Malignant Neoplasm Burden in Nepal - Data from the Seven Major Cancer Service Hospitals for 2012

In Nepal, while no population based cancer registry program exists to assess the incidence, prevalence, morbidity and mortality of cancer, at the national level a number of hospital based cancer registries are cooperating to provide relevant data. Seven major cancer diagnosis and treatment hospitals are involved, including the BP Koirala Memorial Cancer hospital, supported by WHO-Nepal since 2003. The present retrospective analysis of cancer patients of all age groups was conducted to assess the frequencies of different types of cancer presenting from January 1st to December 31st 2012. A total of 7,212 cancer cases were registered, the mean age of the patients being 51.9 years. The most prevalent age group in males was 60-64 yrs (13.6%), while in females it was 50-54 yrs (12.8%). The commonest forms of cancer in males were bronchus and lung (17.6%) followed by stomach (7.3%), larynx (5.2%) and non Hodgkins lymphoma (4.5%). In females, cervix uteri (19.1%) and breast (16.3%), were the top ranking cancer sites followed by bronchus and lung (10.2%), ovary (6.1%) and stomach (3.8%). The present data provide an update of the cancer burden in Nepal and highlight the relatively young age of breast and cervical cancer patients.


Introduction
Hospital. While there is no population based cancer registry program, an initial assessment of incidence was published by Pradhananga et al. in 2009. It is known that approximately 8,000-10,000 cancer deaths annually in Nepal, the most common cancer site in males being the lung, followed by the oral cavity and stomach, while the first three in females were found to be cervix uteri, breast and lung (Mishra et al., 2015). In another survey, ovarian (14%), stomach (14%) and lung (10%) were the main cancer sites, accounting for 38% of the total (Bhandari et al., 2014) The land area of the country is 147,181 sq kms and is bordered by China in the north, and India on all other side. According to census 2011, the population was projected as 29,128,517 in 2012, with 14,621,285 males and 14,507,232 females. About 34.2% of the total population is below 14 years age group and only 15% are above 60 yrs of age. The life expectancy of males is 64.9 and in females is 67.4.The average literacy rate is 65.9% (Central Bureau of Statistics, Nepal). The size of the country, relatively inaccessibility of distant regions and these demographic factors all contribute to difficulties in providing accurate cancer statistics. However, by pooling the cases presenting in the main urban centers, a picture of the essential nature of the problem can be generated on which to base future cancer control activities.

Materials and Methods
In this study the seven major cancer service providing hospitals were BP Koirala Memorial Cancer Hospital as the national cancer hospital in Bharatpur, Bhaktapur cancer hospital, Bir, TU Teaching and Kanti Children Hospitals in Kathmandu and in the east of the country the BPK Institute of Health Science in Dharan and in the west the Manipal Teaching hospital, Pokhara.
All cases diagnosed by a histopathologist, hematologist and/or radiologist and treated for cancer with name, age, sex, occupation, religion, district and diagnosis from January 1st to 31st December 2012 were abstracted from medical record sections in the National cancer registry forms from all hospitals. All forms were collected for analysis and all double/multiple entry cancer cases were excluded by cross checking name, age, sex, address and hospital registered number of each patient and all cases coded as per ICD-O, 3rd edition(Fritz and Percy, 2000). Information on other variables was coded according to the international guidance (Jenson et al, 2003).These codes were converted to ICD-10(1994) for tabulation. Data were entered and analyzed using SPSS 10.1 (SPSS Inc. Chicago, USA) and relative frequency were obtained.

Results
During the study period 7,212 cancer cases were recorded as summarized in Table 1. Overall, female cancer cases (54.4%) were more common than in males (45.6%) (ratio of 1:1.19). Most cancer cases were registered in BP Koirala Memorial Cancer Hospital followed by Bhaktapur Cancer Hospital and Bir Hospital. The number of cases by site (ICD-10) and percentages of various cancer cases for males and females are given in Table. In addition, data for the age distribution of the most   common cancers are given in Figure 1 for males and females, separately. In the youngest age group of 0-15 years, lymphomas and lekemias as well as connective tisue tumours were the most prevalent, as well as nervous tissue lesions. A relatively young age for breast and cervical cancers in females was particularly evident.

Discussion
The results of this retrospective study of cancer data collected for analysis from seven cancer diagnosis and treatment major hospitals from 1st January to 31st December 2012 in Nepal were clearly in line with earlier reports (Pradhananga et al., 2009;Bhandari et al., 2014Mishra et al., 2015. In the Himalayan Institute of Medical Sciences, Dehradun, India with low socio-economic status like in Nepal, the top five cancers in males were lung, larynx, lymphoma, oesophagus and stomach, while in females they were breast, cervix, gallbladder, ovary and oesophagus (Gaur et.al., 2006) Compared to the earlier report from the same hospitals (Pradhananga et al., 2009), in males the percentage rates for trachea/lung and larynx were increased (from 14.6 to 17.6, and 3.7 to 5.2) while those for the buccal cavity appeared decreased (7.8 to 3.7). The latter is in agreement with the general trends within South Asia for reduction over time (Moore et al., 2010). In females, the main change was increase in breast and decrease in cervical cancer rates, again reminiscent of data for India (Moore et al., 2010). Clearly there can a great deal of geographical variation, for example as reported for different regions of India (Nandakumar et al., 2005) and possibility that this might also be the case in Nepal deserves particular exploration. Thus more comprehensive hospital-based registries for regions (eg Binu et al., 2007) might reward investment if geographical origin of patients can be monitored.
Regarding the number one cancer overall, in the lung, this is also the case for many Indian registries and Karachi (Curado et al., 2007;Forman et al., 2012). Unfortunately, we do not have data on the relative incidences of squamous cell carcoma and adenocarcinoma, the former generally predominating in males, presumably because of smoking habits, and the latter in females (Curado et al., 2007;Moore et al., 2010;Forman et al., 2012). A survey among rural communities of Nepal by Pandey et al (1988) showed that in the 20+ yrs age group 85.4% of men and 62.4% of women were tobacco users. The prevalence of smokeless tobacco use, as well as smoking, is high, particularly among males and disadvantaged groups (Sinha et al., 2012). More recently, it was documented that older women are also very likely to smoke, especially those with a lower socioeconomic status (Pandey and Lin, 2013). An inverse association was observed between education and lung cancer risk also observed greater lung cancer risk among unmarried individuals, and lower risk in individuals who lived in the Central region compared to the West (Hashibe et al., 2011). Awareness of lung cancer by tobacco use and other risk factors varied with socioeconomic status amongst residents of Pokhara, Despite their awareness of smoking as a risk factor for lung cancer, most of them still continue to smoke (Chawla et al., 2010). Furthermore, even medical student perceptions about the cause of lung cancer may be influenced by their smoking behavior and there was little knowledge of public health measures for smoking control (Khatiwada et al., 2012). Late presentation leading to advanced disease and poor pulmonary reserves preclude lung cancer resection in most cases (Thapa and Sayami, 2014), so another focus must be on eductaion as to symtpoms for early detection.
The second most common cancer in males was of the larynx, in line with earlier data for Nepal (Lasrado et al., 2012), which was also leading cancer sites in India and Pakistan (Curado et al., 2007;Moore et al., 2010;Forman et al., 2012). In Nepal, the supraglottic larynx is reported to be the commonest subsite to harbor laryngeal malignancy, with smoking and alcohol as prevalent risk factors (Koirala, 2015).
In this study, stomach cancer was also a leading cancer in both males and females. In India there is considerable variation among registries in this cancer (Nandakumar et al., 2005;Moore et al., 2010). Gastric cancer in Nepal is usually diagnosed at an advanced stage and has a poor prognosis, so that early detection is the key to improve the survival (Sah et al., 2015). The relatively low incidence of gastric cancer in Nepal can be attributed to low gastric mucosal atrophy, but mountainous subjects have highrisk gastric mucosal status, which could be considered a high-risk population in Nepal (Miftahussurur et al., 2015).
While cancers of the liver, colorectum (CRC) and prostate appeared rare in the present study, it has been reported CRC among Nepalese young adults accounts for a high proportion. Although right sided colonic cancer has been increasing, rectum is the commonest site (Kansakar and Singh, 2012). Given the association with diabetes mellitus, know to be an increasingly important problem in Nepal (Bhandari et al., 2014), future work should focus more attention on this type of neoplasm. Elevated fasting levels of serum insulin also appear to be associated with a higher risk of prostate cancer in Nepal (Pandeya et al., 2014). While main etiological factors for HCC are HBV, HCV, alcohol and cryptogenic cirrhosis, also the role of elevated insulin level in increasing HCC risk appeared consistent, influencing incidence, risk of recurrence, overall survival, and treatment-related complications in HCC patients in Nepal (Jha et al., 2012;Gupta et al., 2013).
Among females cancer of the cervix uteri is common cancers in the developing countries but in developed countries breast cancer is the leading cancer (Curado et al., 2007;Moore et al., 2010;Forman et al., 2012). There is an urgent need for a reinvigorated and tailored approach to cervix cancer prevention among the educated youth in India, Nepal and Srilanka (Joy et al., 2011). Recent data predict a significant increase in cervical cancer cases in the future, suggesting the need for more focus and resource allocation on cervical cancer screening and treatment . Self-collected sampling methods should be the subject of additional research in Nepal for screening HR-HPV, associated with pre-cancer lesions and cancer, in women in rural areas with limited access to health services (Johnson et al., 2014) In the context of limited screening services in Nepal, the efforts should be to reduce the diagnostic delay especially patient and health care provider delay for early detection and reduction of mortality rate of cervical cancer (Gyenwali et al., 2014) Risk factors for cervix cancer like early age at marriage, early age at first birth, multiparity, poor genital hygiene and infection with HPV virus infection are common in Nepal. Health education programs which are effective not only in increasing knowledge about cervical cancer and pap smear test but also effective in positively changing attitude towards the test should be organized to increase pap smear coverage (Ranabhat et al., 2014).
Breast cancer here proved to have now overtaken cervical cancer in terms of incidence, as in the majority of countries of Asia (Curado et al., 2007;Moore et al., 2010;Forman et al., 2012 ). The fact that young Nepalese women accont for over one quarter of all female breast cancers, many being diagnosed at an advanced stage (Sharma et al., 2005;Thapa et al., 2013) is of particular importance. The level of awareness of breast cancer, including knowledge of warning signs and BSE, is sub-optimal among Nepalese women . low knowledge on breast cancer, risk factors and screening practice among women groups (Shrestha, 2012). Community interventions have been a focus in Bangladesh (Ansink et al., 2008) and Kolkaatta (Basu et al., 2006) and deserve emphaiss in the Nepali context. In both breast and cervical cancer cases compliance with both screening guidelines and subsequent referral and treatment are necessary (Dinshaw et al., 2007a;2007b). It should be noted that breast self examination has been validated in the Nepal setting (Tara et al., 2008).
Our present results claeraly impact on planning and resource allocation for treatment, incuding need for radiotherapy. In Nepal, the cancer cases estimated using a cubic model showed a steady increase in the total frequency of (including male and female cancer cases) following the year 2010  so that demand for different treatment types needs more attention.
In conclusion, in males the incidence of tobacco related cancers and in females, breasts cervix and other gynecological cancer are high in Nepal. Therefore ,primary prevention of lung and other tobacco related cancers by implementation of tobacco control and screening of cervix and breast cancer are necessary on a wider scale from government level. In the absence of population based cancer registry, incidence, prevalence and mortality data are not available, with death certification also not feasible (Kumar and Yeole, 2005), studies like ours provide useful information that can be utilized for health planning in future research.