prevention for girls and young women. Report Card Philippines. UNFPA:
Population issues: Preventing HIV infection: HIV Prevention for Girls and
Young Women: Report Cards 2006. Available at: http://www.unfpa.org/
hiv/reportcard.htm (last accessed: April 2008).