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Sankaranarayanan R.,The Detection Group | Prabhu P.R.,Rajiv Gandhi Center for Biotechnology | Pawlita M.,German Cancer Research Center | Gheit T.,International Agency for Research on Cancer | And 35 more authors.
The Lancet Oncology | Year: 2016

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 21258 eligible girls identified at 188 clusters, 17729 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. © 2016 International Agency for Research on Cancer. Published by Elsevier Ltd/Inc/BV. All rights reserved. Source

Thulaseedharan J.V.,Sree Chitra Tirunal Institute for Medical Science and Technology | Thulaseedharan J.V.,University of Tampere | Malila N.,University of Tampere | Esmy P.O.,Christian Fellowship Community Health Center | And 3 more authors.
International Journal of Gynecology and Obstetrics | Year: 2015

Objective To estimate the long-term risk of cervical cancer among women screened by visual inspection with acetic acid (VIA) and to evaluate the benefit of additional colposcopy triage in rural south India. Methods A retrospective analysis was conducted among 31 343 women who had undergone VIA at Dindigul district, India between January 1, 2000, and August 5, 2003, as part of a randomized screening trial. Women with positive VIA test results were offered colposcopy triage by trained nurses. Cervical cancer incidence data during follow-up (January 1, 2000, to December 31, 2012) were obtained from a regional cancer registry. Results Among 3021 screen-positive women free of cancer at baseline, 2974 women underwent colposcopy; colposcopic abnormalities suggestive of precancerous lesions were detected among 2792 of these women (93.9%). Compared with the women with negative VIA screening results, the hazard ratio (HR) of cervical cancer during follow-up among the VIA-positive women without colposcopic abnormalities was 6.5 (95% confidence interval [CI], 1.6-27.1). The risk was similar among VIA-positive women with colposcopic abnormalities but without histological confirmation (HR 5.2; 95% CI, 1.9-14.6). Conclusion The high risk of cancer among women without colposcopic abnormalities who tested positive by VIA suggested that screening without triage is potentially effective. © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. Source

Sankaranarayanan R.,The Detection Group | Nessa A.,Bangabandhu Sheikh Mujib Medical University | Esmy P.O.,Christian Fellowship Community Health Center | Dangou J.-M.,World Health Organization
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2012

The need for simple, cost-effective screening approaches for cervical cancer prevention in low-resource countries has led to the evaluation of visual screening with 3-5% acetic acid. The low reproducibility and wide variation in accuracy reflect the subjective nature of the test. Pooled sensitivity, specificity, positive and negative predictive values were 80%, 92%, 10% and 99%, respectively, for detecting cervical intraepithelial neoplasia grade 2 or worse lesions. Realistic sensitivity of a quality- assured single visual inspection with acetic acid is around 50%. A single round of visual inspection with acetic acid screening has been associated with a 25-35% reduction in cervical cancer incidence and the frequency of cervical intraepithelial neoplasia grade 2 or worse lesions in randomised-controlled trials. Despite all its limitations, implementing visual inspection with acetic acid screening in low-resource countries may provide a pragmatic approach to building up human resources and infrastructure that may facilitate the highly anticipated low-cost, rapid human papilloma virus testing in the near future. © 2011 Elsevier Ltd. All rights reserved. Source

Thulaseedharan J.V.,Sree Chitra Tirunal Institute for Medical Science and Technology | Thulaseedharan J.V.,University of Tampere | Malila N.,University of Tampere | Swaminathan R.,Cancer Institute WIA | And 5 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2015

Background: Socioeconomic factors are associated with screening in terms of reducing the risk of cervical cancer. This study aimed to clearly establish the effect of screening on variation in socio-economic factor-specific survival estimates. Materials and Methods: Survival estimates were calculated using the life table method for 165 women from the routine care control arm and 67 from the visual inspection with acetic acid screening arm diagnosed with cervical cancer during 2000-2006 in rural south India. Kaplan-Meier survival curves were plotted to compare the variation in survival by socioeconomic factors. Results: Whereas there was a significant variation in survival estimates of the different categories of age at diagnosis among the screen-detected cancers with women aged <50 years having an improved survival, no significant variation was noted among women diagnosed with cervical cancer from the control arm. Compared to the variation among the cancer cases detected in the unscreened control group, screening widened the variation in survival estimates by age and type of house, and reduced the variation by education. The direction of the magnitude of the survival estimates was reversed within the different categories of occupation, marital status and household income in the screen-detected cancer cases compared to control group cancer cases. Also, women diagnosed with stage 1 disease had a very good survival. Conclusions: Screening changed the pattern of survival by socio-economic factors. We found improved survival rates in screened women aged <50 years, with no formal education, manual workers and married women. Source

Thulaseedharan J.V.,Sree Chitra Tirunal Institute for Medical Science and Technology | Thulaseedharan J.V.,University of Tampere | Malila N.,University of Tampere | Hakama M.,University of Tampere | And 5 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2013

Background: Prospective cohort studies to determine cofactors with oncogenic HPV- infections for cervical cancer are very rare from developing countries and such data are limited to the few screening trials. Large screening trials provide such data as a by product. Some of the cases are prevented by screening and do not surface as invasive cancers at all. Also, pre-invasive lesions are detected almost entirely by screening. Screening causes selection bias if attendance in or effectiveness of screening is correlated with the risk factors. The aim of this study was to quantify the influence of screening on risk factors for cervical cancer. Materials and Methods: Our material stems from a rural cohort of 80,000 women subjected to a randomised screening trial. The effect of screening on the incidence of cervix cancer was estimated with reference to socio-demographic and reproductive risk factors of cervical cancer. We compared these risks with the incidence of cancer in the randomised control population by the same determinants of risk. Results: The results in the screening arm compared to the control arm showed that the women of low SES and young age were benefitting more than those of high SES and old age. The relative risk by age (30-39 vs 50-59) was 0.33 in the control arm and 0.24 in the screening arm. The relative risk by education (not educated vs educated) was 2.8 in the control arm and 1.8 in the screening arm. The previously married women did not benefit (incidence 113 and 115 per 100,000 women years in control vs screening arms) whereas the effect was substantial in those married (86 vs 54). Conclusions: The results in controls were consistent with the general evidence, but results in attenders and nonattenders of the screening arm showed that screening itself and self-selection in attendance and effectiveness can influence the effect estimates of risk factors. The effect of cervical cancer screening programmes on the estimates of incidence of cervical cancer causes bias in the studies on etiology and, therefore, they should be interpreted with caution. Source

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