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Thermal ablation is a point-of-care ablative treatment technique for cervical intraepithelial neoplasia (CIN). However, limited information is available about its efficacy in low- and middle-income countries. We evaluated the efficacy of thermal ablation in treatment of CIN detected through high-risk human papillomavirus (HPV) screening in China. Women positive on high-risk HPV and having colposcopically suspected lesions eligible for ablation underwent colposcopy, biopsy and thermal ablation in one visit. Women ineligible were recalled for large loop excision of transformation zone (LLETZ) when histopathology results were high-grade CIN. Posttreatment follow-up at 6 months or more was with HPV test and cytology followed by colposcopy and biopsy for HPV and/or cytology-positive women. Cure was defined as either negative cytology and HPV test or absence of histopathology proved CIN in any positive women. Of total 218 HPV-positive women treated with thermal ablation (n = 170) or LLETZ (n = 48), 196 reported for follow-up evaluation. For women with histologically confirmed CIN at baseline (thermal ablation-104; LLETZ-38), cure rates were 84.6% for thermal ablation and 86.8% for LLETZ. Cure rates after thermal ablation were 90.3% for CIN grade one (CIN1) and 76.2% for CIN grade two or worse (CIN2+). HPV clearance rate was 80.4% in women undergoing thermal ablation, which was lower for HPV16/18 compared to other oncogenic types (67.6% vs 85.7%). HPV test had a negative predictive value (NPV) of 98.7% to detect CIN2+ at follow-up and the positive predictive value (PPV) was 40.4%. Thermal ablation is effective to treat CIN as well as to clear the high-risk HPV infection. HPV test has high PPV and NPV in following up patients posttreatment.

Comparable performance indicators for breast cancer screening in the European Union (EU) have not been previously reported. We estimated adjusted breast cancer screening positivity rate (PR) and detection rates (DR) to investigate variation across EU countries. For the age 50-69 years, the adjusted EU-pooled PR for initial screening was 8.9% (cross-programme variation range 3.2-19.5%) while DR of invasive cancers was 5.3/1,000 (range 3.8-7.4/1,000) and DR of ductal carcinoma in situ (DCIS) was 1.3/1,000 (range 0.7-2.7/1,000). For subsequent screening, the adjusted EU-pooled PR was 3.6% (range 1.4-8.4%), the DR was 4.0/1,000 (range 2.2-5.8/1,000) and 0.8/1,000 (range 0.5-1.3/1,000) for invasive and DCIS, respectively. Adjusted performance indicators showed remarkable heterogeneity, likely due to different background breast cancer risk and awareness between target populations, and also different screening protocols and organisation. Periodic reporting of the screening indicators permits comparison and evaluation of the screening activities between and within countries aiming to improve the quality and the outcomes of screening programmes. Cancer Screening Registries would be a milestone in this direction and EU Screening Reports provide a fundamental contribution to building them.

Human papillomavirus (HPV) test, self-sampling and thermal ablation for cervical intraepithelial neoplasia (CIN) have been developed separately to increase screening coverage and treatment compliance of cervical cancer screening programmes. A large-scale study in rural China screened 9,526 women with their combinations to explore the optimal cervical cancer-screening cascade in the real-world. Participants received careHPV and polymerase chain reaction (PCR) HPV tests on self-collected samples. Women positive on either HPV test underwent colposcopy, biopsy and thermal ablation in a single visit. Samples positive on either HPV test were retested for genotyping. Absolute and relative performance of HPV tests, triage strategies, 'colposcopy and thermal ablation' approach were statistically evaluated. PCR HPV test detected 33.3% more CIN grade two or worse (CIN2+) at a cost of 28.1% more colposcopies compared to careHPV. Sensitivities of PCR HPV and careHPV tests to detect CIN2+ were 96.7 and 72.5%. Specificities for the same disease outcome were 82.1 and 86.0%. Triaging HPV-positive women with HPV16/18 genotyping considerably improved the positive predictive value for CIN2+ (4.8-5.0 to 18.2-19.2%). Ninety-six women positive on HPV and having abnormal colposcopy were eligible for thermal ablation and all accepted same-day treatment, contributing to 64.6% being treated appropriately (CIN1+ on histopathology), which reached up to 84.8% among women positive on HPV 16/18 triage. No serious side-effects/complications were reported. The combination of PCR HPV test followed by HPV 16/18 triaging on self-collected samples and colposcopy of triage positive women followed by immediate thermal ablation might be the appropriate screening cascade for rural China.

We report the incidence of cervical intraepithelial neoplasia (CIN) among HIV-infected women who did not have any colposcopic or histopathological evidence of CIN at baseline. Of the 1,023 women without any CIN at baseline, 855 (83.6%) have been followed up to a maximum of 6.4 years contributing 2,875 person years of observation (PYO). Among these 855 women, 54 cases of any CIN were observed resulting in incidence rate of any CIN of 1.9 per 100 PYO. The median time for follow-up for women with any CIN was 3.0 (IQR 1.6-3.7) years. The cumulative incidence rate per 100 PYO of CIN 2 or worse lesion in women with HPV-18 infection at baseline was 13.3% (95% CI 5.1-26.8); in women with HPV-16 infection was 10.8% (95% CI 4.4-20.9); in women with HPV-31 infection was 4.2% (95% CI 0.9-11.7); and in women with other high-risk HPV infections was 5.4% (95% CI 2.6-9.7). HPV-18 infection at baseline contributed highest frequency of incident CIN 2 or worse lesions followed by HPV-16 infection; however, other high-risk HPV types were also responsible for substantial number of incident CIN. The elevated risk of CIN2+ disease in the study cohort was non-significant in women with CD4 count

Breast Cancer Screening Program was introduced and rolled out in Morocco in 2010. Women between 40 and 69 years are screened at the primary health centers (PHC) with clinical breast examination (CBE). A comprehensive evaluation of the program was conducted in 2016–2017 for quality assurance and mid‐term course correction. The evaluation process involved: in‐depth interviews of program managers; focus group discussions with service‐providers of screening, diagnosis and treatment; supportive supervisory visits to randomly selected PHCs and diagnostic centers; desk review of the national guidelines and other published documents; and analysis of the performance data compiled by the program‐in‐charge. We found that the program has strong political support, a well‐organized management structure and documented national policy and protocol. In absence of a mechanism to identify and invite the eligible women individually, the program is opportunistic in nature. Every PHC is provided with an annual target to be screened. A highly visible annual campaign to educate and motivate women has a major impact on participation. Record keeping and data collection are paper‐based. In the years 2015 and 2016, 1.1 and 1.5 million women were screened, respectively. In the year 2015, 62.8% of the annual target population was covered, CBE positivity was 3.2%, a further assessment rate of screen‐positive women was 34.1% and the breast cancer detection rate was 1.0/1000 women. Systematic paper‐based data collection enabled the assessment of some of the process and outcome indicators. The screening coverage was moderate and the cancer detection rate was low., What's new? The rising incidence of breast cancer is a tremendous public health challenge in the developing world. Clinical breast examination is a promising approach provided effective diagnosis, timely treatment, and adequate resources. Here, the authors conducted a comprehensive evaluation of the Breast Cancer Screening Program in Morocco, where systematic data collection is challenging in absence of a computerized information system. They found that the program has strong political support and a well‐organized management structure. Systematic paper‐based data collection showed a moderate screening coverage and low cancer detection rate. The experience will be useful for all developing countries implementing clinical breast examination.

The second report on the implementation status of cancer screening in European Union (EU) was published in 2017. The report described the implementation status, protocols and organization (updated till 2016) and invitation coverage (for index year 2013) of breast, cervical and colorectal cancer screening in the EU. Experts in screening programme monitoring (N=80) from the EU Member States having access to requisite information in their respective countries provided data on breast, cervical and colorectal cancer screening through online questionnaires. Data was collected for screening performed in the framework of publicly mandated programmes only. Filled in questionnaires were received from 26 Member States for all three sites and from one Member State for breast cancer only. Substantial improvement in screening implementation using population-based approach was documented. Among the age-eligible women, 94.7% were residents of Member States implementing or planning population-based breast cancer screening in 2016, compared to 91.6% in 2007. The corresponding figures for cervical cancer screening were 72.3% and 51.3% in 2016 and 2007 respectively. Most significant improvement was documented for colorectal cancer screening with roll-out ongoing or completed in 17 Member States in 2016, compared to only five in 2007. So the access to population-based screening increased to 72.4% of the age-eligible populations in 2016 as opposed to only 42.6% in 2007. The invitation coverage was highly variable, ranging from 0.2%-111% for breast cancer, 7.6%-105% for cervical cancer and 1.8%-127% for colorectal cancer in the target populations. In spite of the considerable progress, much work remains to be done to achieve optimal effectiveness. Continued monitoring, regular feedbacks and periodic reporting are needed to ensure the desired impacts of the programmes. This article is protected by copyright. All rights reserved.

E6 oncoprotein is a necessary agent of HPV driven oncogenic transformation. This study is aimed at evaluating the risk stratification potency of HPV 16/18 E6 oncoprotein (E6) as a triage method for HPV positivity. Moreover, it also acts as a predictor of cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The screening cohort of 1,997 women was followed for a 15 year period in approximate five-year intervals. Participants were concurrently screened by HPV DNA testing (HC2), liquid based cytology (LBC), visual inspection with acetic acid (VIA), and were referred to colposcopy and biopsy if any tests reflected positive. E6 was performed on cervical samples collected from this cohort in 2005 and 2014. The ability of E6 to predict CIN3+ risk after the five and ten year interval was evaluated. Among HPV positive women in 2005, E6 indicated the lowest positive rate (9.9%) compared to LBC (48.4%) and VIA (28.0%), however, a higher prevalence rate (10.3%) and ten year cumulative incidence rate (53.0%) of CIN3+ were detected among women who were E6 positive. Meanwhile, only approximately 4.2% and 2.9% of women with abnormal LBC and positive VIA were diagnosed as prevalent CIN3+ in 2005, 23.0% and 16.5% developed to CIN3+ after year ten, respectively. Strong associations were found between precedent and subsequent HPV persistence and E6 oncoprotein expression (ORadjusted=40.0 and 21.2 respectively). E6 oncoprotein can serve as a low-cost, highly specific, strongly indicative point-of-care method in the triage and treatment of HPV positive women. This article is protected by copyright. All rights reserved.

Mucosal high-risk (HR) human papillomaviruses (HPV) cause a subset of head and neck cancers (HNC). The HPV-attributable fraction of HNC varies substantially between countries. Although HNC has a very high incidence in the Indian subcontinent, information on the contribution of HPV infection is limited. Here, we evaluated the HPV-attributable fraction in HNC (N = 364) collected in a central region of India. HNC from three different anatomical subsites were included, namely, oral cavity (n = 252), oropharynx (n = 53) and hypopharynx/larynx (n = 59). In this retrospective study, HPV-driven HNC were defined by presence of both viral DNA and RNA. Overexpression of p16INK4a was also evaluated. HR-HPV DNA was detected in 13.7% of the cases; however, only 2.7% were positive for both HPV DNA and RNA. The highest percentage of HPV DNA/RNA double positivity was found in oropharynx (9.4%), followed by larynx (1.7%) and oral cavity (1.6%) (p = 0.02). More than half of HPV DNA/RNA-positive cases were p16INK4a -negative, while a considerable number of HPV RNA-negative cases were p16INK4a -positive (17.9%). HPV16 was the major type associated with HNC (60.0%), although cases positive for HPV18, 35 and 56 were also detected. Our data indicate that the proportion and types of mucosal HR-HPV associated with HNC in this central Indian region differ from those in other (developed) parts of the world. This may be explained by differences in smoking and/or sexual behaviour compared with North America and northern Europe. Moreover, we show that p16INK4a staining appeared not to be a good surrogate marker of HPV transformation in the Indian HNC cases.

Visual inspection after acetic acid application (VIA) and human papillomavirus (HPV) detection tests have been recommended to screen women for cervical cancer in low and middle income countries. A demonstration project in rural India screened 39,740 women with both the tests to compare their accuracies in real population setting. The project also evaluated the model of screening women in the existing primary health care facilities, evaluating the screen positive women with colposcopy (and biopsy) in the same setup and recalling the women diagnosed to have disease for treatment at tertiary center. Accuracy of VIA and HPV test used sequentially was also studied. VIA was performed by trained health workers and Hybrid Capture II (HC II) assay was used for oncogenic HPV detection. Test positivity was 7.1% for VIA and 4.7% for HC II. Detection rate of CIN 3+ disease was significantly higher with HC II than VIA. Sensitivities of VIA and HC II to detect 162 histology proved CIN 3+ lesions were 67.9 and 91.2%, respectively after adjusting for verification bias. Specificity for the same disease outcome and verification bias correction was 93.2% for VIA and 96.9% for HC II. Triaging of VIA positive women with HPV test would have considerably improved the positive predictive value (4.0 to 37.5% to detect CIN 3+) without significant drop in sensitivity. All VIA positive women and 74.0% of HC II positive women had colposcopy. There was high compliance to treatment and significant stage-shift of the screen-detected cancers towards more early stage.

The second report on the implementation status of cancer screening in European Union (EU) was published in 2017. The report described the implementation status, protocols and organization (updated till 2016) and invitation coverage (for index year 2013) of breast, cervical and colorectal cancer screening in the EU. Experts in screening programme monitoring (N = 80) from the EU Member States having access to requisite information in their respective countries provided data on breast, cervical and colorectal cancer screening through online questionnaires. Data was collected for screening performed in the framework of publicly mandated programmes only. Filled in questionnaires were received from 26 Member States for all three sites and from one Member State for breast cancer only. Substantial improvement in screening implementation using population-based approach was documented. Among the age-eligible women, 94.7% were residents of Member States implementing or planning population-based breast cancer screening in 2016, compared to 91.6% in 2007. The corresponding figures for cervical cancer screening were 72.3 and 51.3% in 2016 and 2007, respectively. Most significant improvement was documented for colorectal cancer screening with roll-out ongoing or completed in 17 Member States in 2016, compared to only five in 2007. So the access to population-based screening increased to 72.4% of the age-eligible populations in 2016 as opposed to only 42.6% in 2007. The invitation coverage was highly variable, ranging from 0.2-111% for breast cancer, 7.6-105% for cervical cancer and 1.8-127% for colorectal cancer in the target populations. In spite of the considerable progress, much work remains to be done to achieve optimal effectiveness. Continued monitoring, regular feedbacks and periodic reporting are needed to ensure the desired impacts of the programmes.

Although virtually all cervical cancers and most cervical intraepithelial neoplasia (CIN) are caused by persistent human papillomavirus (HPV) infection, only a small proportion of HPV-positive women have or will develop CIN. Triaging HPV-positive women has been suggested to reduce the false-positive rate and proportion of women referred for CIN confirmation and/or treatment. In two cross-sectional studies and one randomized trial in India, we evaluated the impact of using cytology or visual inspection with acetic acid (VIA) to triage HPV-positive women on the proportion of women who would be referred for CIN confirmation and on the detection rates of high-grade CIN. We present the numbers of HPV test-positive women found and the CIN detected among them. We further assess the proportions that would be referred for CIN confirmation with colposcopy/biopsy and CIN that would be detected if cytology triage or VIA triage were used. Using cytology triage at atypical squamous cells of undetermined significance threshold or VIA triage reduced referrals for colposcopy by about 62% and 59%, respectively (p-value = 0.012), but missed around 16% and 18%, respectively, of the high-grade CIN (p-value = 0.539) indicating similar performance of both triaging approaches. The choice of a triage test in different low- and middle-income countries (LMIC) would depend on the availability and affordability in the particular setting. Cytology triage may be considered in settings where adequate infrastructure exists, whereas VIA triage may be suitable in settings with limited or no cytology infrastructure.

E6 oncoprotein is a necessary agent of HPV driven oncogenic transformation. This study is aimed at evaluating the risk stratification potency of HPV 16/18 E6 oncoprotein (E6) as a triage method for HPV positivity. Moreover, it also acts as a predictor of cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The screening cohort of 1,997 women was followed for a 15 year period in approximate five-year intervals. Participants were concurrently screened by HPV DNA testing (HC2), liquid based cytology (LBC), visual inspection with acetic acid (VIA) and were referred to colposcopy and biopsy if any tests reflected positive. E6 was performed on cervical samples collected from this cohort in 2005 and 2014. The ability of E6 to predict CIN3+ risk after the five- and ten-year interval was evaluated. Among HPV positive women in 2005, E6 indicated the lowest positive rate (9.9%) compared to LBC (48.4%) and VIA (28.0%), however, a higher prevalence rate (10.3%) and 10-year cumulative incidence rate (53.0%) of CIN3+ were detected among women who were E6 positive. Meanwhile, only 4.2% and 2.9% of women with abnormal LBC and positive VIA were diagnosed as prevalent CIN3+ in 2005, 23.0% and 16.5% developed to CIN3+ after year 10, respectively. Strong associations were found between precedent and subsequent HPV persistence and E6 oncoprotein expression (OR

Infection with High-risk Human Papillomavirus (HR-HPV) is transient and clears on its own in majority of the women. Only a few women who have persistent infection may finally develop Cervical Intraepithelial Neoplasia (CIN) or cervical cancer in later years. The risk of progression in the HR-HPV positive women with normal cervix or low grade lesion on colposcopy and histopathology at baseline is less studied. We performed a longitudinal study on 650 HR-HPV positive women with colposcopy and/or histopathology proved normal or CIN1 diagnosis at baselineto assess the cumulative risk of development of high-grade CIN. After a mean follow up of 2.1 PYO (range 0.1-5.1) the cumulative incidence of CIN2+ (6.4%; 3.0/100 PYO) was significantly higher in women who had persistent HR-HPV infection compared to those who cleared the infection (adjusted HR 6.28; 95%C.I. 2.87-13.73). The risk of viral persistence in women aged 50-60 years was 2 times higher compared to women aged 40-49 years,and 3 times higher compared to women aged 30-39 years. The probability of having persistent infection increased progressively with higher viral load at baseline (adjusted HR 3.29, 95%C.I. 2.21-4.90 for RLU ≥100; adjusted HR 2.69, 95%C.I. 1.71-4.22 for RLU 10-100). Women with increasing viral load at follow up had four times higher risk of developing CIN2 or worse lesions as compared to those with decreasing load (20.9% vs. 4.8%; p

Cervical cancer is the main cancer among women in sub-Saharan Africa, India and other parts of the developing world. Evaluation of screening performance of effective, feasible and affordable early detection and management methods is a public health priority. Five screening methods, naked eye visual inspection of the cervix uteri after application of diluted acetic acid (VIA), or Lugol's iodine (VILI) or with a magnifying device (VIAM), the Pap smear and human papillomavirus testing with the high-risk probe of the Hybrid Capture-2 assay (HC2), were evaluated in 11 studies in India and Africa. More than 58,000 women, aged 25-64 years, were tested with 2-5 screening tests and outcome verification was done on all women independent of the screen test results. The outcome was presence or absence of cervical intraepithelial neoplasia (CIN) of different degrees or invasive cervical cancer. Verification was based on colposcopy and histological interpretation of colposcopy-directed biopsies. Negative colposcopy was accepted as a truly negative outcome. VIA showed a sensitivity of 79% (95% CI 73-85%) and 83% (95% CI 77-89%), and a specificity of 85% (95% CI 81-89%) and 84% (95% CI 80-88%) for the outcomes CIN2+ or CIN3+, respectively. VILI was on average 10% more sensitive and equally specific. VIAM showed similar results as VIA. The Pap smear showed lowest sensitivity, even at the lowest cutoff of atypical squamous cells of undetermined significance (57%; 95% CI 38-76%) for CIN2+ but the specificity was rather high (93%; 95% CI 89-97%). The HC2-assay showed a sensitivity for CIN2+ of 62% (95% CI 56-68%) and a specificity of 94% (95% CI 92-95%). Substantial interstudy variation was observed in the accuracy of the visual screening methods. Accuracy of visual methods and cytology increased over time, whereas performance of HC2 was constant. Results of visual tests and colposcopy were highly correlated. This study was the largest ever done that evaluates the cross-sectional accuracy of screening tests for cervical cancer precursors in developing countries. The merit of the study was that all screened subjects were submitted to confirmatory investigations avoiding to verification bias. A major finding was the consistently higher sensitivity but equal specificity of VILI compared with VIA. Nevertheless, some caution is warranted in the interpretation of observed accuracy measures, since a certain degree of gold standard misclassification cannot be excluded. Because of the correlation between visual screening tests and colposcopy and a certain degree of over-diagnosis of apparent CIN2+ by study pathologists, it is possible that both sensitivity and specificity of VIA and VILI were overestimated. Gold standard verification error could also explain the surprisingly low sensitivity of HC2, which contrasts with findings from other studies.

Recent studies have suggested role of diabetes mellitus in the development of periodontal diseases, oral inflammatory and neoplastic lesions. We analysed data from randomised oral cancer screening trial in Kerala, India, to study the association between chronic diseases in general, diabetes mellitus in particular, and pre-malignant oral lesions and conditions. A total of 927 subjects with oral leukoplakia, 170 with oral submucous fibrosis, 100 with erythroplakia lesions and 47,773 apparently healthy subjects constituted the cases and controls respectively for our present study. The odds ratio (OR) for oral leukoplakia among women with a history of diabetes mellitus was found to be 2.0 (95% confidence interval (CI) = 1.4-2.9) whereas that for erythroplakia was 3.2 (95% CI = 1.3-7.9), after adjusting for potential confounders. No statistically significant association between diabetes mellitus and oral submucous fibrosis and pre-cancerous lesions/conditions in men was found. An association between diabetes mellitus and pre-malignant oral lesions among women has been observed in our study, although the underlying mechanisms are not clear. This needs to be further evaluated in other settings.

The cost and cost effectiveness of screening previously unscreened women by VIA, cytology or HPV testing was investigated within a large cluster randomised trial involving 131,178 women in rural India. All resources involved in implementation, training, management, recruitment, screening and diagnosis were identified and costed. We estimated the total costs and detection rates for each cluster and used these data to calculate an average cluster cost and detection rate for each screening approach. These estimates were combined to estimate a cost per case of cervical intraepithelial neoplasia grade 2/3 or invasive cancer (CIN 2/3+) detected. The average total costs per 1,000 women eligible for screening were US dollar 3,917, US dollar 6,609 and US dollar 11,779 with VIA, cytology and HPV respectively. The cost of detecting a case of CIN2/3+ using VIA was dollar 522 (95% CI dollar 429- dollar 652). Our results suggest that more CIN2/3+ cases would be detected in the same population if cytology were used instead of VIA and each additional case would cost US dollar 1065 (95% CI dollar 713- dollar2175). Delivering cervical cancer screening is potentially expensive in a low-income country although costs might be lower outside a trial setting. We found screening with VIA to be the least expensive option, but it also detected fewer cases of CIN2/3+ than other methods; its long-term cost-effectiveness will depend on the long-term benefits of early detection. Cytology was more effective at detecting cases than VIA but was also more expensive. Our findings indicate that HPV may not be a cost effective screening strategy in India at current consumable prices.

Visual inspection-based screening tests, such as visual inspection with 4% acetic acid (VIA) and with Lugol's iodine (VILI), have been proposed as alternatives to cytology in mass screening programs. To date, there is only limited information on the accuracy of these tests in detecting High-grade Squamous Intraepithelial Lesions (HSIL). Eleven cross-sectional studies involving 56,939 women aged 25-65 years were conducted in Burkina Faso, Congo, Guinea, India, Mali and Niger to evaluate the accuracy of VIA and VILI performed by health workers. A common protocol and questionnaire was used. For final diagnosis, all women were investigated with colposcopy and biopsies were taken when necessary. Data from the studies were pooled to calculate sensitivity, specificity and predictive values of the tests for the detection of HSIL. Of the screened women, 16.1% and 16.4% were positive on examination using, respectively, VIA and VILI; 1,063 were diagnosed with HSIL. The pooled sensitivity, specificity, positive and negative predictive values for VIA were 76.8% (95% CI: 74.2-79.4%), 85.5% (95% CI: 85.2-85.8%), 9.4% (95% CI:8.8-10.8%) and 99.5% (95% CI:99.4-99.6%), respectively. The values were 91.7% (95% CI: 89.7-93.4%), 85.4% (95% CI: 85.1-85.7%), 10.9% (95% CI: 10.2-11.6%) and 99.8% (95% CI:99.7-99.9%), respectively for VILI. The range of sensitivity and specificity for VIA was 56.1-93.9% and 74.2-93.8%, respectively, between studies and were 76.0-97.0 % and 73.0-91.3% for VILI. VILI had a significantly higher sensitivity than VIA in detecting HSIL, but specificity was similar. VILI appears to be a more accurate visual test for use in screening and treatment programs in low-resource settings.

The knowledge that cervical neoplasia are caused by human papillomavirus (HPV) infection has led to the evaluation of its role in screening. We evaluated the accuracy of HPV testing by Hybrid capture II (HC II) method in detecting cervical intraepithelial neoplasia grade 2 and 3 (CIN 2 and 3) lesions in 4 cross-sectional studies with common protocol and questionnaire in 3 different locations (Kolkata, Mumbai and Trivandrum) in India. These studies involved 18,085 women aged 25-65 years. The reference standard for final diagnosis was a combination of colposcopy/biopsy. All women were investigated with colposcopy and 3,116 received directed biopsy. The sensitivity of HPV testing for detecting CIN 2-3 lesions varied from 45.7% to 80.9% across the study sites; the specificity varied from 91.7% to 94.6% and the positive predictive value from 6.7% to 13.7%. Retesting of 298 randomly chosen denatured samples in France revealed an agreement rate of 85.9% and a kappa-value of 0.72. Although HPV testing seems to be a promising approach for cervical cancer prevention, a large range in sensitivity was observed in our study, possibly due to variations in the quality of specimen collection and reference standards. A higher sensitivity was associated with the center performing the test well. Further developments in terms of more reproducible, less expensive and less sophisticated testing are essential to make the test feasible and effective in low-resource settings.

Simple and inexpensive methods based on visual examination of the cervix are currently being investigated as alternative methods of cervical screening. The test characteristics of visual inspection with 4% acetic acid (VIA), and Lugol's iodine (VILI) and conventional cytology were investigated in a cross-sectional study involving 4,444 women aged 25 to 65 years in Kerala, India. While detection of any acetowhite area constituted a low-threshold positive VIA, detection of well-defined, opaque acetowhite lesions close to or touching the squamocolumnar junction constituted a high-threshold positive VIA test. Detection of definite yellow iodine nonuptake areas in the transformation zone close to or touching the squamocolumnar junction constituted a positive VILI test. Cytology was considered positive if reported as atypia or worse lesions. All screened women were evaluated by colposcopy and biopsies were directed in 1,644 women (37.0%), which allowed the direct estimation of sensitivity, specificity and predictive values. The reference diagnosis was based on a combination of histology and/or colposcopy. True disease status was defined as CIN 2 and worse lesions. A total of 149 (3.4%) women had CIN 2 or worse lesions. The sensitivities of low-threshold VIA, high-threshold VIA, VILI and cytology to detect CIN 2 or worse disease were 88.6%, 82.6%, 87.2% and 81.9%, respectively; the corresponding specificities were 78.0%, 86.5%, 84.7% and 87.8%. Our results indicate that VIA and VILI are suitable alternate screening tests to cytology for detecting cervical neoplasia in low-resource settings.

Younger women who develop breast cancer are hypothesized to have poorer survival rates than women who develop it at a later stage in life. Several studies have suggested that differences in biologic characteristics of breast cancer in younger (premenopausal) and older (postmenopausal) women may account for the prognostic variation. This population-based cohort study reports on survival rates of breast cancer in Singapore and examines the hypothesis that younger breast cancer patients have a poorer prognosis. A total of 6,397 breast cancer patients diagnosed from 1968 to 1992 were identified from the population-based cancer registry and followed up through 1997. Outcome measures were relative survival rates (RSRs) calculated using Hakulinen's method and excess hazards ratios (HRs) derived from a regression model based on relative survival. The 2-, 5- and 10-year RSRs were worse among those aged > 75 (65%, 48% and 39%, respectively). The best survival rates were seen among those aged 40–44 (84%, 67% and 56%). Patients younger than 35 years faired reasonably well (79%, 60% and 50%). When the data were stratified according to clinical stage and calendar year, the highest risk of excess deaths was found in women ≥ 75 years old. In patients with localized cancer and/or regional metastases, those in the 35–39 age group had the lowest excess risk. In patients with distant metastases, those younger than 35 years of age had the lowest excess risk of death. At the population level, younger women (< 45 years) with breast cancer in Singapore have higher relative survival rates. © 2003 Wiley-Liss, Inc.

Since the 1980s, colorectal cancer incidence in Singapore has ranked second to lung in males and females. We describe a population-based analysis of survival of colorectal cancer patients diagnosed from 1968 to 1992 in Singapore. Data of colorectal cancer patients diagnosed during 1968–1992 were retrieved from the Singapore Cancer Registry. Patients were passively followed up for death to the end of 1997. The final dataset consisted of 10,114 subjects. Observed and relative survival rates were calculated by stage (localized, regional metastases and distant metastases), age, ethnicity and calendar period for both genders. Over the study period, a significant progress in survival of colorectal cancer patients was observed. For localized cancer of the colon, the 5-year age-standardized relative survival (ASRS) increased from 36% in 1968–1972 to 66% in 1988–1992 for males and from 32 to 71% for females. For localized rectal cancer, the 5-year ASRS improved from 25 to 66% for males and from 23 to 66% in females. Similarly, improvement was observed in colorectal cancer patients with regional metastases, but not in those with distant metastases. Calendar year period and clinical stage of disease were identified as major significant prognostic factors of survival for colorectal cancer. The substantially improved colorectal cancer survival rates reflected the interplay of cancer control activities in various areas, such as health promotion, early diagnosis and treatment. Our study shows a unique changing pattern of survival experience for colorectal patients from a country undergoing rapid economic development. © 2002 Wiley-Liss, Inc.

Visual inspection after acetic acid application (VIA) and human papillomavirus (HPV) detection tests have been recommended to screen women for cervical cancer in low and middle income countries. A demonstration project in rural India screened 39,740 women with both the tests to compare their accuracies in real population setting. The project also evaluated the model of screening women in the existing primary health care facilities, evaluating the screen positive women with colposcopy (and biopsy) in the same setup and recalling the women diagnosed to have disease for treatment at tertiary center. Accuracy of VIA and HPV test used sequentially was also studied. VIA was performed by trained health workers and Hybrid Capture II (HC II) assay was used for oncogenic HPV detection. Test positivity was 7.1% for VIA and 4.7% for HC II. Detection rate of CIN 3+ disease was significantly higher with HC II than VIA. Sensitivities of VIA and HC II to detect 162 histology proved CIN 3+ lesions were 67.9 and 91.2%, respectively after adjusting for verification bias. Specificity for the same disease outcome and verification bias correction was 93.2% for VIA and 96.9% for HC II. Triaging of VIA positive women with HPV test would have considerably improved the positive predictive value (4.0 to 37.5% to detect CIN 3+) without significant drop in sensitivity. All VIA positive women and 74.0% of HC II positive women had colposcopy. There was high compliance to treatment and significant stage-shift of the screen-detected cancers towards more early stage.

The Singapore Cancer Registry has provided comprehensive population-based incidence data since 1968. This paper describes the population-based survival analysis of the registry data. All invasive primary cancers diagnosed from January 1, 1968 to December 31, 1992 were passively followed up until December 31, 1997. Only 5.8% were lost to follow-up. Cumulative and observed survival rates were calculated using Hakulinen's method. Overall 5-year relative survival rates have increased dramatically over the 25-year period in both genders. Significant increases are seen with nasopharynx, stomach and colo-rectum cancers, non-Hodgkin's lymphoma, leukemias and cancers of the testis, cervix, ovaries and breast. When compared with the Surveillance, Epidemiology and End Results (SEER) rates in the United States, the 5-year relative survival rates in Singapore are generally lower. However, the rate of change between the two countries is fairly similar. On the average, the rates are 10 to 15 years behind the SEER rates and 5 to 10 years behind Finland, Switzerland and Japan, but they are close to the UK rates. The age-standardized 5-year survival rate for Singapore is higher for most sites compared with other developing countries like Qidong (China), Madras (India), Bombay (India) and Chiang Mai (Thailand). The 25-year trend in cancer survival in Singapore showed two extreme groups: those showing no change and those showing significant improvements. Reducing the incidence of cancers belonging to the first group remains the only viable mode of cancer control. For cancers in the second group, improvement in survival is due to a combination of successful early detection measures and effective treatment services in Singapore.

Anthony B. MILLER*, Saloney NAZEER, Sharon FONN, Assia BRANDUP-LUKANOW, Rakshanda REHMAN, Hennie CRONJE, Rengaswamy SANKARANARAYANAN, Valentin KOROLTCHOUK, Kari SYRJANEN, Albert SINGER and Mathias ONSRUD on behalf of the participants Division of Clinical Epidemiology, German Cancer Research Center, Heidelberg, Germany Department of Gynecology and Obstetrics, Hopitaux Universitaires de Geneve, Geneva, Switzerland Women’s Health Project, Johannesburg, South Africa WHO Regional Office for European Region, Copenhagen, Denmark Department of Gynecology and Obstetrics, Fatimah Jinnah Medical College, Lahore, Pakistan Department of Obstetrics and Gynecology, The University of the Orange Free State, Bloemfontein, South Africa Unit of Descriptive Epidemiology, International Agency for Research on Cancer, Lyon, France Geneva, Switzerland Department of Pathology, Central Hospital, Kuopio, Finland Department of Women’s and Children’s Health, The Whittington Hospital, London, England Department of Gynecology and Obstetrics, University Hospital of Trondheim, Norway

A total of 3784 women aged 35 and above living in 26 villages in rural Maharashtra state, India, were invited to undergo a pelvic examination, to evaluate the performance of unaided visual inspection by trained paramedical workers in detecting cervical cancer. Of this number, 2135 (56.4%) women complied with the invitation. Paramedical workers scored 1120 (57.3%) and 1 18 (6%) women as having abnormal cervices using the lowand high-threshold criteria respectively. There was good agreement between the visual findings of the paramedical workers and those of a gynaecologist. All subjects had a cervical smear. A total of 10 cervical cancers were detected by cytology/histology. The sensitivity of visual inspection by paramedical workers to detect cervical cancer was 90.0% using the low threshold and 60.0% with the high threshold to define a positive test. The values for specificity were 42.8% and 94.5% respectively. The results obtained by the gynaecologist were very similar. Cost savings implied by limiting cytology/other investigations to approximately half of the population pre-selected on the basis of visual inspection are likely to be offset by the necessity to repeat the test at frequent intervals, repeated follow-up visits and other investigations. © 1996 Wiley-Liss, Inc.

Population prevalence of human papillomavirus (HPV) and cervical intraepithelial neoplasias (CIN) is an important indicator to judge the disease burden in the community, to monitor the performance of cervical cancer screening program and to assess the impact of HPV vaccination program. India being a country without any cervical cancer screening program has no published data on the population prevalence of CIN and only a few large community-based studies to report the high-risk HPV prevalence. The objective of our study was to study HPV and CIN prevalence in a previously unscreened population. We pooled together the results of three research studies originally designed to assess the performance of visual inspection after acetic acid application and Hybrid Capture 2 (HC 2). Nearly 60% of the screened women had colposcopy irrespective of their screening test results. The diagnosis and grading of cervical neoplasias were based on histology. The age standardized prevalence of HPV by HC 2 test was 6.0%. Age-adjusted prevalence of CIN1 and CIN2 was 2.3% and 0.5%, respectively. The age-adjusted prevalence of CIN3 was 0.4% and that of invasive cancer was 0.2%. The prevalence of high-risk HPV was relatively low in the population we studied, which is reflected in the low prevalence of high-grade CIN. The prevalence of CIN3 remained constant across age groups due to absence of screening.

Most developed countries insist on the prevention of colorectal cancer (CRC) and offer screening to the population. Mass screening is proposed to both sexes in the population aged 50 years or more. Colonoscopy is then offered to persons having a positive faecal occult blood test. This recommendation should not be diffused over the world without considering the distinct dimensions of the risk and resources in developed and developing countries. A national screening policy is legitimate in developed countries like Japan, South Korea, and in North America and Europe. On the other hand, a mass screening policy for CRC is not recommended in most developing countries. The limited amount of resources attributed to health care for cancer should concern other indications in the control of common cancers, particularly in the cervix or liver. Indeed the risk of CRC is very low in most regions of Africa, and in some countries of South America and Asia.

A case-control study of oesophageal cancer was carried out in Trivandrum, Kerala, involving 267 cases and 895 controls. Risk factors studied in males were pan (betel)-tobacco chewing, bidi and cigarette smoking, drinking alcohol and taking snuff. Only pan-tobacco chewing was investigated in females as very few indulged in the other habits. Among males significant associations with higher risk were observed for bidi smoking (p less than 0.001), bidi plus cigarette smoking (p greater than 0.05) and drinking alcohol (p less than 0.001). While a significant effect of duration of pan-tobacco chewing (p less than 0.005) was observed in males, there was no significant trend, the risk first falling then rising as duration of use increased. This was partly due to confounding with smoking. No effect of pan-tobacco use was observed in females. A step-wise model was fitted, retaining only those risk factors which were significant when adjusted for other factors; the risk factors included were duration of pan-tobacco chewing, duration of bidi smoking, daily frequency of bidi and cigarette smoking and alcohol use (yes or no). An adjusted relative risk of 2.03 was observed for a pan-tobacco habit of more than 40 years' duration, of 4.70 for more than 20 years of bidi smoking, of 4.80 for more than 20 bidis/cigarettes per day, and of 2.33 for regular alcohol use (in each category relative to a baseline of those never indulging in the relevant habit).

A case-control study of cancer of the larynx was carried out in Kerala, Southern India, on 191 male cancer cases and 549 male hospital-based controls. Risk factors investigated were pan(betel)-tobacco chewing, bidi and cigarette smoking, drinking alcohol and inhaling snuff. Significant positive associations with risk were observed for bidi smoking (p less than 0.001), bidi and cigarette smoking (p less than 0.001) and drinking alcohol (p less than 0.001). A predisposing effect of smoking cigarettes alone approached significance (0.1 less than p less than 0.05). What appeared to be an almost significant protective effect of pan-tobacco chewing (0.1 less than p less than 0.05) was found to be an artefact of confounding with smoking, and indeed a significant predisposing effect was observed of occasional chewing (p less than 0.001). After a stepwise logistic regression to eliminate those factors which were not significant when adjusted for other factors, significant effects remained of durations of bidi smoking and cigarette smoking, daily frequency of bidi and cigarette smoking and duration of alcohol drinking. Relative risks of 7.12, 5.18 and 2.58 were observed for durations of more than 20 years of bidi smoking, cigarette smoking and drinking alcohol respectively, and a relative risk of 12.68 was observed for those smoking more than 20 bidis/cigarettes per day, in each case relative to a baseline of those negative for the relevant habit.

The impact of screening by visual inspection with acetic acid (VIA), cytology or HPV testing on cervical cancer incidence and mortality is investigated in a cluster randomized controlled trial in India. We report findings after the screening phase, when 52 clusters, with a total of 142,701 women aged 30-59 years in Osmanabad District, India, were randomized into 4 arms for a single round of screening by trained midwives with either VIA, cytology or HPV testing as well as a control group. All laboratory tests were done locally. Test-positive women underwent investigations (colposcopy/biopsy) and treatment in the base hospital. Data on participation, test positivity, positive predictive value and detection rates of cervical neoplasia were analyzed using cluster design methodology. Of the eligible women, 72-74% were screened. Test positivity rates were 14.0% for VIA, 7.0% for cytology and 10.3% for HPV. The detection rate of high-grade lesions was similar in all intervention arms (0.7% for VIA, 1.0% for cytology and 0.9% for HPV testing) (p = 0.06, Mann-Whitney test). While the detection rate for VIA dropped to 0.5% with declining test positivity during the course of the study, it remained constant for cytology and HPV testing. Over 85% of women with high-grade lesions received treatment. Our results show that a high level of participation and good-quality cytology can be achieved in low-resource settings. VIA is a useful alternative but requires careful monitoring. Detection rates obtained by HPV testing were similar to cytology, despite higher investments.

The impact of a single round of screening of visual inspection with acetic acid (VIA) on cervical cancer incidence and mortality was investigated in a cluster randomized trial in south India. Women 30-59 years of age in 113 clusters in Dindigul District were randomized to VIA screening (57 clusters, 48,225 women) by nurses and to a control group (56 clusters, 30,167 women). 30,577 eligible women were screened between May 2000 and April 2003; 2,939 (9.6%) screen-positive women were investigated with colposcopy by nurses and 2,777 (9.1%) women had biopsy. CIN 1 was diagnosed in 1,778 women, CIN 2-3 lesions were found in 222, and there were 69 screen detected invasive cervical cancers. The detection rates of lesions per 1,000 screened women were 58.2 for CIN 1, 7.3 for CIN 2-3, and 2.3 for invasive cancer. The detection rate of high-grade lesions in our study was 2-3-fold higher than those observed in repeatedly screened populations in developed countries. 71% of women with CIN 1 and 80% of those with CIN 2-3 lesions accepted cryotherapy provided by nurses and surgical treatment by mid-level clinicians. Overall, 97 and 34 incident cervical cancer cases were observed in the intervention and control arms, respectively. The intervention arm accrued 124,144 person years and the control arm accrued 90,172 during the study period. The age standardized cervical cancer incidence rates were 92.4/100,000 person-years in the intervention and 43.1/100,000 in the control arms. In the screened arm, 35.0% of cases were in Stage I as opposed to none in the control arm. The preliminary findings from our study indicate that not only is a VIA-based screening programme feasible, safe and acceptable to a population in rural settings, it also results in early detection of cervical neoplasia.

Oral leukoplakia, oral submucous fibrosis and erythroplakia are 3 major types of oral premalignant lesions. Multiple oral premalignant lesions may possibly develop due to field cancerization, where carcinogenic exposures can cause simultaneous genetic defects to the upper aerodigestive tract epithelium, putting the epithelium at high risk for development of premalignant lesions at different stages of carcinogenesis. There have been no epidemiological studies on risk or protective factors of the disease. A case-control study was conducted with data from the baseline screening of a randomized oral cancer screening trial in Kerala, India. A total of 115 subjects with multiple oral premalignant lesions (8–10% of oral premalignant lesions in our case series) were included: 64 subjects with oral leukoplakia and oral submucous fibrosis, 19 subjects with oral leukoplakia and erythroplakia, 22 subjects with oral submucous fibrosis and erythroplakia and 10 subjects with all 3 lesions. Individuals without oral lesions were considered controls (n=47,773). The odds ratio (OR) for ever tobacco chewers was 37.8 (95% confidence interval (CI)=16.2–88.1) when adjusted for age, sex, education, BMI, smoking, drinking and fruit/vegetable intake. Dose-response relationships were seen for the frequency (p

Unaided visual inspection or “downstaging” has been suggested as a potential alternative method for cervical cancer screening in developing countries. Our study was designed to evaluate the accuracy of downstaging to detect cervical neoplasia in a low-resource setting. A total of 6,399 women aged 30–64 years were screened with downstaging by trained nonmedical health workers. Two thresholds were used to define positive downstaging: “low threshold” when any visible abnormality on the cervix was considered positive and “high threshold” when selected abnormalities such as bleeding on touch, bleeding erosion, hypertrophied oedematous cervix, congested stippled cervix and growth or ulcer constituted the positive test. All women underwent a colposcopy examination. Biopsies were directed when colposcopy revealed abnormal lesions. True disease status was defined as histologically proven moderate dysplasia and worse lesions. Since all the participants received a diagnostic (reference) investigation (biopsy and/or colposcopy), sensitivity, specificity and predictive values were estimated directly. Low- and high-threshold downstaging were positive in 1,585 (24.8%) and 460 (7.2%) women, respectively. The sensitivities of low- and high-threshold downstaging to detect high-grade precursors and invasive cancers were 48.9% and 31.9%, respectively. The specificities were 75.8% and 93.3%, respectively. These results indicate that downstaging is not suitable as an independent primary screening modality for cervical neoplasia. © 2002 Wiley-Liss, Inc.

Between 1996 and 1999 we carried out a case-control study in 3 areas in Southern India (Bangalore, Madras and Trivandrum) including 591 incident cases of cancer of the oral cavity (282 women) and 582 hospital controls (290 women), frequency-matched with cases by age and gender. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from unconditional multiple logistic regressions and adjusted for age, gender, center, education, chewing habit and (men only) smoking and drinking habits. Low educational attainment, occupation as a farmer or manual worker and various indicators of poor oral hygiene were associated with significantly increased risk. An OR of 2.5 (95% CI 1.4-4.4) was found in men for smokingor = 20 bidi or equivalents versus 0/day. The OR for alcohol drinking was 2.2 (95% CI 1.4-3.3). The OR for paan chewing was more elevated among women (OR 42; 95% CI 24-76) than among men (OR 5.1; 95% CI 3.4-7.8). A similar OR was found among chewers of paan with (OR 6.1 in men and 46 in women) and without tobacco (OR 4.2 in men and 16.4 in women). Among men, 35% of oral cancer is attributable to the combination of smoking and alcohol drinking and 49% to pan-tobacco chewing. Among women, chewing and poor oral hygiene explained 95% of oral cancer.

Although tobacco habits have been associated with the risk of oral leukoplakia, alcohol drinking and body mass index (BMI) as risk factors have not been well established. The purpose of this study is to evaluate the independent effects of drinking, BMI, tobacco chewing and smoking on the risk of oral leukoplakia. A case-control study was conducted, with data from an ongoing randomized oral cancer screening trial in Kerala, India. Trained health workers conducted interviews and performed oral visual inspections to identify oral premalignant lesions such as leukoplakia. The logistic regression model in SAS was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). A total of 927 leukoplakia cases and 47,773 controls were included in the analysis. Ever alcohol drinking was a significant risk factor for oral leukoplakia among nonsmokers (OR=2.1, 95%CI=1.3, 3.4) and non-chewers (OR=1.8, 95%CI=1. 3, 2.5) after adjusting for age, sex, education, BMI and tobacco habits. The association with alcohol drinking was stronger among women (OR=3.9, 95%CI=1.5, 10.4) than men (OR=1.5, 95%CI=1.3, 1.9). An inverse dose-response relationship was observed between BMI and the risk of oral leukoplakia (p for trend=0.0075). Tobacco chewing was a stronger risk factor for women (OR=37.7, 95%CI=24.2, 58.7) than for men (OR=3.4, 95%CI=2.8, 4.1). Smoking was a slightly stronger risk factor for men (OR=3.3, 95%CI=2.5, 4.3) than for women (OR=2.0, 95%CI=1.5, 2.9). In conclusion, alcohol drinking was found to be an independent risk factor while BMI might be inversely associated with the risk of oral leukoplakia in an Indian population.

No cancer incidence data from Pakistan have been published in the 5 decades since independence. Incidence data for the period 1995-1997 from the population of the Karachi South district (1.7 million) are presented here. A total of 4,268 new cancer cases were registered during this period: 2,160 cases in males and 2,108 cases in females. Overall, 95.3% of the incident cases were microscopically verified. The incidence rates for all cancers combined were 80.5 per 100,000 (crude) and 136.7 per 100,000 (age- standardised rates [ASR]) for males and 91.8 (crude) and 163.2 per 100,000 (ASR) for females. In males, lung cancer (ASR 20.3) was the most frequently recorded malignancy followed by oral cavity (ASR 13.8) and larynx cancer (ASR 8.6). In females, breast was the most common site of cancer, accounting for one third of female cancers (ASR 51.7), followed by oral cavity (ASR 14.1) and ovarian cancer (ASR 10.2). Karachi reports the highest incidence of breast cancer for any Asian population, except Jews in Israel. Tobacco smoking is estimated to be responsible for 40% of cancers in males and tobacco chewing for a further substantial proportion of head and neck cancers.

Thailand is one of the few developing countries for which population-based cancer survival data are available. Using clinical follow-up information and reply-paid postal enquiries, 10,333 residents of Khon Kaen province registered with cancer in the period 1985-1992 were followed-up to the end of 1993. The sites of the most common cancers in the province were liver (5-year relative survival rate 9.2%), cervix (60.1%), lung (15.4%), breast (48.1%) and large bowel (41.9%). Results for Khon Kaen were compared with age-standardized survival data for the US and Scotland. Survival was consistently higher for US whites compared to Khon Kaen residents for those cancers whose prognosis is associated with early diagnosis (breast, cervix and large bowel) or the availability of intensive therapy (leukaemia and lymphoma). The main implication of these results for cancer control in Thailand is that the interventions of greatest potential benefit are those designed to promote early detection. More than one-third of all cancers in Thailand are liver tumours: primary prevention through control of hepatitis-B infection and liver fluke infestation is the only effective strategy for their control.

Survival from cancer reflects the aggressiveness of the disease, the effectiveness of treatment and host factors such as age. While hospital-based survival rates are typically used to evaluate the care provided in a particular hospital, population-based survival reflects the effectiveness of the overall cancer control strategy in the region. Here, we report the survival experience of 1514 breast cancer patients registered by the Bangalore population-based registry during 1982-1989. There have been very few reports on survival from cancer in India, mainly because of poor patient follow-up and inadequate system of registration of death. This has been largely overcome in this study by means of active follow-up through visits of homes of patients. Scrutiny of medical records and matching with death certificates, was also carried out in a small proportion (12%) of cases. Thus, information on vital status (whether dead or alive) as on January 1, 1993 was available for 1334 (88%) subjects and partial follow up data were available for a further 34 (2%). The observed 5 year survival was 42.3% and the corresponding relative survival was 46.8%. The observed survival was 57.4% for localized disease, 45.8% for direct extension, 37% for those with regional node involvement, 14.2% for distant metastasis and 38.3% for those with unstaged disease. The clinical extent of disease and the educational status were independent predictors of survival.

A case-control study of cancer of the oral tongue and floor of mouth was conducted in Kerala, Southern India, on 228 cases and 453 hospital-based controls, matched for age, sex and religion. We studied pan(betel)-tobacco-chewing, bidi (local type of cigarette)-and-cigarette-smoking, alcohol-drinking and snuff use, for their associations with risk, in males. Among females, only pan-tobacco-chewing was analyzed, as very few females indulged in the other habits. In males, a significantly increased risk was observed in association with pan-tobacco-chewing, bidi-smoking, bidi-plus-cigarette-smoking (but not cigarette-smoking alone) and alcohol-drinking (p less than 0.001 in all cases), although the effect of alcohol was no longer significant when adjusted for the other significant predisposing factors. Among females, pan-tobacco-chewing had a similar predisposing effect to that observed in males (p less than 0.001). In males an adjusted relative risk of 6.14 was associated with chewing 10 or more pan-tobacco quids per day (relative to those who never chewed). The corresponding relative risk in females was 9.27. In males, an adjusted relative risk of 7.46 was observed for those smoking 20 or more bidis per day (relative to never-smokers).