Immunogenicity and safety of a new quadrivalent HPV vaccine in girls and boys aged 9-14 years versus an established quadrivalent HPV vaccine in women aged 15-26 years in India: a randomised, active-controlled, multicentre, phase 2/3 trial.

BACKGROUND: To meet global cervical cancer elimination efforts, a wider range of affordable and accessible vaccines against human papillomavirus (HPV) are needed. We aimed to evaluate the immunogenicity and safety of a quadrivalent HPV vaccine (targeting HPV types 6, 11, 16, and 18), developed and manufactured by the Serum Institute of India (SIIPL). Here we report outcomes in the 9-14 years cohort. METHODS: This randomised, active-controlled, phase 2/3 trial was conducted at 12 tertiary care hospitals across India. Healthy participants aged 9-14 years or 15-26 years with no history of HPV vaccination were eligible for enrolment. Female participants were randomly assigned (1:1) with an interactive web response system, by use of a central computer-generated schedule and block randomisation (block sizes of 2, 4, 6, and 8), to receive the SIIPL quadrivalent HPV vaccine (Cervavac; SIIPL, Pune, India) or the comparator quadrivalent HPV vaccine (Gardasil; Merck Sharp & Dohme, Harleem, the Netherlands). Participants, investigators, laboratory technicians, and sponsors were masked to treatment allocation of female participants. Male participants were given the SIIPL quadrivalent HPV vaccine in an open-label manner. Study vaccines were administered intramuscularly with a two-dose schedule (at day 0 and 6 months) in the cohort aged 9-14 years, and with a three-dose schedule (at day 0, month 2, and month 6) in the cohort aged 15-26-years. Immunogenicity was assessed 30 days after the last dose by use of multiplexed ELISA. The primary outcome was the non-inferiority of immune response in terms of the geometric mean titre (GMT) of antibodies against HPV types 6, 11, 16, and 18 generated by the SIIPL quadrivalent HPV vaccine in girls and boys (aged 9-14 years) compared with the GMT generated by the comparator quadrivalent HPV vaccine in women aged 15-26 years at month 7 in the modified per-protocol population (ie, all participants who received all doses of study vaccines per assigned treatment group and had both day 0 and 1-month immunogenicity measurements after the last dose following protocol-defined window periods with no major protocol deviations). Non-inferiority was established if the lower bound of the 98·75% CI of the GMT ratio was 0·67 or higher. The co-primary outcome of occurrence of solicited adverse events (within 7 days of each dose) and unsolicited adverse events (up to 30 days after the last dose) was assessed in all participants who were enrolled and received at least one dose of study vaccine. The trial is registered with the Clinical Trials Registry - India (CTRI/2018/06/014601), and long-term follow-up is ongoing. FINDINGS: Between Sept 20, 2018, and Feb 9, 2021, 2341 individuals were screened, of whom 2307 eligible individuals were enrolled and vaccinated: 1107 (738 girls and 369 boys) in the cohort aged 9-14 years and 1200 (819 women and 381 men) in the cohort aged 15-26 years. No race or ethnicity data were collected. 350 girls and 349 boys in the SIIPL quadrivalent HPV vaccine group and 338 women in the comparator vaccine group were included in the modified per-protocol population for the primary endpoint analysis. The median follow-up for the analyses was 221 days (IQR 215-231) for girls and 222 days (217-230) for boys in the SIIPL quadrivalent HPV vaccine group, 223 days (216-232) for girls in the comparator vaccine group, and 222 days (216-230) for women in the comparator vaccine group. GMT ratios were non-inferior in girls and boys receiving the SIIPL quadrivalent HPV vaccine compared with women receiving the comparator vaccine: GMT ratios for girls were 1·97 (98·75% CI 1·67-2·32) for HPV type 6, 1·63 (1·38-1·91) for HPV type 11, 1·90 (1·60-2·25) for HPV type 16, and 2·16 (1·79-2·61) for HPV type 18. For boys the GMT ratios were 1·86 (1·57-2·21) for HPV type 6, 1·46 (1·23-1·73) for HPV type 11, 1·62 (1·36-1·94) for HPV type 16, and 1·80 (1·48-2·18) for HPV type 18. The safety population comprised all 1107 participants (369 girls and 369 boys in the SIIPL quadrivalent HPV vaccine group, and 369 girls in the comparator group). Solicited adverse events occurred in 176 (48%) of 369 girls and 124 (34%) of 369 boys in the SIIPL vaccine group and 179 (49%) of 369 girls in the comparator vaccine group. No grade 3-4 solicited adverse events occurred within 7 days of each dose. Unsolicited adverse events occurred in 143 (39%) girls and 147 (40%) boys in the SIIPL vaccine group, and 143 (39%) girls in the comparator vaccine group. The most common grade 3 unsolicited adverse event was dengue fever, in one (<1%) girl in the SIIPL vaccine group and three (1%) girls in the comparator group. There were no grade 4 or 5 adverse events. Serious adverse events occurred in three (1%) girls and three (1%) boys in the SIIPL vaccine group, and five (1%) girls in the comparator vaccine group. No vaccine-related serious adverse events were reported. There were no treatment-related deaths. INTERPRETATION: We observed a non-inferior immune response with the SIIPL quadrivalent HPV vaccine in girls and boys aged 9-14 years and an acceptable safety profile compared with the comparator vaccine. These findings support extrapolation of efficacy from the comparator vaccine to the SIIPL quadrivalent HPV vaccine in the younger population. The availability of the SIIPL quadrivalent HPV vaccine could help meet the global demand for HPV vaccines, and boost coverage for both girls and boys globally. FUNDING: Biotechnology Industry Research Assistance Council, Department of Biotechnology (DBT), Government of India, and Serum Institute of India.

Effectiveness of family-centred sexual health education and HPV self-sampling in promoting cervical cancer screening among hard-to-reach indian women in rural and tribal areas: a community-based pilot study.

BACKGROUND: While cervical cancer deaths have declined steeply in high-income countries due to the widespread use of the Papanicolaou test (Pap test), the same trend has not emerged in low or middle-income countries (LMICs). Access to screening in LMICs like India is limited due to barriers such as limited healthcare infrastructures, lack of sexual health education, and stigma demarcating sexually transmitted infections (STIs). HPV self-sampling (HPV-SS), a woman-centered and at-home method for screening, can be utilized as a unique screening tool to overcome some of these barriers. Our study examined the effectiveness of HPV-SS, supported by family-centred arts-based sexual health literacy on the uptake of cervical cancer screening among hard-to-reach women in rural and remote areas in India. METHODS: Our community-based mixed methods pilot study recruited 240 participants (120 women and 120 male partners or family members) through female Accredited Social Health Activists (ASHA) across 3 Indian villages of Shirgoan, Khodala, and Jamsar in Palghar district. Inclusion criteria included women ages 30-69 who were under or never screened (UNS) and their male partners/family members aged 18 or over. Knowledge and attitudes about cervical cancer and screening and their perceived stigma surrounding STI were assessed using validated scales prior to and after attending a 2-hour arts-based sexual health education (SHE). In addition, participants' uptake of cervical cancer screening was assessed after attendance in SHE. FINDINGS: Results revealed significant improvement in knowledge and attitudes about cervical cancer and screening, and a reduction in the STI stigma after participation in SHE sessions (overall mean difference in Knowledge: z = 6.1 ± 2.4, P < 0.001; attitudes about Pap-test and VIA: z = 2.2 ± 8.4, P < 0.001 and z = 2.9 ± 8.2, P < 0.001; STI stigma: z = 2.8 ± 12.4, P < 0.001). 118 out of 120 female participants chose to be screened and 115 opted for HPV-SS. CONCLUSIONS: The implementation of HPV-SS coupled with family-centered arts-based and culturally appropriate SHE is highly promising in promoting cervical cancer screening among hard-to-reach women. Evidence from our study can be used to advance public health policies and inform the scale-up of similar initiatives in other villages and states across rural India and other LMICs.

Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study.

BACKGROUND: A randomised trial designed to compare three and two doses of quadrivalent human papillomavirus (HPV) vaccine in adolescent girls in India was converted to a cohort study after suspension of HPV vaccination in trials by the Indian Government. In this Article, the revised aim of the cohort study was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years post vaccination. METHODS: In the randomised trial, unmarried girls aged 10-18 years were recruited from nine centres across India and randomly assigned to either two doses or three doses of the quadrivalent HPV vaccine (Gardasil [Merck Sharp & Dohme, Whitehouse Station, NJ, USA]; 0·5 mL administered intramuscularly). After suspension of recruitment and vaccination, the study became a longitudinal, prospective cohort study by default, and participants were allocated to four cohorts on the basis of the number vaccine doses received per protocol: the two-dose cohort (received vaccine on days 1 and 180 or later), three-dose cohort (days 1, 60, and 180 or later), two-dose default cohort (days 1 and 60 or later), and the single-dose default cohort. Participants were followed up yearly. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Married participants were screened for cervical cancer as they reached 25 years of age. Unvaccinated women age-matched to the married vaccinated participants were recruited to serve as controls. Vaccine efficacy against persistent HPV 16 and 18 infections (the primary endpoint) was analysed for single-dose recipients and compared with that in two-dose and three-dose recipients after adjusting for imbalance in the distribution of potential confounders between the unvaccinated and vaccinated cohorts. This trial is registered with ISRCTN, ISRCTN98283094, and ClinicalTrials.gov, NCT00923702. FINDINGS: Vaccinated participants were recruited between Sept 1, 2009, and April 8, 2010 (date of vaccination suspension), and followed up over a median duration of 9·0 years (IQR 8·2-9·6). 4348 participants had three doses, 4980 had two doses (0 and 6 months), and 4949 had a single dose. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95·4% (95% CI 85·0-99·9) in the single-dose default cohort (2135 women assessed), 93·1% (77·3-99·8) in the two-dose cohort (1452 women assessed), and 93·3% (77·5-99·7) in three-dose recipients (1460 women assessed). INTERPRETATION: A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and 18, the genotypes responsible for nearly 70% of cervical cancers, to that provided by two or three doses. FUNDING: Bill & Melinda Gates Foundation.

Screening for breast cancer: Cost-effective solutions for low- & middle-income countries.

Low- and middle-income countries (LMICs) have limited financial resources and proportionately smaller portions allocated for health budget. With competing health priorities, treatment of the diagnosed cases and establishment of treatment facilities are the main concerns in LMICs. Infectious diseases, reducing infant, child and maternal mortality may seem crucial as compared to early cancer detection. LMICs that are committed to providing comprehensive cancer care, will need to judiciously choose the screening tool depending on specifics of how the tool is expected to perform in the population and the cost-effectiveness with respect to the number of lives expected to be saved. Increasing awareness about breast health in general and common cancers and non communicable diseases (NCDs), in particular, may lead to symptomatic women approaching the healthcare facilities at an earlier stage. When the limited available resources are mobilized towards cancer screening, increasing awareness would lead to greater acceptability of the programme. The reach of the programme to achieve good population coverage, the establishment of the diagnostic referral linkages and the availability and accessibility of treatment facilities, will all decide the outcome of the screening programme.

Narrow band imaging observed oral mucosa microvasculature as a tool to detect early oral cancer: an Indian experience.

BACKGROUND: Narrow band imaging (NBI) is a novel method with the potential to improve the diagnostic capability of white-light. METHODS: A prospective observational study of 50 consecutive patients, with suspicious malignant/premalignant lesions. White-light images were assessed as suspicious for malignancy/negative for malignancy, whereas NBI images were classified based on the IPCL patterns. All lesions underwent biopsy and accuracy was compared with the histopathology (Fig. 1). Fig. 1 Representative images of the IPCL patterns from Types I-IV RESULTS: 25 lesions (49%) were positive for malignancy, 2 (3.9%) lesions showed severe dysplasia, and 24(47%) were considered negative on histopathology. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of white light and NBI in detecting invasive carcinoma was 74.07%, 79.17%, 80.00%, 73.08% and 76.47%, and 92.67%, 90.16%, 92.56%, 91.67% and 92.16% respectively. The NBI group had a significantly better sensitivity and specificity to white light. The interobserver concordance was κ = 0.881. CONCLUSION: NBI is a highly effective tool to detect invasive carcinomas amongst suspicious lesions of the oral cavity.

Knowledge of symptoms and risk factors of breast cancer among women: a community based study in a low socio-economic area of Mumbai, India.

BACKGROUND: Breast cancer (BC) is leading cancer among women in India accounting for 27% of all cancers among women. Factors that make the policymakers and public health system worried are rising incidence of breast cancer in India and more importantly high death rates among breast cancer patients. One of the leading causes of high breast cancer deaths is lack of awareness and screening leading to the late presentation at an advanced stage. Therefore, the current research aimed to understand the knowledge of breast cancer symptoms and risk factors among women in a low socio-economic area of Mumbai. METHODS: A cross-sectional study was conducted at Prabhadevi, Mumbai and primary data was collected from 480 women aged 18-55 years. Structured questionnaire was used to collect quantitative data pertaining to awareness, signs and symptoms of breast cancer. Bivariate and multivariate regression techniques were used for understanding of the socio-demographic differentials in breast cancer awareness among women. RESULTS: The study found that around half (49%) of the women were aware of breast cancer. The women who were aware of breast cancer considered lump in breast (75%), change in shape and size of breast (57%), lump under armpit (56%), pain in one breast (56%) as the important and common symptoms. Less than one-fifth of the women who were aware of breast cancer reported early menstruation (5.6%), late menopause (10%), hormone therapy (13%), late pregnancy (15%) and obesity (19%) as the risk factors for breast cancer. The multivariate regression analysis showed women who had more than 10 years of schooling (Adjusted Odds Ratio: 3.93, CI: 2.57-6.02, P < 0.01) were about 4 times more likely to be aware of breast cancer than women who had less than 10 years of schooling. CONCLUSION: In conclusion, knowledge of danger signs and risk factors of breast cancer were low among women in the community. This may lead to late detection of breast cancer among women in the community. Therefore, the study calls for advocacy and larger intervention to enhance knowledge of breast cancer among women in the particular region with a special reference to women with low education.

Compliance with point-of-sale tobacco control policies and student tobacco use in Mumbai, India.

BACKGROUND: We measured how student tobacco use and psychological risk factors (intention to use and perceived ease of access to tobacco products) were associated with tobacco vendor compliance with India's Cigarettes and Other Tobacco Products Act provisions regulating the point-of-sale (POS) environment. METHODS: We conducted a population-based cross-sectional survey of high school students (n=1373) and tobacco vendors (n=436) in school-adjacent communities (n=26) in Mumbai, India. We used in-class self-administered questionnaires of high school students, face-to-face interviews with tobacco vendors and compliance checks of tobacco POS environments. Logistic regression models with adjustments for clustering were used to measure associations between student tobacco use, psychological risk factors and tobacco POS compliance. RESULTS: Compliance with POS laws was low overall and was associated with lower risk of student current tobacco use (OR 0.48, 95% CI 0.26 to 0.91) and current smokeless tobacco use (OR 0.40, 95% CI 0.21 to 0.77), when controlling for student-level and community-level tobacco use risk factors. Compliance was not associated with student intention to use tobacco (OR 0.50; 95% CI 0.21 to 1.18) and perceived ease of access to tobacco (OR 0.73; 95% CI 0.53 to 1.00). CONCLUSIONS: Improving vendor compliance with tobacco POS laws may reduce student tobacco use. Future studies should test strategies to improve compliance with tobacco POS laws, particularly in low-income and middle-income country settings like urban India.

Smokeless tobacco use and oral neoplasia among urban Indian women.

OBJECTIVES: Oral cavity cancers are fourth most common cancers among Indian women. The objectives were to create cancer awareness (CA) and screen tobacco-using women for oral cavity cancers. MATERIALS AND METHODS: A community-based CA and screening programme was conducted among women in Mumbai, India. The tobacco-using women participated in CA and oral cavity screening by oral visual inspection (OVI). All screen-positive women were referred to nodal hospital and assisted for diagnostic confirmation and treatment completion. RESULTS: Twelve slum clusters comprising of 138,383 population and 13,492 tobacco-using women have been covered. Among them, 11,895 (88.2%) participated in CA and 11,768 (87.2%) in OVI. A total of 377 (3.2%) women were screened positive, 275 (72.9%) complied with referral and 207 oral precancers [173 leukoplakia, 9 erythroplakia, 3 erythroleukoplakia and 41 sub-mucus fibrosis (SMF) including 35 women with multiple precancers] and 7 oral cancers were diagnosed. The detection rate of oral precancerous lesions and oral cancers was 17.6 and 0.6 per 1,000 screened women. Thirty-five women had multiple oral precancerous lesions. The results of multivariate analysis indicate dose-response relationship between tobacco use and risk of oral precancers. CONCLUSION: Good participation rates (>85%) for cancer awareness and OVI were seen among urban slum women in India. Many oral precancer and cancer cases were detected and were managed at the nodal hospital.

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

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.

Prevention of Cervix Cancer in India.

Cervical cancer is the fourth most common cancer among women globally and the second most common cancer among Indian women. India alone bears 23% of the global cervical cancer burden. In India, population-based cervical cancer screening is largely nonexistent in most regions due to competing healthcare priorities, insufficient financial resources and a limited number of trained providers. Hence, most of the cases present in advanced stages of the disease, thus leading to increased mortality and reduced survival. Various screening options like cytology, visual-based screening and testing for high-risk HPV are available. Several cross-sectional studies have looked at the comparative efficacy of different screening tests. Three important randomized controlled trials from India have shown the efficacy of screening once in a life time with HPV DNA, one-time screening with VIA by trained nurses and four-time screening with VIA by trained primary health workers, reducing mortality due to cervical cancers. Prevention of cervical cancers with two-dose HPV vaccination and early detection of precancerous cervical lesions of the eligible population through screening and their appropriate treatment with a single-visit 'screen-and-treat' approach appear to be promising for low-middle-income countries including India.

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.

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

BACKGROUND: India's 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.

Behavioural interventions for tobacco cessation in India: A systematic review and meta-analysis.

Tobacco consumption is an area of public health concern in India. One of the unmet needs of many low-resource countries is to provide cost-effective tobacco cessation interventions for reducing tobacco-related mortality. This article reviews studies on non-pharmacological interventions for tobacco cessation in India. A systematic review by PICO (population, intervention, comparison, outcome) of behavioural intervention-based tobacco cessation studies that met the inclusion criteria, with a minimum 1-month follow-up, reporting outcomes in terms of frequencies or percentages published between 2010 and 2020 was performed. Following the review stages, 16 studies comprising 9,613 participants were included in the review. A pooled estimate was derived using both fixed-effects and random-effects models. The intervention showed good overall efficacy for any tobacco user (relative risk [RR] = 1.73 [95% confidence interval [CI]: 1.58-1.90) (fixed-effect model)] and (RR = 2.02 [95% CI: 1.64-2.48] [random-effects model]). Behavioural intervention studies targeted towards only smokers (RR of 1.81 [95% CI: 1.55-2.11] and 1.96 [95% CI: 1.52-2.53]) and combined smoking and smokeless tobacco users (RR of 1.69 [95% CI: 1.50-1.90] and 2.12 [95% CI: 1.49-3.01]) were equally efficacious. The review provides the effectiveness of behavioural interventions in quitting tobacco among users of both smoking and smokeless forms of tobacco. The review findings are of particular significance to inform health policy decisions on the integration of cost-effective brief behavioural intervention into existing health care services in resource-constrained countries.

Health-Related Quality of Life (HRQoL) Using EQ-5D-5L: Value Set Derived for Indian Breast Cancer Cohort.

OBJECTIVE: The purpose of this study was to report quality of life of newly diagnosed breast cancer patients from India in a large cohort using the EQ-5D-5L instrument. METHODS: The study used longitudinal data of 500 breast cancer and 200 non-cancer subjects registered at our centre, during June 2019 and March 2022. The EQ-5D-5L and EQ-VAS instruments were used to measure and compare utility scores among cancer and non-cancer subjects. Descriptive statistics were analyzed and Tobit regression model were used to confirm the predictors of the utility score. RESULTS: The cancer subjects had a mean EQ-ED-5L utility score of 0.8703 (SD=0.121), 0.8745 (SD=0.094) and 0.8902 (SD=0.107) at the time of baseline, completion and follow up surveys respectively.  EQ-5D-5L values had significantly worsened after diagnosis of cancer as compared to the non-cancer cohort (0.87 vs. 0.93, p value 0.000). EQ-5D-5L utility scores as per stage for the cancer cohort were 0.88, 0.86 and 0.83 respectively for stage I-II, III and IV. Similarly, the EQ-VAS scores for stage I-II, III and IV were 74.9, 72.6 and 73.2 respectively. Multivariate analysis confirmed strong association of age, religion and income with the utility-values. CONCLUSION: This is the first longitudinal study reporting the utility scores derived from a large cohort of breast cancer patients demonstrating lower utility scores compared to non-cancer cohort. The utility scores also improve post treatment completion for cancer patients and decrease with higher stage at diagnosis. This information will be useful for future health economic research in India pertaining to breast cancer.

Surviving the Storm: The Impact of COVID-19 on Cervical Cancer Screening in Low- and Middle-Income Countries.

According to the Center for Disease Control and Prevention's National Breast and Cervical Cancer Early Detection Program, the cervical cancer screening rate dropped by 84% soon after the declaration of the COVID-19 pandemic. The challenges facing cervical cancer screening were largely attributed to the required in-person nature of the screening process and the measures implemented to control the spread of the virus. While the impact of the COVID-19 pandemic on cancer screening is well-documented in high-income countries, less is known about the low- and middle-income countries that bear 90% of the global burden of cervical cancer deaths. In this paper, we aim to offer a comprehensive view of the impact of COVID-19 on cervical cancer screening in LMICs. Using our study, "Prevention of Cervical Cancer in India through Self-Sampling" (PCCIS), as a case example, we present the challenges COVID-19 has exerted on patients, healthcare practitioners, and health systems, as well as potential opportunities to mitigate these challenges.

Novel educational training of para medical professionals in cervical cancer screening.

Background: Cervical cancer is a public health problem in India due to weak national screening policy compounded by lack of resources including scarcity of trained personnel to carry out community-based screening program. Para medical professionals (PMPs) are closely related to women in local communities. Hence, training PMPs by incorporating novel technology and reduced time duration to achieve adequate competence in screening is an area underutilized and needs to be explored. Materials and methods: A pilot cross sectional analytical study was conducted at a tertiary referral cancer center using a shorter version of educational intervention of 2 weeks duration (EI2W) involving PMPs. Pre- and post-training assessment of knowledge, attitude, and practice (KAP) was done using questionnaires consisting of 5 domains viz. awareness of cervical cancer, awareness of cervical pre-cancer, practical screening methodology (practice oriented), data management and aspects of human papilloma virus (HPV). Wilcoxon signed-rank test was used for comparison and the degree of change was measured using analysis of covariance (ANCOVA). A p value of <0.05 was considered significant. Results: 118 PMPs were included. There was a significant improvement in scores of all domains (except cervical pre-cancer domain), following introduction of EI2W. Knowledge scores, post EI2W was better in Auxiliary Nurse Midwives (ANMs) than other participants. Awareness regarding cervical cancer was higher with more years of experience. The KAP analysis showed excellent interrater reliability in the practice 0.726 (0.649-0.792) followed by knowledge domain 0.711 (0.626-0.783). Conclusion: EI2W was effective in significantly improving the competence of PMPs, thus reducing human resource constraints in cervical cancer prevention and elimination.

Evaluation of immune response to single dose of quadrivalent HPV vaccine at 10-year post-vaccination.

BACKGROUND: The recent World Health Organization recommendation supporting single-dose of HPV vaccine will significantly reduce programmatic cost, mitigate the supply shortage, and simplify logistics, thus allowing more low- and middle-income countries to introduce the vaccine. From a programmatic perspective the durability of protection offered by a single-dose will be a key consideration. The primary objectives of the present study were to determine whether recipients of a single-dose of quadrivalent HPV vaccine had sustained immune response against targeted HPV types (HPV 6,11,16,18) at 10 years post-vaccination and whether this response was superior to the natural antibody titres observed in unvaccinated women. METHODS: Participants received at age 10-18 years either one, two or three doses of the quadrivalent HPV vaccine. Serology samples were obtained at different timepoints up to 10 years after vaccination from a convenience sample of vaccinated participants and from age-matched unvaccinated women at one timepoint. The evolution of the binding and neutralizing antibody response was presented by dose received. 10-year durability of immune responses induced by a single-dose was compared to that after three doses of the vaccine and in unvaccinated married women. RESULTS: The dynamics of antibody response among the single-dose recipients observed over 120 months show stabilized levels 18 months after vaccination for all four HPV types. Although the HPV type-specific (binding or neutralizing) antibody titres after a single-dose were significantly inferior to those after three doses of the vaccine (lower bounds of GMT ratios < 0.5), they were all significantly higher than those observed in unvaccinated women following natural infections (GMT ratios: 2.05 to 4.04-fold higher). The results correlate well with the high vaccine efficacy of single-dose against persistent HPV 16/18 infections reported by us earlier at 10-years post-vaccination. CONCLUSION: Our study demonstrates the high and durable immune response in single-dose recipients of HPV vaccine at 10-years post vaccination.

Impact of age at vaccination and cervical HPV infection status on binding and neutralizing antibody titers at 10 years after receiving single or higher doses of quadrivalent HPV vaccine.

Long-term follow-up of a cohort of unmarried girls who received one, two, or three doses of quadrivalent HPV vaccine, between 10 and 18 years of age, in an Indian multi-centric study allowed us to compare antibody responses between the younger and older age cohorts at 10-years post-vaccination, and study the impact of initiation of sexual activity and cervical HPV infections on antibody levels. Among the younger (10-14 years) recipients of a single dose, 97.7% and 98.2% had detectable binding antibody titers against HPV 16 and HPV 18 respectively at ten years post-vaccination. The proportions among those receiving a single dose at age 15-18 years were 92.3% and 94.2% against HPV 16 and HPV 18 respectively. Mean HPV 16 binding antibody titers were 2.1 folds (95%CI 1.4 to 3.3) higher in those vaccinated at ages 10-14 years, and 1.9 folds (95%CI 1.2 to 3.0) higher in those vaccinated at 15-18 years compared to mean titers seen in the unvaccinated women. Compared to previous timepoints of 36 or 48 months, binding antibodies against HPV 16 and neutralizing antibodies against both HPV 16 and HPV 18 were significantly higher at 10 years. This rise was more pronounced in participants vaccinated at 15-18 years. No association of marital status or cervical HPV infections was observed with the rise in titer. Durability of antibody response in single dose recipients correlated well with the high efficacy of a single dose against persistent HPV 16/18 infections irrespective of age at vaccination, as we reported earlier.

Cancer cervix: Epidemiology and disease burden.

Cervical cancer remains a major public health problem, ranking as the fourth most common cause of cancer incidence and mortality in women worldwide. Wide variations in cervical cancer incidence and mortality were observed with highest incidence rates in Sub Saharan Africa and with 85% of deaths occurring in developing regions of the world. Non-existent or inadequate screening in public health care settings and limited access to the standard treatment options explains the large geographic variation in cervical cancer rates. Persistent infection with high-risk Human papillomavirus (HPV) types is the major risk factor for cervical cancer. High parity, long-term use of oral contraceptive pills, tobacco consumption, co-infection with other sexually transmitted agents, lifestyle factors such as multiple sexual partners, younger age at first sexual intercourse, immunosuppression, and diet have been identified as the co-factors most likely to influence the risk of acquisition of HPV infection and its further progress to cervical carcinogenesis. Differential screening rates and changes in epidemiological patterns have contributed to decreasing trends in cervical cancer in some developed regions of the world. Lower rates were also observed in North Africa and the Middle East, which may be attributed to cultural norms and conservative sexual behaviors. Across world regions, HPV prevalence was highest in women younger than 35 years of age, declining to a plateau in middle age and showed significant association between national age standardized incidence rates and corresponding estimates of HPV prevalence. The five most common HPV types in HPV-positive women worldwide were HPV16, HPV18, HPV31, HPV58, and HPV52, representing 50% of all HPV infections with HPV-16 and HPV-18 infections accounting for about 70% of the total infection burden. Tracking changing trends in the cervical cancer epidemiological patterns including HPV genotypes will immensely contribute toward effective prevention and control measures for cervical cancer elimination.

Tobacco and cancer awareness program among school children in rural areas of Ratnagiri district of Maharashtra state in India.

Background: Promoting awareness of tobacco and cancer in the community needs multipronged efforts. We performed a study to evaluate whether we could raise awareness about the harmful effects of tobacco, oral and esophageal cancer among school students by providing them health education. Moreover, we also compared the awareness level in students of age group 12 to ≤14 years with the age group >14 to 18 years. Methods: We conducted an awareness program in the schools of Ratnagiri district of Maharashtra state. Students aged 12-18 years participated in this study. We provided health education to school students using a standard presentation; the presentation was rich in illustrations depicting the harmful effects of tobacco as well as oral and esophageal cancer's signs, symptoms, diagnosis, treatment, and preventive measures. After the health talk, a questionnaire was circulated. The questions were focused on tobacco, signs, and symptoms of the diseases along with early detection, prevention, and treatment of cancer. Results: A total of 1354 students participated in the program. Totally, 567 (41.9%) students were from 6th to 8th grade (Group A, age group 12 to ≤14) and 787 (58.1%) students were from 9th to 12th standards (Group B, age group >14 to 18). Overall scores were high, ranging from 69% to 98%. Group A scored in the range of 69% to 95%, and Group B scored in the range 72%-98% The difference between the two groups was found to be statistically significant (P-value ≤0.05). Conclusion: A standardized health education program helped to raise awareness about the harmful effects of tobacco and cancer amongst school children. Further studies are needed to evaluate whether educating school children has an impact on community understanding of the disease.