Female-Specific Cancers in Malaysia: A Comprehensive Analysis of Three Decades

INTRODUCTION

Cancer ranks as one of the most common causes of death worldwide, with 8.2 million cancer deaths reported in 2012 [1]. The majority of the deaths were caused by lung, breast, colorectal, stomach, and prostate cancers [2]. However, addressing the cancer context based on gender, there are also a variety of female-specific cancers including female breast, cervical, uterine or corpus uteri or endometrial or placental, ovary, vagina, vulva and fallopian ligament/adnexa cancer. The highest rates of breast cancer in women were observed in European regions and America, where the rates were almost double that of other regions. For cervical cancer, the highest cancer incidence was reported in women from the African region, followed by Southeast Asia, while the lowest rate was observed in the Eastern Mediterranean region [2].

According to GLOBOCAN 2012, the overall cancer incidence rate and overall mortality rate for Asia are lower than developed continents such as North America, Oceania (Australia, New Zealand) and Europe, for both genders [1]. Based on the WHO top five-cancer lists in 2012, the most common female-specific cancers globally are breast and cervical cancer. Breast cancer had the highest mortality rate with 521,000 deaths that year [3]. Southeast Asia ranked second highest for incidences of and mortality from breast cancer of sub-regions in Asia [1]. Epidemiology studies help us to identify the populations that are at the highest risk and to learn about the various genetic and non-genetic risk factors of cancer with the aim of reducing the burden of cancer [3, 4]. It can also assist in early intervention in the form of education, medical care and diagnostics. Some of the interventions include increasing general public awareness, identifying family-based risk for suspected inherited cancer, and providing counseling for high-risk patients [4]. Many cancers have a higher cure rate when detected and reported at an early stage, and cancer treatments are more effective if the cancer is diagnosed early [3, 4].

Malaysia, an upper-middle-income country in Southeast Asia, has a different cancer pattern from the high-income groups in America and Europe. However, Malaysia showed a similar trend when compared to the same income group in Europe and Asia in which lung and breast cancer are the most common cancers among males and females [5]. Malaysia is a multi-ethnic country with a population of 28.3 million in 2010, consisting of 67.4% Bumiputera, 24.6% Chinese, 7.3% Indians and 0.7% other ethnic groups. Among the Malaysian citizens from Peninsular Malaysia and East Malaysia, the Malays are the predominant ethnic group in Peninsular Malaysia, while the Ibans are predominant in Sarawak and the Kadazan/Dusun are predominant in Sabah [6]. The most common female-specific cancer in Malaysia is breast cancer, which show similar trend among all Asian countries [1, 5]. In addition, due to the vast diversity in ethnic groups in Malaysia, it is crucial to observe the patterns of ethnic variation in female-specific cancers so that cancer prevention interventions such as provision of education and screening can be targeted to high-risk groups. Generally, Malaysian women are more susceptible to cancer than men. Female breast cancer was the most prevalent cancer among females, as it accounted for 30-31% cases reported in two consecutive National Cancer Registries. Among all ethnic groups, Chinese had overall higher cancer rates than Malays and Indians. The age group of 30- to 50-year-olds had the highest prevalence of female-specific cancers [7, 8].

This study aims to review epidemiological studies of female-specific cancers in Malaysia. The objectives of this study are:

1. To study the female-specific cancer patterns in this country
2. To identify subgroups in the population (in terms of ethnicity, age, etc.) that are at higher risk of getting female-specific cancers

MATERIALS AND METHODS

Study Design

A systematic review of literatures published on databases from 1^st January 1980 up to 31^st May 2016 was conducted. Studies involving female-specific cancers in Malaysia were identified.

Search Strategy

Relevant studies on female-specific cancers in Malaysia were systematically reviewed by using the Asian Pacific Journal for Cancer Prevention website, and electronic databases including Medline, PubMed, Wiley online library, and ProQuest Central. Included articles were published in any languages and involved all types of trials on patients of all ages between 1980 and 2016 (PRISMA Flow Diagram).

Search Terms

A search was made on PubMed using: (((((((((((((breast cancer) AND Malaysia)) OR ((cervical cancer AND Malaysia)) OR ((uterine cervix cancer) AND Malaysia)) OR ((endometrial cancer) AND Malaysia)) OR ((ovarian cancer) AND Malaysia)) OR ((vagina cancer) AND Malaysia)) OR ((vulva cancer) AND Malaysia)) OR ((placental cancer) AND Malaysia)) OR ((fallopian cancer) AND Malaysia))

Inclusion/Exclusion Criteria

The author included studies that reported the incidences of female-specific cancers in Malaysia, such as cancers of the female breast, cervix uteri, corpus uteri, endometrium, ovary, vagina, vulva, placenta, and fallopian ligament. Studies were excluded if they focused on survival rates, level of awareness, anxiety status of cancer patients, or incidences of cancer screening. The following types of studies were included: reports, prospective studies, retrospective studies, longitudinal studies and record-review studies. However, controlled trials, letters, reviews, opinions, case studies, conference papers, or editorial papers were not included.

Data Extraction

A data extraction form was developed to collect relevant information for articles that met the inclusion criteria. The data extracted included (1) study author names, (2) year of study, (3) study objectives, (4) study design (e.g. reports, prospective studies, retrospective studies, longitudinal studies, and record-review studies), (5) sample size, (6) study population (age and ethnicity), (7) category of cancers, and (8) main findings. Age-standardized incidence, presentation of cancer, lymph node involvement and relative distribution of tumour subtypes are further divided into subcategories of ethnicities.

Data Analysis

All the quantitative data extracted was further analyzed by estimating the risk difference for the types of cancer among different ethnic groups reported across the selected papers. 

RESULTS AND DISCUSSION

There were 76 articles identified after the initial screening and 13 studies were included in this review. In total 63 studies were excluded, for the following reasons: study did not report cancer incidences or female-specific cancers (n = 56); study done was too old (n = 1); study done was not specific to the country, which is Malaysia (n = 2); data available was too limited for extraction (n = 2); and duplication of results reported (n = 2) (Figure 1).

Study Characteristics

The characteristics of the included studies are listed in Table 1. Among the 13 studies, 11 were conducted specifically in Malaysia, one in the ASEAN region [9], and, one in Singapore-Malaysia [10]. 10 studies took place in hospital-based settings, while three are from cancer registries, specifically two from the National Cancer Registry and one from Penang Cancer Registry.

Overall Female-Specific Cancer Incidence

Incidence

According to the GLOBOCAN 2012 report by the International Agency for Research on Cancer (IARC) of the World Health Organisation (WHO), it is estimated that 25.0% of the cancers in Malaysia (9,363 new cases) are female-specific cancers, which is higher than the overall global incidence (19.7%). The 5-year prevalence for female-specific cancers in Malaysia is 38.4%, compared to 29.5% globally [11]. Table 2 provides the incidence, 5-year prevalence, and mortality of female-specific cancers as documented by GLOBOCAN 2012.

The most frequent female-specific cancer among Malaysians was breast cancer (14.5%), followed by cancer of the cervix uteri (5.7%), ovarian cancer (2.9%) and cancer of the corpus uteri (1.9%). When compared with the incidence trend globally, breast cancer (11.9%) and cervical cancer (3.8%) had the same position as Malaysia, namely the top two, but the sequencing for cancer of the corpus uteri (2.3%) and ovarian cancer (1.7%) were slightly different in Malaysia than globally [11].

Stage at Diagnosis and Survival

The survival of patients with breast and cervical cancer is dependent on three main prognostic variables, which are the stage of disease at first diagnosis, the size of the tumor, and the histopathology of cancer [12, 13]. Additionally, breast cancer has another major prognostic variable, which is menstrual status [12]. Breast and cervical cancers are also affected by other underlying factors such as socio-demographic factors (age, ethnicity) and the availability of effective prevention and treatment methods (cancer screening) [12, 13]. Lifestyle factors such as being sexually active tend to reduce the risk of cervical cancer [13].

The overall 5-year survival rates reported for breast and cervical cancers in Malaysia is 49% and 71.1% respectively. Malay women tend to present at the more advanced stage in cancers and have poorer prognosis, which has contributed to them having the lowest survival rate among all three main ethnic groups. Some other factors that may contribute to delayed presentation for cancer treatments are widowers, divorcees, lack of breast self-examination and strong beliefs in traditional medicines [12, 13].

Mortality

The mortality level from female-specific cancers in Malaysia was estimated to be 18.8% of all cancers, comprising 4,058 cases. When compared with the global mortality rate (12.4%), Malaysia has relatively high mortality The top three causes of female cancer deaths both in Malaysia and the world are breast cancer, cervical cancer and ovarian cancer [11].

Four Major Female-Specific Cancers in Malaysia

Breast Cancer

Since 2002, breast cancer has been the most common cancer across all ethnic groups among Malaysian females, and accounted for about 31% of all female-specific cancers [7, 8, 14, 15]. Overall, the lifetime risk for breast cancer among Malaysian women overall was 1 in 20: 1 in 16 for Chinese, 1 in 17 for Indians, and 1 in 32 for Malays [14, 15]. Breast cancer had an average age-standardized rate (ASR) of 48.6 per 100,000 women. Across all studies, Indians had the lowest breast-cancer incidence, then Malays and then the Chinese had the highest incidence. Both Malays and Chinese had more than double the incidence of Indians [7, 8, 14-17]. From 2002 to 2008, the Chinese had the highest ASR with an average of approximately 62 per 100,000 females, Indians 56 per 100,000, and Malays had the lowest incidence with an ASR of 36 per 100,000 females [7, 8, 14-17]. Overall, 80.0% of females had no familial history of breast cancer and had breastfed. More than 50% of breast cancer patients had three or more children [16, 17]. The most common histologic type for breast cancer was infiltrating duct carcinoma, NOS, comprising 84.5% (4522) of all breast cancer cases [14]. Addressing the Malaysian scenario based on age, the incidence of having breast cancer increases in the age group of 50- to 60-year-olds and then declines gradually in the older age groups (Table 3). This trend is slightly different for Malay and Sarawak females where the peak incidence occurs earlier: between the age of 40 and 50 [7, 8, 16, 18].

- = not available, NR = not reported

Age groups are kept as were specified in the original articles, in order to avoid an confusion to the interpreted results.

Quantitative analysis and comparison between the three ethnic groups have further clarified the overall risk difference among the three ethnicities. Comparison between Malays and Chinese revealed that the risk of having breast cancer among Malay women was 20% lower than for Chinese women (-0.20 [-0.21, -0.19]) (Table 4). However, Malay women had a 22.0% higher likelihood of breast cancer than the Indian women (0.22 [0.21, 0.22]) (Table 5). Overall, the risk of breast cancer was noticed to be highest among Chinese women (0.42 [0.41, 0.43]), followed by Malay and Indian women (Tables 4-6). 

Cervical Cancer

In Malaysia, cervical cancer has been ranked second among all female-specific cancers after breast cancer for the past decade [7, 8, 14, 15]. Cervical cancer is also known as the most common cancer of the female reproductive organs [13]. Over 90% of the invasive cervical cancer cases reported were with human papillomavirus (HPV), especially for HPV genotypes 16 and 18 [19]. Overall cervical cancer had an average ASR of 17.3 per 100,000 based on the cancer registry throughout seven years [7, 8, 14, 15]. The Malays had the lowest incidence with an average ASR of 9.8 per 100,000 population from four cancer registry reports, the highest were the Chinese with an ASR of 25 per 100,000, and Indians were in between, with an ASR of 20 per 100,000 [7, 8, 14, 15]. The three national cancer repositories (NCR) reported the incidence increased after the age of 20, peaked in the age group 50- to 59-years-old, and declined after that [7, 8, 14]. Squamous cell carcinoma was the most common histologic type for cervical cancer [14]. Upon further analysis it is revealed that Indians had the lowest risk of developing cervical cancer when compared to Malays (0.22 [0.18, 0.26]) and Chinese (0.46 [0.41, 0.51]), as shown in Tables 4-6. Overall, Chinese women were observed as having the highest risk of cervical cancer.

Ovarian Cancer

In 2002, ovarian cancer was the fourth most-common female-specific cancer in Malaysia, and it dropped to fifth in 2004-2008, making up about 5.0% of all female cancer cases [7, 8, 14, 15]. It reported an average ASR of 7.3 per 100,000 over the seven-year cancer registry. Chinese and Indians reported higher ASRs than Malays, with 8.0, 7.8 and 6.3 respectively. Ovarian cancer was seen in all age groups and the incidence increased sharply after the age of 40 years, and declined at an older age [7, 8, 14]. Serous adenocarcinomas, mucinous cyst adenocarcinoma, and adenocarcinoma, comprising 22.1%, 18.2% and 18.0% of ovarian cases respectively, was the more common morphologic type [14].

Among all three ethnic groups, Indians had the lowest ovarian cancer risk when compared to both Chinese (0.29 [0.27, 0.31]) and Malays (0.36 [0.34, 0.38]) (Tables 4-6). Based on the number of cases reported, the risk difference of ovarian cancer between Chinese and Malay women was 7%. Overall Malay women were at the highest risk of ovarian cancer, followed by Chinese and Indians.

Endometrial Cancer

For the most frequent cancer among Malaysian females, endometrial cancer was ranked seventh in 2002, and then rose to sixth in 2008 [7, 8, 14, 15] from 2002 to 2005, the average ASR for endometrial cancer was 6.5. Among the three main ethnic groups, Indians had the highest seven-year average ASR of 10.0 per 100,000, the Chinese had an ASR of 7.7, and the Malays had the lowest ASR of 3.7. The incidence for endometrial cancer was fairly low before the age of 30 years and increases with age. The incidence peaked between the ages of 60 and 69 and declined thereafter [7, 8, 14]. The most frequent histologic type of endometrial cancer was adenocarcinoma, NOS, comprising 55.3% (390) cases [14].

Further analysis reveales that risk difference for corpus uteri among Malay and Chinese women was (-0.06 [-0.09, -0.03]) (Table 4). Malay women were at least 6% less at risk of carcinoma of corpus uteri. In comparison with Indian women, Malay women were at a higher risk (0.25 [0.23, 0.28]) of having carcinoma of corpus uteri. Like other types of cancer, Chinese women remained at the highest risk of having carcinoma of corpus uteri. Details are shown in Tables 4-6.