Bhagwan M. Nene

BACKGROUND: In October 1999, we began to measure the effect of a single round of screening by testing for human papillomavirus (HPV), cytologic testing, or visual inspection of the cervix with acetic acid (VIA) on the incidence of cervical cancer and the associated rates of death in the Osmanabad district in India. METHODS: In this cluster-randomized trial, 52 clusters of villages, with a total of 131,746 healthy women between the ages of 30 and 59 years, were randomly assigned to four groups of 13 clusters each. The groups were randomly assigned to undergo screening by HPV testing (34,126 women), cytologic testing (32,058), or VIA (34,074) or to receive standard care (31,488, control group). Women who had positive results on screening underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment. RESULTS: In the HPV-testing group, cervical cancer was diagnosed in 127 subjects (of whom 39 had stage II or higher), as compared with 118 subjects (of whom 82 had advanced disease) in the control group (hazard ratio for the detection of advanced cancer in the HPV-testing group, 0.47; 95% confidence interval [CI], 0.32 to 0.69). There were 34 deaths from cancer in the HPV-testing group, as compared with 64 in the control group (hazard ratio, 0.52; 95% CI, 0.33 to 0.83). No significant reductions in the numbers of advanced cancers or deaths were observed in the cytologic-testing group or in the VIA group, as compared with the control group. Mild adverse events were reported in 0.1% of screened women. CONCLUSIONS: In a low-resource setting, a single round of HPV testing was associated with a significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer.

BACKGROUND: Previous efforts to report estimates of cancer incidence and mortality in India and its different parts include the National Cancer Registry Programme Reports, Sample Registration System cause of death findings, Cancer Incidence in Five Continents Series, and GLOBOCAN. We present a comprehensive picture of the patterns and time trends of the burden of total cancer and specific cancer types in each state of India estimated as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 because such a systematic compilation is not readily available. METHODS: We used all accessible data from multiple sources, including 42 population-based cancer registries and the nationwide Sample Registration System of India, to estimate the incidence of 28 types of cancer in every state of India from 1990 to 2016 and the deaths and disability-adjusted life-years (DALYs) caused by them, as part of GBD 2016. We present incidence, DALYs, and death rates for all cancers together, and the trends of all types of cancers, highlighting the heterogeneity in the burden of specific types of cancers across the states of India. We also present the contribution of major risk factors to cancer DALYs in India. FINDINGS: 8·3% (95% uncertainty interval [UI] 7·9-8·6) of the total deaths and 5·0% (4·6-5·5) of the total DALYs in India in 2016 were due to cancer, which was double the contribution of cancer in 1990. However, the age-standardised incidence rate of cancer did not change substantially during this period. The age-standardised cancer DALY rate had a 2·6 times variation across the states of India in 2016. The ten cancers responsible for the highest proportion of cancer DALYs in India in 2016 were stomach (9·0% of the total cancer DALYs), breast (8·2%), lung (7·5%), lip and oral cavity (7·2%), pharynx other than nasopharynx (6·8%), colon and rectum (5·8%), leukaemia (5·2%), cervical (5·2%), oesophageal (4·3%), and brain and nervous system (3·5%) cancer. Among these cancers, the age-standardised incidence rate of breast cancer increased significantly by 40·7% (95% UI 7·0-85·6) from 1990 to 2016, whereas it decreased for stomach (39·7%; 34·3-44·0), lip and oral cavity (6·4%; 0·4-18·6), cervical (39·7%; 26·5-57·3), and oesophageal cancer (31·2%; 27·9-34·9), and leukaemia (16·1%; 4·3-24·2). We found substantial inter-state heterogeneity in the age-standardised incidence rate of the different types of cancers in 2016, with a 3·3 times to 11·6 times variation for the four most frequent cancers (lip and oral, breast, lung, and stomach). Tobacco use was the leading risk factor for cancers in India to which the highest proportion (10·9%) of cancer DALYs could be attributed in 2016. INTERPRETATION: The substantial heterogeneity in the state-level incidence rate and health loss trends of the different types of cancer in India over this 26-year period should be taken into account to strengthen infrastructure and human resources for cancer prevention and control at both the national and state levels. These efforts should focus on the ten cancers contributing the highest DALYs in India, including cancers of the stomach, lung, pharynx other than nasopharynx, colon and rectum, leukaemia, oesophageal, and brain and nervous system, in addition to breast, lip and oral cavity, and cervical cancer, which are currently the focus of screening and early detection programmes. FUNDING: Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India.

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.