Rajaraman Swaminathan

Effect of visual screening on cervical cancer incidence and mortality in Tamil Nadu, India: a cluster-randomised trial

BACKGROUND Cervical cancer is the most common cancer among women in developing countries. We assessed the effect of screening using visual inspection with 4% acetic acid (VIA) on cervical cancer incidence and mortality in a cluster randomised controlled trial in India. METHODS Of the 114 study clusters in Dindigul district, India, 57 were randomised to one round of VIA by trained nurses, and 57 to a control group. Healthy women aged 30 to 59 years were eligible for the study. Screen-positive women had colposcopy, directed biopsies, and, where appropriate, cryotherapy by nurses during the screening visit. Those with larger precancerous lesions or invasive cancers were referred for appropriate investigations and treatment. Cervical cancer incidence and mortality in the study groups were analysed and compared using Cox regression taking the cluster design into account, and analysis was by intention to treat. The primary outcome measures were cervical cancer incidence and mortality. RESULTS Of the 49,311 eligible women in the intervention group, 31,343 (63.6%) were screened during 2000-03; 30,958 control women received the standard care. Of the 3088 (9.9%) screened positive, 3052 had colposcopy, and 2539 directed biopsy. Of the 1874 women with precancerous lesions in the intervention group, 72% received treatment. In the intervention group, 274,430 person years, 167 cervical cancer cases, and 83 cervical cancer deaths were accrued compared with 178,781 person-years, 158 cases, and 92 deaths and in the control group during 2000-06 (incidence hazard ratio 0.75 [95% CI 0.55-0.95] and mortality hazard ratio 0.65 [0.47-0.89]). INTERPRETATION VIA screening, in the presence of good training and sustained quality assurance, is an effective method to prevent cervical cancer in developing countries.

Cancer survival in Africa, Asia, and Central America: a population-based study

BACKGROUND Population-based cancer survival data, a key indicator for monitoring progress against cancer, are not widely available from countries in Africa, Asia, and Central America. The aim of this study is to describe and discuss cancer survival in these regions. METHODS Survival analysis was done for 341 658 patients diagnosed with various cancers from 1990 to 2001 and followed up to 2003, from 25 population-based cancer registries in 12 countries in sub-Saharan Africa (The Gambia, Uganda), Central America (Costa Rica), and Asia (China, India, Pakistan, Philippines, Saudi Arabia, Singapore, South Korea, Thailand, Turkey). 5-year age-standardised relative survival (ASRS) and observed survival by clinical extent of disease were determined. FINDINGS For cancers in which prognosis depends on stage at diagnosis, survival was highest in China, South Korea, Singapore, and Turkey and lowest in Uganda and The Gambia. 5-year ASRS ranged from 76-82% for breast cancer, 63-79% for cervical cancer, 71-78% for bladder cancer, and 44-60% for large-bowel cancers in China, Singapore, South Korea, and Turkey. Survival did not exceed 22% for any cancer site in The Gambia; in Uganda, survival did not exceed 13% for any cancer site except breast (46%). Variations in survival correlated with early detection initiatives and level of development of health services. INTERPRETATION The wide variation in cancer survival between regions emphasises the need for urgent investments in improving awareness, population-based cancer registration, early detection programmes, health-services infrastructure, and human resources. FUNDING Association for International Cancer Research (AICR; St Andrews, UK), Association pour la Recherche sur le Cancer (ARC, Villejuif, France), and the Bill & Melinda Gates Foundation (Seattle, USA).

Cancer Incidence in Five Continents: Inclusion criteria, highlights from Volume X and the global status of cancer registration

Cancer Incidence in Five Continents (CI5), a longstanding collaboration between the International Agency for Research on Cancer and the International Association of Cancer Registries, serves as a unique source of cancer incidence data from high‐quality population‐based cancer registries around the world. The recent publication of Volume X comprises cancer incidence data from 290 registries covering 424 populations in 68 countries for the registration period 2003–2007. In this article, we assess the status of population‐based cancer registries worldwide, describe the techniques used in CI5 to evaluate their quality and highlight the notable variation in the incidence rates of selected cancers contained within Volume X of CI5. We also discuss the Global Initiative for Cancer Registry Development as an international partnership that aims to reduce the disparities in availability of cancer incidence data for cancer control action, particularly in economically transitioning countries, already experiencing a rapid rise in the number of cancer patients annually.

Childhood cancers in Chennai, India, 1990-2001: Incidence and survival

Childhood cancers (age at diagnosis: 0–14 years) comprise a variety of malignancies, with incidence varying worldwide by age, sex, ethnicity and geography, that provide insights into cancer etiology. A total of 1,334 childhood cancers registered in population‐based cancer registry, Chennai, India, during 1990–2001 and categorized by International Classification of Childhood Cancer norms formed the study material. Cases included for survival analysis were 1,274 (95.5%). Absolute survival was calculated by actuarial method. Cox proportional hazard model was used to elicit the prognostic factors for survival. The age‐standardized rates for all childhood cancers together were 127 per million boys and 88 per million girls. A decreasing trend in incidence rates with increasing 5‐year age groups was observed in both sexes. The top 5 childhood cancers were the same among boys and girls: leukemias, lymphomas, central nervous system neoplasms, retinoblastomas and renal tumors. The highest 5‐year absolute survival was observed in Hodgkins disease (65%) followed by Wilms tumor (64%), retinoblastomas (48%), non‐Hodgkins lymphomas (47%), osteosarcomas (44%), acute lymphoid leukemia and astrocytoma (39%). Multifactorial analysis of age at diagnosis and sex showed no differences in the risk of dying for all childhood cancers. Completeness of treatment and type of hospital combination emerged as a prognostic factor for survival for all childhood cancers together (p < 0.001), acute lymphoid leukemia (p < 0.001) and non‐Hodgkins lymphoma (p = 0.04). A Childhood Cancer Registry with high‐resolution data collection is advocated for in‐depth analysis of variation in incidence and survival.

Survival from head and neck Cancer in Mumbai (Bombay), India

Head and neck cancers, among the 10 most frequent cancers in the world, are common in regions with a high prevalence of tobacco and alcohol habits. They account for one‐fourth of male and one‐tenth of female cancers in India. The authors report and discuss the survival from these cancers in Mumbai (Bombay), India.

Cancer pattern and survival in a rural district in South India

BACKGROUND Cancer pattern data are rare and survival data are none from rural districts of India. METHODS The Dindigul Ambilikkai Cancer Registry (DACR) covering rural population of 2 millions in Dindigul district, Tamil Nadu state, South India, registered 4516 incident cancers during 2003-2006 by active case finding from 102 data sources for studying incidence pattern, of which, 1045 incident cancers registered in 2003 were followed up for estimating survival. House visits were undertaken annually for each registered case for data completion. Cancer pattern was described using average annual incidence rates and survival experience was expressed by computing observed survival by actuarial method and age-standardized relative survival (ASRS). RESULTS The average annual age-standardized rate per 100,000 of all cancers together was higher among women (62.6) than men (51.9) in DACR. The most common cancers among men were stomach (5.6), mouth (4.2) and esophagus (3.7). Cervical cancer (22.1) was ranked at the top among women followed by breast (10.9) and ovary (3.3). DACR incidence rates were lesser by at least two folds and 5-year survival were on par or lower than Chennai metropolitan registry for most cancers. Five-year age-standardized relative survival (%) in DACR was as follows: all cancers (29%), larynx (48), mouth (42), breast/tongue (38) and cervix (37). CONCLUSION Cancer incidence was significantly lower, cancer patterns were markedly different and population-based cancer survival was lower in rural areas than urban areas thus providing valuable leads in estimating realistic cancer burden and instituting cancer control programs in India.

Education and cancer incidence in a rural population in south India

BACKGROUND Population-based studies describing the association between education and cancer incidence has not yet been reported from India. METHODS Information on the educational attainment of 4417 cancer cases aged 14 years and above, diagnosed during 2003-2006 in Dindigul district, Tamil Nadu, India, was obtained from the Dindigul Ambilikkai Cancer Registry, which registers invasive cancer cases by active methods from 102 data sources. Population distribution by 5-year age groups and for four educational levels namely no education, education <or=5 years, 6-12 years and >12 years, was obtained from census data. Standardized rate ratios based on age-standardized rates were calculated to study cancer risks for different educational levels. RESULTS Men and women with no education had higher overall cancer incidence rates compared to the educated population. The risk of cervix, mouth, esophagus, stomach and lung cancers were inversely associated with higher levels of education whereas a high incidence of breast cancer was observed with increasing educational levels. The standardized rate ratio of cervical cancer 0.32 (95% CI: 0.19-0.52) and of breast cancer was 6.08 (95% CI: 1.81-20.48) for women with more than 12 years of education compared to those with no education. There was paucity of cases in the highest education level for most cancers. CONCLUSION With more and more women in rural India becoming educated, one could foresee breast cancer becoming more frequent even in rural areas of India in future.

Socio Demographic and Reproductive Risk Factors for Cervical Cancer - a Large Prospective Cohort Study from Rural India

BACKGROUND India shows some of the highest rates of cervical cancer worldwide, and more than 70% of the population is living in rural villages. Prospective cohort studies to determine the risk factors for cervical cancer are very rare from low and medium resource countries. The aim of this study was to quantify the effect of risk factors related to cervical cancer in a rural setting in South India. MATERIAL AND METHODS Sociodemographic and reproductive potential risk factors for cervical cancer were studied using the data from a cohort of 30,958 women who constituted the unscreened control group in a randomised screening trial in Dindigul district, Tamilnadu, India. The analysis was accomplished with the Cox proportional hazard regression model. RESULTS Women of increasing age (HR=2.4; 95% CI: 1.6, 3.8 in 50-59 vs 30-39), having many pregnancies (HR=7.1; 1.0, 52 in 4+ vs 0) and no education (HR=0.6; 0.2, 0.7 in high vs none) were found to be at significantly increased risk of cervical cancer. CONCLUSION This cohort study gives very strong evidence to say that education is the fundamental factor among the sociodemographic and reproductive determinants of cervical cancer in low resource settings. Public awareness through education and improvements in living standards can play an important role in reducing the high incidence of cervical cancer in India. These findings further stress the importance of formulating public health policies aimed at increasing awareness and implementation of cervical cancer screening programmes.

Lack of active follow-up of cancer patients in Chennai, India: implications for population-based survival estimates

OBJECTIVE To measure the bias in absolute cancer survival estimates in the absence of active follow-up of cancer patients in developing countries. METHODS Included in the study were all incident cases of the 10 most common cancers and corresponding subtypes plus all tobacco-related cancers not ranked among the top 10 that were registered in the population-based cancer registry in Chennai, India, during 1990-1999 and followed through 2001. Registered incident cases were first matched with those in the all-cause mortality database from the vital statistics division of the Corporation of Chennai. Unmatched incident cancer cases were then actively followed up to determine their survival status. Absolute survival was estimated by using an actuarial method and applying different assumptions regarding the survival status (alive/dead) of cases under passive and active follow-up. FINDINGS Before active follow-up, matches between cases ranged from 20% to 66%, depending on the site of the primary tumour. Active follow-up of unmatched incident cases revealed that 15% to 43% had died by the end of the follow-up period, while the survival status of 4% to 38% remained unknown. Before active follow-up of cancer patients, 5-year absolute survival was estimated to be between 22% and 47% higher, than when conventional actuarial assumption methods were applied to cases that were lost to follow-up. The smallest survival estimates were obtained when cases lost to follow-up were excluded from the analysis. CONCLUSION Under the conditions that prevail in India and other developing countries, active follow-up of cancer patients yields the most reliable estimates of cancer survival rates. Passive case follow-up alone or applying standard methods to estimate survival is likely to result in an upward bias.

Molecular genetics analysis of hereditary breast and ovarian cancer patients in India

BackgroundHereditary cancers account for 5–10% of cancers. In this study BRCA1, BRCA2 and CHEK2*(1100delC) were analyzed for mutations in 91 HBOC/HBC/HOC families and early onset breast and early onset ovarian cancer cases.MethodsPCR-DHPLC was used for mutation screening followed by DNA sequencing for identification and confirmation of mutations. Kaplan-Meier survival probabilities were computed for five-year survival data on Breast and Ovarian cancer cases separately, and differences were tested using the Log-rank test.ResultsFifteen (16%) pathogenic mutations (12 in BRCA1 and 3 in BRCA2), of which six were novel BRCA1 mutations were identified. None of the cases showed CHEK2*1100delC mutation. Many reported polymorphisms in the exonic and intronic regions of BRCA1 and BRCA2 were also seen. The mutation status and the polymorphisms were analyzed for association with the clinico-pathological features like age, stage, grade, histology, disease status, survival (overall and disease free) and with prognostic molecular markers (ER, PR, c-erbB2 and p53).ConclusionThe stage of the disease at diagnosis was the only statistically significant (p < 0.0035) prognostic parameter. The mutation frequency and the polymorphisms were similar to reports on other ethnic populations. The lack of association between the clinico-pathological variables, mutation status and the disease status is likely to be due to the small numbers.