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Verbal-autopsy-based projection of cancer deaths in IndiaComplete information about causes of deaths is valuable for planning and implementation of eff ective public health services. However, a civil registration system (CRS) of deaths is far from complete in many countries, including India. Only half the estimated 9·8 million deaths annually are captured by the CRS and fewer than 4% are medically certifi ed in India, where more than three-quarters of deaths occur at home.1 The Sample Registration System (SRS) has become an

alternative method to generate reliable data for births and deaths. The SRS has 4433 rural and 3164 urban census units that cover 7·2 million people in 1·5 million households, and register about 50 000 deaths annually.2

In The Lancet, Rajesh Dikshit and colleagues3 estimate the cancer mortality rate in India for 2010, using age-specifi c and sex-specifi c cancer deaths based on a physician’s review of SRS verbal autopsy fi ndings during 2001–03.3 They project cancer mortality rates for all

in pregnancy maintenance, and ought to prompt basic and translational studies to investigate these mechanisms.

Perhaps a fi rst step in improving our understanding of the problem of cervical incompetence or insuffi ciency is to stop using pejorative, confusing, and imprecise terms (such as incompetence or insuffi ciency) that are anachronistic and ill-defi ned biologically. A term such as precocious cervical ripening might be more appropriate in view of the current understanding.

Slow progress in tackling the intractable nature of preterm birth is the result of diffi culty in undertaking a clinical trial in this population. Hypothesis testing requires an adequate sample size and precocious cervical ripening is uncommon. As shown in the study by Goya and colleagues, only 6% of women had a cervical length that met trial entry criteria. The study population represented only 3% of women screened, making this screening approach fairly ineffi cient. The public health and policy implications, and the generalisability of the fi ndings in studies such as that by Goya and colleagues are aff ected by these diffi culties.

Additional clarity might be brought to bear on prevention of preterm birth by focusing basic research on elucidation of the biological processes that are responsive to those interventions that have proven to be eff ective. Since cerclage and possibly pessary use seem eff ective in treating this disorder, one must consider that mechanical factors are at least a contributor to the process of cervical shortening. Similarly, the eff ectiveness of vaginal progesterone suggests that biochemical processes are key because progesterone can aff ect cervical matrix metalloproteinases, prosta glandins, and cytokines, molecules that can aff ect cervical structure.

Strict criteria must be applied before acceptance of fi ndings from clinical trials, because the eff ect of bias is serious. The fi ndings of a recent Cochrane systematic review did not identify a single published study about pessary use for preterm birth prevention that met criteria for acceptance.8 The study by Goya and colleagues is a fi rst step toward addressing this defi ciency, although the higher than expected rate of preterm birth (27%) in those women not receiving a pessary may be indicative of potential bias in the study. Additional well designed studies are needed before pessary use can be validated as an eff ective treatment for women with precocious cervical ripening.

*Steve N Caritis, Hyagriv SimhanMagee Womens Hospital, Pittsburgh, PA 15213, USAscaritis@mail.magee.edu

We declare that we have no confl icts of interest.

1 Goya M, Pratcorona L, Merced C, et al, on behalf of the Pesario Cervical para Evitar Prematuridad (PECEP) Trial Group. Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial. Lancet 2012; published online April 2, 2012. DOI:10.1016/S0140-6736(12)60030-0.

2 Harger JH. Cerclage and cervical insuffi ciency: an evidence-based analysis. Obstet Gynecol 2001; 100: 1313–27.

3 Owen J, Hankins, G, Iams JD, et al. Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length. Am J Obstet Gynecol 2009; 201: 375.e1–8.

4 Berghella V, Bega G, Tolosa JE, Berghella M. Ultrasound assessment of the cervix. Clin Obstet Gynecol 2003; 46: 947–62.

5 Dharan VB, Ludmir J. Alternative treatment for a short cervix: the cervical pessary. Semin Perinatol 2009; 33: 338–42.

6 Berghella V, Rafael TJ, Szychowski JM, Rust OA, Owen J. Cerclage for short cervix on ultrasonography in women with singleton gestations and previous preterm birth. Obstet Gynecol 2011; 117: 663–71.

7 Hassan SS, Romero R, Vidyadhari D, et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol 2011; 38: 18–31.

8 Abdel-Aleem H, Shaaban OM, Abdel-Aleem MA. Cervical pessary for preventing preterm birth. Cochrane Database Syst Rev 2010; 8: CD007873.

Published OnlineMarch 28, 2012

DOI:10.1016/S0140-6736(12)60467-X

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ages and for major cancers in people aged 30–69 years by sex, place of residence, religion, education, and state in India, based on a nationally representative sample of households. Although reliable cancer incidence data have been reported by population cancer registries in some regions of India,4,5 existing cancer mortality data seem to be incomplete as assessed by matching with CRS records. Dikshit and colleagues’ landmark study,3 based on a nationally representative sample with adequate coverage of rural areas, provides more complete and comprehensive cancer mortality data for India; it represents notable progress in obtaining direct estimates of the cancer burden, particularly in regions that are not covered by cancer registration.

Although verbal autopsy fi ndings are increasingly being used to assess cause-specifi c mortality in popu-lations without a CRS, cause-of-death inferences and comparability of results might be challenging because of the diff ering views of local physicians and misclassifi cation of the causes of deaths, particularly in old people. For cancer deaths, assigning causes of death to internal cancers such as stomach, liver, bowel, and kidney can be more challenging than for sites such as head and neck, breast, and cervix. The inclusion of a small number of in-situ and benign tumours and more stomach cancer deaths than incident cases in the registry regions probably indicates physicians’ uncertainty in assigning causes of death in this study. Despite these concerns, this study is a valuable exercise in improving cancer mortality data in India and has important implications since estimates from China and India con tri-bute substantially to the global burden of disease.

Although total deaths and age-specifi c and sex-specifi c cancer mortality rates in India have been previously estimated by the International Agency for Research on Cancer (IARC),6 analysis by religion, education, and state is Dikshit and colleagues’ focus. The estimate of 556 400 all-cancer deaths for 2010 is lower than the 633 500 deaths estimated by IARC for 2008,6 based on cancer incidence4 and 5-year survival rates from selected cancer registries in India.7 The lower estimates could partly refl ect the diff ering data sources and methods used, but they might also indicate misclassifi cation of cause of death in old people, discrepancies in the interpretation of fi ndings from verbal autopsies, and adequate representation of rural areas (where cancer incidence is lower than

in urban areas) in the SRS.4 However, estimates based on existing cancer registries, which cover many more urban areas and cities5 than smaller towns and villages, might overestimate cancer mortality.

About 71% of all cancer deaths occurred in individuals aged 30–69 years, emphasising the substantial social and economic gains that would be associated with a successful cancer prevention programme. Among men aged 30–69 years, the most common causes of cancer death were oral and pharyngeal, stomach, and lung cancers, accounting for 46·9% of cancer deaths. Among women, 51·2% of cancer deaths were caused by cervix, stomach, breast, and oral and pharyngeal cancers. Tobacco-related and infection-related cancers contributed to substantial proportions of cancer deaths in both sexes. Thus, interventions such as tobacco control, vaccination against human papillomavirus and hepatitis B, cervical cancer screening,8,9 and early detection and treatment of oral10 and breast cancers11,12 would have a substantial eff ect on the prevention of cancer deaths.

The similar mortality rates in urban and rural areas3 is surprising, although the higher mortality to incidence ratio in rural areas, documented by Indian registries, might be due to a mix of late presentation, poor socioeconomic status, and restricted access to cancer services in rural areas.4,5 The higher mortality rates in poorly educated people are consistent with previous studies,13 providing a boost for public education campaigners by adding an important theme about spreading cancer awareness. There was a more than four-times diff erence in cancer mortality rates in men and

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Misoprostol for all women seeking abortion?Abortion is one of the central pillars of safe maternal and women’s health. Legal induced abortion is a very safe procedure—deaths are rare and fewer than after birth.1 The major health concern is restricted access to services, but abortion methods also require improvement. Medical (drug-induced) abortion has done much to improve availability, although cost remains an issue. In many situations worldwide, sur gically induced abortion is the only method available and, in this respect, Olav Meirik and colleagues’ study2 in The Lancet is important.

For three decades, cervical preparation before sur-gical abortion has been known to reduce the risk of complications. An open, soft cervix facilitates entry to the uterine cavity, which makes the abortion procedure easier for patient and surgeon than if the cervix is fi rm. In a large retrospective series,3 the use of laminaria before surgery

was associated with reduced uterine perforation and signifi cantly reduced cervical injury,4 and these eff ects were enhanced when the abortion was done by a skilled practitioner. Rapidly acting osmotic dilators are available, but pharmaceutical approaches, includ ing prostaglandin analogues and antiprogesterones, have also been developed.5 Although mifepristone is very eff ective, it is expensive and needs a delay of 24 h for good eff ect.6 Of the prostaglandin analogues, misoprostol has become prominent for both surgical and medical abortion,7 because it is eff ective, easy to use, and cheap. Many studies5 have shown the eff ectiveness of misoprostol given vaginally, sublingually, or orally 3 h before surgery. However, none of these studies has been large enough to show a reduction in serious complications, and caution prevents recommendations for routine use.

a more than two-times diff erence in women between states in India, with lower rates in poor states. The highest mortality rates were reported for northeastern states where incidence rates were also the highest.4 Although the diff erences between some states seem to be striking (eg, Kerala and Tamil Nadu; Gujarat and Maharashtra for men), the results could be a benchmark for states without cancer registration systems. The fi ndings from this important study should encourage explorations of methodological diff erences in providing national estimates in India. Further investigations should also be initiated to unravel factors contributing to the striking variations in cancer rates, to provide further interventions to reduce the cancer burden in India, and to stimulate the eventual implementation of a complete CRS of deaths based on systematic medical certifi cation so that verbal-autopsy-based projections would no longer be needed.

*Rengaswamy Sankaranarayanan, Rajaraman SwaminathanScreening Group, International Agency for Research on Cancer, 69008 Lyon, France (RSa); and Department of Biostatistics and Cancer Registry, Cancer Institute (WIA), Chennai, India (RSw)sankarr@iarc.fr

We declare that we have no confl icts of interest.

1 Mahal A, Karan A, Engelgau M. The economic implications of non-communicable disease for India. Washington, DC: International Bank for Reconstruction and Development and World Bank, 2010. http://sitesresources.worldbank.org/HEALTHNUTRITIONANDPOPULATION/Resources/281627-1095698140167/EconomicImplicationsofNCDforIndia.pdf (accessed March 9, 2012).

2 Offi ce of the Registrar General India, Ministry of Home Aff airs. Sample Registration System. SRS Bulletin 2011; 45: 1–7.

3 Dikshit R, Gupta PC, Ramasundarahettige C, et al, for the Million Death Study Collaborators. Cancer mortality in India: a nationally representative survey. Lancet 2012; published online March 28. DOI:10.1016/S0140-6736(12)60358-4.

4 National Cancer Registry Programme. Three year report of population based cancer registries 2006–2008: incidence and distribution of cancer (fi rst report of 20 PBCRs in India). Bangalore: Indian Council of Medical Research, 2010.

5 Swaminathan R, Selvakumaran R, Esmy PO, et al. Cancer pattern and survival in a rural district in South India. Cancer Epidemiol 2009; 33: 325–31.

6 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN v1.2 Cancer incidence and mortality worldwide. IARC CancerBase number 10. Lyon: International Agency for Research on Cancer, 2010. http://globocan.iarc.fr (accessed March 9, 2012).

7 Sankaranarayanan R, Swaminathan R. Cancer survival in Africa, Asia, the Caribbean and Central America (SurvCan). IARC Scientifi c Publications number 162. Lyon: International Agency for Research on Cancer, 2011.

8 Sankaranarayanan R, Nene BM, Shastri SS, et al. HPV screening for cervical cancer in rural India. N Engl J Med 2009; 360: 1385–94.

9 Sankaranarayanan R, Esmy PO, Rajkumar R, et al. Eff ect of visual screening on cervical cancer incidence and mortality in Tamil Nadu, India: a cluster-randomised trial. Lancet 2007; 370: 398–406.

10 Sankaranarayanan R, Ramadas K, Thomas G, et al, for the Trivandrum Oral Cancer Screening Study Group. Eff ect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial. Lancet 2005; 365: 1927–33.

11 Sankaranarayanan R, Ramadas K, Thara S, et al. Clinical breast examination: preliminary results from a cluster randomized controlled trial in India. J Natl Cancer Inst 2011; 103: 1476–80.

12 Mittra I, Mishra JA, Singh S, et al. A cluster randomized, controlled trial of breast and cervix cancer screening in Mumbai, India: methodology and interim results after three rounds of screening. Int J Cancer 2010; 126: 976–84.

13 Nandakumar A, Anantha N, Venugopal TC, Sankaranarayanan R, Thimmasetty K, Dhar M. Survival in breast cancer: a population-based study in Bangalore, India. Int J Cancer 1995; 60: 593–96.

Published OnlineMarch 8, 2012

DOI:10.1016/S0140-6736(12)60037-3

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