Sharmila Pimple

Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study

Summary Background An increase in worldwide HPV vaccination could be facilitated if fewer than three doses of vaccine are as effective as three doses. We originally aimed to compare the immunogenicity and frequency of persistent infection and cervical precancerous lesions caused by vaccine-targeted HPV after vaccination with two doses of quadrivalent vaccine on days 1 and 180 or later, with three doses on days 1, 60, and 180 or later, in a cluster-randomised trial. Suspension of the recruitment and vaccination due to events unrelated to our study meant that some enrolled girls could not be vaccinated and some vaccinated girls received fewer than the planned number of vaccinations by default. As a result, we re-analysed our data as an observational cohort study. Methods Our study was designed to be done in nine locations (188 clusters) in India. Participants were unmarried girls aged 10–18 years vaccinated in four cohorts: girls who received three doses of vaccine on days 1, 60, and 180 or later, two doses on days 1 and 180 or later, two doses on days 1 and 60 by default, and one dose by default. The primary outcomes were immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity after vaccination for the vaccine-targeted HPV types 16, 18, 6, and 11 and incident and persistent infections with these HPVs. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702. Findings Vaccination of eligible girls was initiated on Sept 1, 2009, and continued until April 8, 2010. Of 21 258 eligible girls identified at 188 clusters, 17 729 girls were recruited from 178 clusters before suspension. 4348 (25%) girls received three doses, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses at days 1 and 60, and 4950 (28%) received one dose. Immune response in the two-dose HPV vaccine group was non-inferior to the three-dose group (median fluorescence intensity ratio for HPV 16 1·12 [95% CI 1·02–1·23] and for HPV 18 1·04 [0·92–1·19]) at 7 months, but was inferior in the two-dose default (0·33 [0·29–0·38] for HPV 16 and 0·51 [0·43–0·59] for HPV 18) and one-dose default (0·09 [0·08–0·11] for HPV 16 and 0·12 [0·10–0·14] for HPV 18) groups at 18 months. The geometric mean avidity indices after fewer than three doses by design or default were non-inferior to those after three doses of vaccine. Fewer than three doses by design and default induced detectable concentrations of neutralising antibodies to all four vaccine-targeted HPV types, but at much lower concentration after one dose. Cervical samples from 2649 participants were tested and the frequency of incident HPV 16, 18, 6, and 11 infections was similar irrespective of the number of vaccine doses received. The testing of at least two samples from 838 participants showed that there was no persistent HPV 16 or 18 infections in any study group at a median follow-up of 4·7 years (IQR 4·2–5·1). Interpretation Despite the limitations imposed by the suspension of the HPV vaccination, our findings lend support to the WHO recommendation of two doses, at least 6 months apart, for routine vaccination of young girls. The short-term protection afforded by one dose of HPV vaccine against persistent infection with HPV 16, 18, 6, and 11 is similar to that afforded by two or three doses of vaccine and merits further assessment. Funding Bill & Melinda Gates Foundation.

An overview of prevention and early detection of cervical cancers

Cervical cancer still remains the most common cancer affecting the Indian women. India alone contributes 25.41% and 26.48% of the global burden of cervical cancer cases and mortality, respectively. Ironically, unlike most other cancers, cervical cancer can be prevented through screening by identifying and treating the precancerous lesions, any time during the course of its long natural history, thus preventing the potential progression to cervical carcinoma. Several screening methods, both traditional and newer technologies, are available to screen women for cervical precancers and cancers. No screening test is perfect and hence the choice of screening test will depend on the setting where it is to be used. Similarly, various methods are available for treatment of cervical precancers and the selection will depend on the cost, morbidity, requirement of reliable biopsy specimens, resources available, etc. The recommendations of screening for cervical cancer in the Indian scenario are discussed.

An overview of the tobacco problem in India

This is a review paper comprehensively encompassing the different aspects of tobacco control with particular reference to the Indian scenario. The information on prevalent tobacco habits in India, health hazards and environmental hazards due to tobacco use, passive smoking and its impact, economics of tobacco, legislation to control tobacco in India, the tobacco cessation services and the way ahead for effective tobacco control are discussed. Tobacco is a leading preventable cause of death, killing nearly six million people worldwide each year. Reversing this entirely preventable manmade epidemic should be our top priority. This global tobacco epidemic kills more people than tuberculosis, HIV/AIDS and malaria combined. This epidemic can be resolved by becoming aware of the devastating effects of tobacco, learning about the proven effective tobacco control measures, national programmes and legislation prevailing in the home country and then engaging completely to halt the epidemic to move toward a tobacco-free world. India is the second largest consumer of tobacco globally, and accounts for approximately one-sixth of the worlds tobacco-related deaths. The tobacco problem in India is peculiar, with consumption of variety of smokeless and smoking forms. Understanding the tobacco problem in India, focusing more efforts on what works and investigating the impact of sociocultural diversity and cost-effectiveness of various modalities of tobacco control should be our priority.

Banning tobacco sales and advertisements near educational institutions may reduce students’ tobacco use risk: evidence from Mumbai, India

Background Indias Cigarettes and Other Tobacco Products Act bans tobacco sales and advertisements within 100 yards of educational institutions. In school-adjacent neighbourhoods in Mumbai, we assessed adherence to these policies and whether tobacco vendor and advertisement densities were associated with students’ tobacco use. Methods High school students’ tobacco use was measured using a multistage cluster sampling survey (n=1533). Field geographic information systems data were obtained for all tobacco vendors and advertisements within 500 m of schools (n=26). Random-effects multilevel logistic regression was used to estimate associations of tobacco vendor and advertisement densities with ever tobacco use, current smokeless tobacco use and current tobacco use. Results There were 1741 tobacco vendors and 424 advertisements within 500 m of schools, with 221 vendors (13%) and 42 advertisements (10%) located within 100 m. School-adjacent tobacco vendor density within 100 m was not associated with the tobacco use outcomes, but tobacco advertisement density within 100 m was associated with all outcomes when comparing highest to lowest density tertiles: ever use (OR: 2.01; 95% CI 1.00 to 4.07), current use (2.23; 1.16, 4.28) and current smokeless tobacco use (2.01; 1.02, 3.98). Tobacco vendor density within 200, 300, 400 and 500 m of schools was associated with current tobacco use and current smokeless tobacco use, but not ever use. Conclusions The tobacco sales ban near educational institutions could be expanded beyond 100 m. Greater enforcement is needed regarding the current bans, particularly because advertisement density within 100 m of schools was associated with all students’ tobacco use outcomes.

Evaluation of colposcopy vs cytology as secondary test to triage women found positive on visual inspection test

BACKGROUND Colposcopic evaluation and guided biopsy is an important diagnostic step and standard of management for abnormal cytology smears in developed countries. AIM The present study evaluates the performance of colposcopy vs conventional cytology in estimating the presence and grade of cervical disease against the reference standard of histopathology as a secondary test modality to triage women found positive on primary screening by visual inspection with 5% acetic acid (VIA). SETTINGS AND DESIGN Colposcopy and directed biopsy were performed after primary screening for cervical cancer in an urban hospital cancer screening clinic between January 2000 and June 2005, in Mumbai, India. MATERIALS AND METHODS Healthy women (8863) in the age group of 35-65 years participated in the cervical cancer early detection program in the hospital and community cancer screening clinics in Mumbai. Women found positive on the primary screening test by VIA underwent diagnostic evaluation by Pap smear cytology and colposcopy evaluation with directed biopsies. STATISTICAL ANALYSIS Accuracy parameters and their 95% confidence intervals were calculated using 2 X 2 tables and standard formulae. RESULTS The test range of sensitivity of colposcopy for the detection of histologically confirmed cervical intraepithelial neoplasia grade 1+ (CIN1+) or CIN2+ was 58.0-74.7% and that of specificity was 57.5-92.9%. The sensitivity and specificity of cytology to detect CIN2+ was 57.4% and 99.4%, respectively. CONCLUSION Colposcopy is a good sensitive test for the detection of CIN and can be considered as a secondary testing tool to triage women found positive on VIA.

Global strategies for cervical cancer prevention.

Purpose of review Cervical cancer still remains the fourth most common cancer, affecting women worldwide with large geographic variations in cervical cancer incidence and mortality rates. There exist vast disparities in cervix cancer control and prevention efforts globally. The present review addresses the current developments in cervical cancer prevention and control across both high-income countries and low–middle income countries and attempts to identify new strategies that might help address the gaps in cervical cancer care disparities globally. Recent findings Paradigms for cervix cancer screening are changing in high-resource settings from cytology-based screening to adoption of molecular screening and cotesting to achieve program effectiveness. Low–middle income countries with larger burden of cervical cancer continue to face financial and logistic limitations to make both cervix cancer screening and human papillomavirus vaccine available to their populations. Alternative low-cost screening technologies, operationally feasible implementation strategies, reduction of cost of procurement and delivery approaches for human papillomavirus vaccine need assessment to decrease cancer care disparities. Summary Efforts directed toward cervix cancer prevention and early detection for improvements in cervical cancer outcomes of incidence and mortality have to be proportionately matched by access to acceptable standards of cancer care.

Predictors of Quitting Tobacco - Results of a Worksite Tobacco Cessation Service Program Among Factory Workers in Mumbai, India

BACKGROUND Tobacco cessation would provide the most immediate benefits of tobacco control to prevent tobacco related disease morbidity and mortality. METHODS A tobacco cessation program involving individual and group behavior therapy was implemented in three stages at a worksite. Tobacco quit rates were assessed at the end of each contact session. RESULTS Out of the 291 tobacco users identified, 224 participated in the tobacco cessation interventions. At the end of three interventions, 38 (17%) users had successfully quit tobacco use. Presence of clinical oral pre-cancer lesion was found to be associated with quitting (p =0.02 ). Also tobacco users with oral pre-cancer lesions were around three times more likely to quit than those with no lesions (OR= 2.70 95% C.I= 1.20 - 6.05). CONCLUSION Cost effective multi-pronged tobacco cessation approaches, inbuilt into other occupational health and welfare activities, are acceptable and feasible to achieve long term sustainable tobacco cessation programs at worksites.

Comparative evaluation of human papilloma virus-DNA test verses colposcopy as secondary cervical cancer screening test to triage screen positive women on primary screening by visual inspection with 5% Acetic acid

INTRODUCTION Visual inspection with 5% Acetic acid (VIA) as a low cost screening method has good sensitivity with the limitation of low specificity and low positive predictive values. The present study therefore evaluates the performance of secondary testing by human papillomavirus (HPV) test and Colposcopy in a single-visit screening approach to increase program effectiveness in limited health-care resources settings. MATERIALS AND METHODS In a cross-sectional cervical cancer screening trial, 3629 women (30-65 years) were screened by primary screening test VIA. VIA test positive women were subsequently tested for the presence of oncogenic HPV types by hybrid capture II and with colposcopy. The reference investigation histopathology was performed for all primary screen positive women. RESULTS Data for 3613 evaluable women showed 352 (9.7%) women positive on primary screening by VIA. VIA had a sensitivity of 93% (95% confidence interval (CI): 0.76-0.99) and specificity of 91% (95% CI: 0.90-0.92) respectively to detect the cervical intraepithelial neoplasia grade 2+ . HPV DNA and colposcopy as secondary tests to triage VIA positive women had a sensitivity of 61% (95% CI: 0.41-0.78), 43% (95% CI: 0.24-0.63) and specificity of 99% (95% CI: 0.99-1.00), 99% (95% CI: 0.99-0.99) respectively for detecting CIN2+ lesions. CONCLUSION Two step screening model combining highly sensitive low cost test like VIA for primary screening followed by more specific HPV DNA test as triage test for primary screen positive can be a cost-effective cervical screening strategy in resource constrained settings.

An integrated approach to worksite tobacco use prevention and oral cancer screening among factory workers in Mumbai, India.

BACKGROUND Tobacco control and cessation interventions are among the most cost effective medical interventions but health systems in low resource countries lack the infrastructure to promote prevention and cessation among tobacco users. Workplace settings have the potential to provide opportunities and access for tobacco prevention interventions. METHODS This is a single group study evaluating tobacco use prevention and cessation through a structured three stage intervention program for tobacco users comprising education on harmful effects of tobacco, oral cancer screening and behavior therapy for tobacco cessation at the worksite. RESULTS All the 739 workers who were invited participated in tobacco awareness program and were screened for oral pre cancer lesions. 291 (39.4%) workers were found to be users of tobacco in some form. Education, gender and alcohol use (p<0.0001) were some of the factors associated with tobacco user status. The prevalence of clinical oral precancer lesions among tobacco users was 21.6%. Alcohol consumption (p<0.001), the type of tobacco consumed (p<0.018), personal medical history of chronic diseases (p<0.007) and combined use of alcohol and tobacco (p<0.001) were some factors found to be associated with presence of oral pre cancer lesions. CONCLUSION An integrated approach for worksite based tobacco use prevention with oral cancer screening program showed good acceptance and participation and was effective in addressing the problem of tobacco consumption among the factory workers.

HPV vaccine: One, two, or three doses for cervical cancer prevention?

the HPV vaccine protection afforded by two doses and by one dose. Kreimer et al. based on the clinical efficacy data, argue that there is suggestive evidence that HPV vaccine program using two-dose regimen instead of the standard three-dose regimen could potentially vaccinate 50% more women and could reduce cervical cancer incidence more than a program that uses the same number of total doses but in fewer women.[4] The decision of the GAVI Alliance to support HPV vaccination in 2011, in combination with the acceptance of less than three dose schedule could increase the implementation of HPV vaccination programs in low-income countries.