in pregnancy maintenance, and ought to prompt basic and translational studies to investigate these mechanisms. Perhaps a ﬁrst step in improving our understanding of the problem of cervical incompetence or insuﬃciency is to stop using pejorative, confusing, and imprecise terms (such as incompetence or insuﬃciency) that are anachronistic and ill-deﬁned 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 diﬃculty 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 ineﬃcient. The public health and policy implications, and the generalisability of the ﬁndings in studies such as that by Goya and colleagues are aﬀected by these diﬃculties. 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 eﬀective. Since cerclage and possibly pessary use seem eﬀective in treating this disorder, one must consider that mechanical factors are at least a contributor to the process of cervical shortening. Similarly, the eﬀectiveness of vaginal progesterone suggests that biochemical processes are key because progesterone can aﬀect cervical matrix metalloproteinases, prostaglandins, and cytokines, molecules that can aﬀect cervical structure.
Strict criteria must be applied before acceptance of ﬁndings from clinical trials, because the eﬀect of bias is serious. The ﬁndings 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 ﬁrst step toward addressing this deﬁciency, 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 eﬀective treatment for women with precocious cervical ripening. *Steve N Caritis, Hyagriv Simhan Magee Womens Hospital, Pittsburgh, PA 15213, USA firstname.lastname@example.org We declare that we have no conﬂicts of interest. 1
4 5 6
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/S01406736(12)60030-0. Harger JH. Cerclage and cervical insuﬃciency: an evidence-based analysis. Obstet Gynecol 2001; 100: 1313–27. 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. Berghella V, Bega G, Tolosa JE, Berghella M. Ultrasound assessment of the cervix. Clin Obstet Gynecol 2003; 46: 947–62. Dharan VB, Ludmir J. Alternative treatment for a short cervix: the cervical pessary. Semin Perinatol 2009; 33: 338–42. 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. 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. Abdel-Aleem H, Shaaban OM, Abdel-Aleem MA. Cervical pessary for preventing preterm birth. Cochrane Database Syst Rev 2010; 8: CD007873.
Verbal-autopsy-based projection of cancer deaths in India Published Online March 28, 2012 DOI:10.1016/S01406736(12)60467-X See Articles page 1807
Complete information about causes of deaths is valuable for planning and implementation of eﬀective 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 certiﬁed 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 agespeciﬁc and sex-speciﬁc cancer deaths based on a physician’s review of SRS verbal autopsy ﬁndings during 2001–03.3 They project cancer mortality rates for all www.thelancet.com Vol 379 May 12, 2012
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 ﬁndings are increasingly being used to assess cause-speciﬁc mortality in populations without a CRS, cause-of-death inferences and comparability of results might be challenging because of the diﬀering views of local physicians and misclassiﬁcation 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 contribute substantially to the global burden of disease. Although total deaths and age-speciﬁc and sexspeciﬁc 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 reﬂect the diﬀering data sources and methods used, but they might also indicate misclassiﬁcation of cause of death in old people, discrepancies in the interpretation of ﬁndings from verbal autopsies, and adequate representation of rural areas (where cancer incidence is lower than www.thelancet.com Vol 379 May 12, 2012
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 eﬀect 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 fourtimes diﬀerence in cancer mortality rates in men and 1771
a more than two-times diﬀerence 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 diﬀerences 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 ﬁndings from this important study should encourage explorations of methodological diﬀerences 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 certiﬁcation so that verbalautopsy-based projections would no longer be needed.
*Rengaswamy Sankaranarayanan, Rajaraman Swaminathan
Screening Group, International Agency for Research on Cancer, 69008 Lyon, France (RSa); and Department of Biostatistics and Cancer Registry, Cancer Institute (WIA), Chennai, India (RSw) email@example.com We declare that we have no conﬂicts 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).
Oﬃce of the Registrar General India, Ministry of Home Aﬀairs. Sample Registration System. SRS Bulletin 2011; 45: 1–7. 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. National Cancer Registry Programme. Three year report of population based cancer registries 2006–2008: incidence and distribution of cancer (ﬁrst report of 20 PBCRs in India). Bangalore: Indian Council of Medical Research, 2010. 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. 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). Sankaranarayanan R, Swaminathan R. Cancer survival in Africa, Asia, the Caribbean and Central America (SurvCan). IARC Scientiﬁc Publications number 162. Lyon: International Agency for Research on Cancer, 2011. Sankaranarayanan R, Nene BM, Shastri SS, et al. HPV screening for cervical cancer in rural India. N Engl J Med 2009; 360: 1385–94. Sankaranarayanan R, Esmy PO, Rajkumar R, et al. Eﬀect of visual screening on cervical cancer incidence and mortality in Tamil Nadu, India: a cluster-randomised trial. Lancet 2007; 370: 398–406. Sankaranarayanan R, Ramadas K, Thomas G, et al, for the Trivandrum Oral Cancer Screening Study Group. Eﬀect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial. Lancet 2005; 365: 1927–33. 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. 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. 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.
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Misoprostol for all women seeking abortion?
Published Online March 8, 2012 DOI:10.1016/S01406736(12)60037-3 See Articles page 1817
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, surgically 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 surgical 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 ﬁrm. In a large retrospective series,3 the use of laminaria before surgery
was associated with reduced uterine perforation and signiﬁcantly reduced cervical injury,4 and these eﬀects were enhanced when the abortion was done by a skilled practitioner. Rapidly acting osmotic dilators are available, but pharmaceutical approaches, including prostaglandin analogues and antiprogesterones, have also been developed.5 Although mifepristone is very eﬀective, it is expensive and needs a delay of 24 h for good eﬀect.6 Of the prostaglandin analogues, misoprostol has become prominent for both surgical and medical abortion,7 because it is eﬀective, easy to use, and cheap. Many studies5 have shown the eﬀectiveness 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. www.thelancet.com Vol 379 May 12, 2012