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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. 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. 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). 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. Bill & Melinda Gates Foundation.

Prior studies of squamous cell carcinoma of the head and neck (SCCHN) have explored the effect of socioeconomic status (SES) as an independent risk factor; however, none have investigated the interaction of known risk factors with SES. We examined this using the North Carolina Head and Neck Cancer Epidemiology Study, a population-based case–control study. Incident cases of SCCHN from North Carolina between 2002 and 2006 (n = 1,153) were identified and age, sex, and race-matched controls (n = 1,267) were selected from driver license records. SES measures included household income, educational attainment, and health insurance. Logistic regression was used to estimate adjusted odds ratios (OR) and 95 % confidence intervals (CI). Current smoking was more strongly associated with SCCHN among those households making < $ 20,000/year [OR 5.11 (3.61–6.61)] compared to household incomes > $ 50,000/year [OR 2.47 (1.69–3.25); p interaction < 0.001]. Current drinking was more strongly associated with SCCHN in household incomes < $ 20,000 [OR 2.91 (2.05–3.78)] compared to > $50,000/year [1.28 (0.97–1.58); p interaction < 0.001]. Current drinkers with less than high school education or income < $20,000 had nearly threefold odds of never-drinkers in the same SES category [OR 2.91 (2.05–3.78); 2.09 (1.39–2.78), respectively]. Our results suggest that the relationship of smoking and alcohol use may be stronger among those of lower SES.

In context of the ongoing multi-centric HPV vaccine study in India, unvaccinated married women (N = 1484) aged 18–23 years were recruited in 2012–2015 as age-matched controls to the vaccinated women and followed up yearly. We assess type-specific prevalence, natural history and potential determinants of human papillomavirus (HPV) infection in these unvaccinated women. Cervical samples were collected yearly for at least four consecutive years. A Multiplex Type-Specific E7-Based polymerase chain reaction assay was used to detect 21 HPV types. HPV prevalence was 36.4% during 6 years. Most common HPV types were 16 (6.5%) and 31 (6.1%). Highest persistence were observed for HPV 35 (62.5%) and 52 (25%). New HPV acquisition rate was 5.6/1000 person-months of observation (PMO), highest for HPV 16 (1.1/1000 PMO). Type-specific clearance rates ranged between 2.9–5.5/100 PMO. HPV 16 and/or 18 infections were 41% (95% CI 4–63%) lower among women with 2-<3 years between marriage and first cervical sample collection compared to those with <2 years. HPV prevalence and acquisition rates in young Indian women were lower than their Western counterparts. HPV 16 infections being most common shows the importance and potential impact of HPV vaccination in India. Women with 2–3 years exposure had reduced risk possibly due to higher infections clearance.

Abstract Background: Oral cancer is a major health problem in India. Recently an increase in the oral cancer incidence among young individuals without any habits was observed, which may be due to Human Papilloma Virus (HPV). However, information on the prevalence of HPV in oral cancer in India is sparse. This study aims to document the frequency of HPV16 infection in oral squamous cell carcinoma (SCC) and to study its correlation with treatment outcome. Methods: Paraffin-embedded tissue blocks of 183 patients with SCC of the oral cavity were studied. HPV16 prevalence was detected by a polymerase chain reaction and expression of p16INK4a was analyzed by immunohistochemistry. This was correlated with clinical outcomes. Results: The prevalence of HPV 16 was 6.6% and all were carcinoma tongue. All HPV-positive patients showed intense expression of p16INK4a. The five-year overall survival (OS) and disease-free survival (DFS) for HPV positive patients were higher compared to HPV negative patients (100% versus 74.5% and 100% versus 70.8% respectively). The five-year OS and DFS for patients with p16INK4a intense expression were also higher compared to p16INK4a weak expression (91.2% versus 57.4% and 82% versus 22.5% respectively). Five-year OS and DFS of patients with HPV16 positivity and p16INK4a intense expression were significantly higher than patients with HPV negative and p16INK4a weak expression (100% versus 54.7% and 100% versus 22.5% respectively). Conclusion: The frequency of HPV16 positivity in oral cancer was low in this study with a site predilection to the oral tongue. p16INK4a expression did not correlate with HPV status. A better treatment outcome was observed in HPV-positive cancers. We also observed better treatment outcomes in patients with p16INK4A overexpression irrespective of HPV status.

We investigated how somatic changes in HNSCC interact with environmental and host risk factors and whether they influence the risk of HNSCC occurrence and outcome. 180-paired samples diagnosed as HNSCC in two high incidence regions of Europe and South America underwent targeted sequencing (14 genes) and evaluation of copy number alterations (SCNAs). TP53, PIK3CA, NOTCH1, TP63 and CDKN2A were the most frequently mutated genes. Cases were characterized by a low copy number burden with recurrent focal amplification in 11q13.3 and deletion in 15q22. Cases with low SCNAs showed an improved overall survival. We found significant correlations with decreased overall survival between focal amplified regions 4p16, 10q22 and 22q11, and losses in 12p12, 15q14 and 15q22. The mutational landscape in our cases showed an association to both environmental exposures and clinical characteristics. We confirmed that somatic copy number alterations are an important predictor of HNSCC overall survival.

Worldwide use of formalin-fixed paraffin-embedded blocks (FFPE) is extensive in diagnosis and research. Yet, there is a lack of optimized/standardized protocols to process the blocks and verify the quality and presence of the targeted tissue. In the context of an international study on head and neck cancer (HNC)-HPV-AHEAD, a standardized protocol for optimizing the use of FFPEs in molecular epidemiology was developed and validated. First, a protocol for sectioning the FFPE was developed to prevent cross-contamination and distributed between participating centers. Before processing blocks, all sectioning centers underwent a quality control to guarantee a satisfactory training process. The first and last sections of the FFPEs were used for histopathological assessment. A consensus histopathology evaluation form was developed by an international panel of pathologists and evaluated for four indicators in a pilot analysis in order to validate it: 1) presence/type of tumor tissue, 2) identification of other tissue components that could affect the molecular diagnosis and 3) quality of the tissue. No HPV DNA was found in sections from empty FFPE generated in any histology laboratories of HPV-AHEAD consortium and all centers passed quality assurance for processing after quality control. The pilot analysis to validate the histopathology form included 355 HNC cases. The form was filled by six pathologists and each case was randomly assigned to two of them. Most samples (86%) were considered satisfactory. Presence of >50% of invasive carcinoma was observed in all sections of 66% of cases. Substantial necrosis (>50%) was present in <2% of samples. The concordance for the indicators targeted to validate the histopathology form was very high (kappa > 0.85) between first and last sections and fair to high between pathologists (kappa/pabak 0.21-0.72). The protocol allowed to correctly process without signs of contamination all FFPE of the study. The histopathology evaluation of the cases assured the presence of the targeted tissue, identified the presence of other tissues that could disturb the molecular diagnosis and allowed the assessment of tissue quality.

We performed an independent comparison of neutralizing and cross-neutralizing antibody (ab) levels seven months after initiation of three-dose, six-month vaccination schedules with the bivalent and quadrivalent human papillomavirus (HPV) vaccines in adolescent Finnish and Indian females, respectively. We used a semi-automated Pseudovirion-Based Neutralization Assay and observed significantly higher HPV16/18 peak ab-levels in bivalent as compared to quadrivalent vaccine recipients. Bivalent vaccine induced cross-neutralizing HPV31/33/45/52/58 antibodies significantly more frequently and to higher levels than the quadrivalent vaccine. The correlation of bivalent vaccine-induced HPV45 ab-levels with HPV16/18 ab-levels was stronger than that of corresponding quadrivalent vaccine-induced ab-levels, suggesting a qualitatively different cross-reactive response. Our findings on the comparison of the immunogenicity of two HPV vaccine tested in two different populations indicate that further head-to-head studies are warranted.

Genetic variants in nicotinic acetylcholine receptor and alcohol metabolism genes have been associated with propensity to smoke tobacco and drink alcohol, respectively, and also implicated in genetic susceptibility to head and neck cancer. In addition to smoking and alcohol, tobacco chewing is an important oral cancer risk factor in India. It is not known if these genetic variants influence propensity or oral cancer susceptibility in the context of this distinct etiology. We examined 639 oral and pharyngeal cancer cases and 791 controls from two case-control studies conducted in India. We investigated six variants known to influence nicotine addiction or alcohol metabolism, including rs16969968 (CHRNA5), rs578776 (CHRNA3), rs1229984 (ADH1B), rs698 (ADH1C), rs1573496 (ADH7), and rs4767364 (ALDH2). The CHRN variants were associated with the number of chewing events per day, including in those who chewed tobacco but never smoked (P =  0.003, P =  0.01 for rs16969968 and rs578776 respectively). Presence of the variant allele contributed to approximately 13% difference in chewing frequency compared to non-carriers. While no association was observed between rs16969968 and oral cancer risk (OR =  1.01, 95% CI =  0.83- 1.22), rs578776 was modestly associated with a 16% decreased risk of oral cancer (OR =  0.84, 95% CI =  0.72- 0.98). There was little evidence for association between polymorphisms in genes encoding alcohol metabolism and oral cancer in this population. The association between rs16969968 and number of chewing events implies that the effect on smoking propensity conferred by this gene variant extends to the use of smokeless tobacco.

Introduction The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing worldwide. High-risk human papillomavirus (HPV) infection is now a well-recognised risk factor for oropharyngeal cancers. However, the information regarding the prevalence and outcome of HPV-related OPSCC is sparse in India. The study was conducted to identify the frequency of HPV infection in oropharyngeal cancer and also to study the treatment response and survival according to HPV positivity and p16 expression. Materials and methods The study sample consists of 100 paraffin-embedded tissue blocks of histologically proven OPSCC patients who had undergone treatment at a tertiary cancer centre in Kerala, India, from January 2010 to December 2012. The patients' medical records were examined to obtain demographic data, information on habits, and clinical, histopathological, and treatment information. Follow-up information on disease status and vital status was collected until May 2023. Paraffin-embedded tissue blocks of these patients were collected from the archives of the Division of Pathology. Immunohistochemistry (IHC) was used to identify p16 expression. HPV DNA was isolated from the paraffin-embedded tissue blocks by polymerase chain reaction. Statistical analysis and results Survival curves were obtained using the Kaplan-Meier method and compared with the log-rank test. The influence of p16 status and HPV DNA positivity on survival and recurrence was assessed using Cox regression. A total of 100 patients diagnosed with oropharyngeal malignancy and their paraffin-embedded blocks were used for the present study. p16 IHC was invalid for three patients, and 16 patients had invalid HPV DNA. Two patients were excluded from survival analysis because they had both invalid HPV DNA and p16 expression. A total of 98 patients were included in the analysis. Out of 98 samples assessed, 47 tested positive for p16 expression, 48 were negative, and three showed invalid results. Among the 98 patients, HPV DNA results were available for 82 patients. HPV DNA positivity was reported in 25 patients, and 57 samples were HPV negative. There was no significant correlation between p16 expression and HPV status. The median follow-up was 134 months (1-160 months). The five-year overall survival (OS) probability was 42.6% (95% confidence interval (CI) 28.49-56.71) and 51.2% (95% CI 35.92-66.48), respectively, for p16-negative and p16-positive tumours (p=0.689). The corresponding figures for five-year disease-free survival (DFS) were 49.0% (95% CI 34.7-63.3) and 51.9% (95% CI 36.62-67.18), p=0.959. The five-year OS for HPV DNA-negative tumours was 45.5% (95% CI 32-59.02) compared to 49.1% (95% CI 28.72-69.48) in HPV DNA-positive tumours. There was an absolute difference of 20% in five-year OS between double-positive and double-negative tumours. Conclusion This study demonstrated a p16 positivity rate of 49.47% and an HPV DNA positivity rate of 30.37%. However, only 15.18% of cases showed double positivity. No significant correlation was observed between p16 expression and HPV status. Double positivity (p16 and HPV positive) was associated with better OS and DFS compared to double-negative (p16 and HPV negative) and single-positive (either p16 positive or HPV positive) cases. This subgroup of patients might benefit from potential de-escalation strategies and should be the target population for future studies.

In a review of strategies for preventing oral cancer, an expert panel reports that the use of tobacco (both smoking and smokeless), areca nut exposure, and heavy alcohol consumption are major contributors to this illness.