Impact of introduction of endocervical brush on cytologic detection of cervical epithelial cell abnormalities: A clinical audit of 13-years' experience at a cancer research centre.

OBJECTIVE: To study the temporal trends in cytologic detection of cervical epithelial cell abnormalities (ECA) and to evaluate the impact of introduction of endocervical brush sampling on detection of ECA. STUDY DESIGN: This was a cross-sectional study of conventional cervical smears collected over a 13 year period (2006-2018). The study was divided into two time periods (TP)-TP1 (2006-2014, 67,437 smears) using only extended tip Ayre's spatula and TP2 (2015-2018; 36,746 smears) when Cytobrush Papsmear kit (Ayre's spatula + endocervical brush) was used. The unsatisfactory rate and detection rate of ECA was compared between the two TPs. RESULTS: The unsatisfactory rate reduced from 4.7 % in TP 1-1.5% in TP2 (P < 0.001). The frequency of ECA was 1.5 % in TP1 and 1.9 % in TP2 (P < 0.001). A significantly higher number of ASC-H and HSIL were detected in TP2. There was a substantial improvement (3.7 times) in detection of glandular abnormalities overall (P < 0.001), as also for both the qualifiers AGC- NOS (4.4 times) and AGC- FN (3.3 times) in TP2. CONCLUSIONS: Cervical sampling using combined spatula and endocervical brush reduces the unsatisfactory rate and improves the detection of both squamous and glandular precancerous lesions. Hence, this sampling procedure should be recommended for all laboratories practicing conventional cervical cytology.

Prevalence and risk factors associated with substance use in children: A questionnaire-based survey in two cities of Uttar Pradesh, India.

BACKGROUND: There is a sharp increase of substance use, particularly tobacco and alcohol, among schoolchildren. AIMS: A study was undertaken to assess the prevalence, age of initiation, and determinants for the uptake of tobacco and alcohol habits among ever-user students. SETTINGS AND DESIGN: This was a cross-sectional study conducted among school students. MATERIALS AND METHODS: Information on alcohol and tobacco use, age at initiation, peer influence, reason of initiation, etc., was collected from students of class 7th-12th(ages: 11-19 years) studying in schools of Noida and Ghaziabad cities, through a pretested self-administered questionnaire through multistage sampling design. Univariate analysis was done to assess the significance of various determinants. RESULTS: "Ever use of substance" (alcohol or tobacco) was found in 14.3% students and was 1.2 times more among boys in comparison to girls (P < 0.05). About 29.5% of these students initiated the habit before 11 years of age and its prevalence was significantly more among boys from government schools as compared to private schools. The habits were 2.2, 3.8, and 4.6 fold higher among students if the father, mother, siblings, or friends also used substances. Substance use was less frequent among children of white-collared father and more educated parents. One-third of students up took the habit to make friends. CONCLUSION: The rising prevalence of substance use among students is a threat to the society. Introducing a "substance use prevention policy" in schools to educate students about various adverse effects and refusal skills may help curb this menace.

Retention of Knowledge Levels of Health Care Providers in Cancer Screening Through Telementoring.

Purpose Every year > 450,000 individuals are diagnosed with cancer and approximately 350,000 die of it in India. The Ministry of Health and Family Welfare has released an Operational Framework for the Management of Common Cancers that highlights population-based cancer screening programs in primary health care facilities by health care providers (HCPs) and capacity building of HCPs. The purpose of this study is to present a low-cost training model that is highly suitable for resource-deficient settings, such as those found in India, through Extension for Community Health Outcome (ECHO), a knowledge-sharing tool, to enable high-quality training of HCPs. Materials and Methods An in-person, 3-day training program was conducted for 27 HCPs in the tribal primary health care center of Gumballi in Karnataka, India, to teach the basics of cancer screening in oral, breast, and cervical cancer. The training of HCPs was done using the ECHO platform while they implemented the cancer screening, thus enabling them to build the much needed knowledge and skill set to conduct cancer screening in their respective communities. Results The knowledge level of the HCPs was tracked before the intervention, immediately after the 3-day training program, and 6 months after the ECHO intervention, which clearly showed progressive acquisition and retention of knowledge. A marked improvement in knowledge level score from an average of 6.3 to 13.7 on a 15-point scale was noticed after the initial in-person training. The average knowledge further increased to a score of 14.4 after 6 months as a result of training using the ECHO platform. Conclusion ECHO is an affordable and effective model to train HCPs in cancer screening in a resource-constrained setting.

Glutathione S-transferase M1 and T1 Polymorphisms, Cigarette Smoking and HPV Infection in Precancerous and Cancerous Lesions of the Uterine Cervix.

Glutathione S-transferases (GSTs) play an important role in detoxification of carcinogenic electrophiles. The null genotypes in GSTM1 and GSTT1 have been implicated in carcinogenesis. Present study was planned to evaluate the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci in cervical carcinogenesis. The study was conducted in Lok Nayak hospital, New Delhi. DNA from clinical scrapes of 482 women with minor gynaecologic complaints attending Gynaecology OPD and tumor biopsies of 135 cervical cancer cases attending the cancer clinic was extracted. HPV DNA was detected by standard polymerase chain reaction (PCR) using L1 consensus primer pair. Polymorphisms of GSTM1 and GSTT1 were analysed by multiplex PCR procedures. Differences in proportions were tested using Pearson's Chi-square test with Odds ratio (OR) and 95% confidence interval (CI). The risk of cervical cancer was almost three times in women with GSTM1 homozygous null genotype (OR-2.62, 95%CI, 1.77-3.88; p<0.0001). No association of GSTM1 or GSTT1 homozygous null genotypes was observed in women with normal, precancerous and cervical cancerous lesions among ≤35 or >35 years of age groups. Smokers with null GSTT1 genotype had a higher risk of cervical cancer as compared to non-smokers (OR-3.01, 95% CI, 1.10-8.23; p=0.03). The results further showed that a significant increased risk of cervical cancer was observed in HPV positive smoker women with GSTT1 (OR-4.36, 95% CI, 1.27-15.03; p=0.02) and GSTM1T1 (OR-3.87, 95% CI, 1.05-14.23; p=0.04) homozygous null genotypes as compared to HPV positive non smokers. The results demonstrate that the GST null genotypes were alone not associated with the development of cervical cancer, but interacted with smoking and HPV to exert effects in our Delhi population.

GSTM1 and GSTT1 polymorphism and susceptibility to esophageal cancer in high- and low-risk regions of India.

Glutathione transferases, a super family of dimeric phase II metabolic enzymes play a vital role in biotransformation of many substances. This study evaluates the influence of genetic polymorphism of GSTM1 and GSTT1 gene loci on esophageal cancer risk in Assam and Delhi from India. DNA from blood samples of esophageal cancer cases (203,112) and controls (286,150) from Assam and Delhi, respectively, were extracted. GSTM1 and GSTT1 polymorphisms were analyzed by multiplex PCR procedure. Differences in proportions were tested using Pearson's chi-square test with odds ratio (OR) and 95 % confidence interval (CI). Risk of esophageal cancer was approximately twice in individuals having homozygous GSTM1 (OR-2.1, 95 % CI, 1.44-3.13) and GSTT1 null genotypes (OR-1.7,95 % CI, 0.99-2.77) in Assam, and around three times in GSTT1 null genotype (OR-2.9, 95 % CI, 1.56-5.27) in Delhi population. GSTM1 null genotype seems to play a protective role (OR-0.7, 95 % CI, 0.39-1.27) in Delhi. A significant association of GSTM1 null genotype with esophageal cancer was observed in a younger age group in Assam (OR-2.7, 95 % CI, 1.48-5.01), and in Delhi population association was observed in smokers with GSTT1 null genotype (OR-2.5, 95 % CI, 1.04-6.07), and alcoholics having GSTM1 null genotype (OR-2.6, 95 % CI, 0.99-6.77). Significant association of GSTM1 null genotype in Assam was observed between cancer cases and controls in fermented betel nut chewers only (OR-2.8, 95 % CI, 1.19-6.72), whereas, smoking and alcohol failed to show any correlation with GSTM1/GSTT1 genotypes. Cancer development is not only due to exogenous or endogenous carcinogens but depends on their interaction with genes that are involved in the detoxification of these carcinogens.

Clinical determinants and smear characteristics of unsatisfactory conventional cervicovaginal smears.

OBJECTIVE: To investigate clinical and cytomorphological determinants of unsatisfactory conventional Papanicolaou (Pap) smears. STUDY DESIGN: Records of 82,108 conventional cervicovaginal smears received over a ten-year period were retrieved. The significance of clinical determinants, viz. age (<45 or ≥45) and history of hysterectomy, radiotherapy (RT) and chemotherapy (CT), with respect to unsatisfactory outcomes was evaluated using univariate and multivariate analysis by logistic regression. Reasons for unsatisfactory results, i.e. cellularity, obscuration by blood or inflammation and drying artifact, were compared in the women managed by hysterectomy/RT/CT with those without these histories, using Chi square/Fischer's exact test. RESULTS: The overall unsatisfactory rate on conventional cervicovaginal cytology was 4.9%. For post-hysterectomy/RT/CT smears it was 12.5% while it was 4.6% for those without these histories. Age ≥45, and history of hysterectomy, RT or CT were all found to be significant for unsatisfactory outcomes (P<0.001), with the highest odds ratio for RT (2.81). Inadequate cellularity was the major reason for unsatisfactory cytology in both the treatment and non-treatment groups. Marked obscuring by blood was significantly more frequently associated with unsatisfactory tests in the treatment group (mainly in the post-radiotherapy smears) as compared to the control group (P<0.05). Multiple reasons were more commonly present in unsatisfactory smears from treatment group as compared to the control group (P<0.001). CONCLUSIONS: Older age and history of hysterectomy, RT or CT have a significant bearing on unsatisfactory outcome of Pap tests. Inadequate cellularity and obscuring blood are the main morphological determinants of unsatisfactory smears.

Risk factors associated with tobacco habits among adolescents: a cross-sectional school-based study.

BACKGROUND: The increase in tobacco use among adolescents in India is fraught with serious public health implications. The knowledge of factors which influence this habit could assist in tackling this problem. Hence, we aimed to determine factors associated with tobacco use among school students. METHODS: The increase in tobacco use among adolescents in India is fraught with serious public health implications. The knowledge of factors which influence this habit could assist in tackling this problem. Hence, we aimed to determine factors associated with tobacco use among school students. RESULTS: Of the 4786 students, 'current tobacco use' was reported by 197 (4.1%) students; 107 (2.2%) were exclusive smokers, 49 (1%) were exclusive tobacco chewers and 41 (0.9%) used both forms of tobacco. Tobacco use was less frequent among children of white collar than blue collar fathers (p<0.05) and also among children of more educated than less educated mothers (p<0.05). Tobacco use of father, mother, siblings and friends had a significant association with the student's tobacco use. The habits were 10.6-, 6.4-, 3.1- fold higher among students if they bought tobacco for teachers, brothers, father/relatives, respectively. Among tobacco users, 31.5% adopted these habits to refresh themselves, 45.9% preferred smoking outside home and 61% were influenced by actors smoking in films. CONCLUSION: Socioeconomic status, family and peer influence play an important role in students using tobacco.

Genetic polymorphisms of GSTM1 and GSTT1 genes in Delhi and comparison with other Indian and global populations.

The glutathione S-transferases (GSTs) are involved in the metabolism of many xenobiotics, including an array of environmental carcinogens, pollutants, and drugs. Genetic polymorphisms in these genes may lead to inter- individual variation in susceptibility to various diseases. In the present study, GSTM1 and GSTT1 polymorphisms were analysed using a multiplex polymerase chain reaction in 500 normal individuals from Delhi. The frequency of individuals with GSTM1 and GSTT1 null genotypes were 168 (33.6%) and 62 (12.4%) respectively, and 54 (10.8%) were having homozygous null genotype for both the genes GSTM1 and GSTT1 simultaneously. The studied population was compared with reported frequencies from other neighbouring state populations, as well as with those from other ethnic groups; Europeans, Blacks, and Asians. The prevalence of homozygous null GSTM1 genotype is significantly higher in Caucasians and Asians as compared to Indian population. The frequency of GSTT1 homozygous null genotypes is also significantly higher in blacks and Asians. We believe that due to large number of individuals in this study, our results are reliable estimates of the frequencies of the GSTM1, GSTT1 in Delhi. It would provide a basic database for future clinical and genetic studies pertaining to susceptibility and inconsistency in the response and/or toxicity to drugs known to be the substrates for GSTs.

Age at initiation & prevalence of tobacco use among school children in Noida, India: a cross-sectional questionnaire based survey.

BACKGROUND & OBJECTIVES: Tobacco use among school children is becoming a serious problem in developing countries. The early age of initiation underscores the urgent need to intervene and protect this vulnerable group from falling prey to this addiction. The present study was thus undertaken to assess the prevalence of tobacco habits among school children, determine the age of initiation of these habits, and compare the age of initiation between students who were more than 15 and ≤ 15 yr of age. METHODS: Data on tobacco use were collected from 4786 students of class 7 to 12 (age: 11-19 yr) studying in different private and government schools of Noida city during July- December 2005, through cluster and random sampling using a self-administered questionnaire. RESULTS: Any kind of tobacco use was found in 537 (11.2%) students; 419 (8.8%) were 'ever smokers (including current smokers)' 219 (4.6%) were 'ever tobacco chewers (including current chewers)', 179 (3.7%) were 'exclusive smokers' and 118 (2.5%) were 'exclusive tobacco chewers'. The mean age of initiation of these habits was around 12.4 yr. More than 50 per cent of tobacco chewers reported use of khaini at least once. Nearly 70 per cent of boys and 80 per cent of girls ≤ 15 yr initiated the habit of tobacco before the age of 11 yr. A significant early uptake of tobacco chewing was reported from private school students as compared to government school students (P<0.05). INTERPRETATION & CONCLUSIONS: Tobacco addiction is emerging as a big threat among children. Our findings indicate a recent downward shift in the age at initiation of tobacco uptake and rising prevalence among girls. Such data need to be collected from different parts of the country to develop anti-tobacco campaigns and take policy decision.

Hepatitis E virus infection and fulminant hepatic failure during pregnancy.

BACKGROUND AND AIM: Hepatitis E virus (HEV) infection leading to fulminant hepatic failure (FHF) and high mortality is a common feature in Indian women during the second and third trimesters of pregnancy. An altered status of hormones and immunity are observed during pregnancy but the actual cause of high mortality is still unknown. The present study was carried out to analyze CD3, CD4 and CD8 T cell counts and to assay the level of pregnancy-related hormones such as estrogen, progesterone and beta-HCG in order to discover the role played by these factors. METHODS: One hundred patients (50 pregnant and 50 non-pregnant women) with FHF and 150 pregnant healthy females without liver disease as controls were recruited for the study. Serological tests for all viral markers using ELISA kits and detection of HEV RNA by reverse transcription-polymerase chain reaction (RT-PCR) were carried out in all cases. CD3, CD4 and CD8 T cell counts were analyzed by fluorescence activated cell sorter (FACS) while hormone assay was performed by commercially available RIA kits. RESULTS: Serologically (38/50; 76%) as well as by RT-PCR (28/50; 56%), a significantly higher HEV positivity rate was found in pregnant FHF patients compared to non-pregnant women (serologically 15/50; 30%; RT-PCR 7/50; 14%). CD4 counts were lower (P < 0.05), while CD8 counts were higher (P < 0.05), and their ratio (CD4/CD8) in HEV positive pregnant FHF patients was significantly lower (P < 0.01) when compared to that of HEV negative pregnant FHF women or controls. Levels of estrogen, progesterone and beta-HCG were also found to be higher (P < 0.001) in HEV positive pregnant FHF patients when compared to HEV negative patients or controls. HEV infected pregnant FHF patients had a significantly higher mortality rate of 65.8% (25/38) compared to 23.5% (4/15) in HEV positive non-pregnant women (P < 0.001). CONCLUSIONS: Pregnancy appears to be a potential risk factor for viral replication and an extreme low immune status of Indian/Asian pregnant women. It is suggested that diminished cellular immunity (indicated by a decrease in CD4, an increase in CD8 cell counts and lowered CD4/CD8 cell ratio) and a high level of steroid hormones that influence viral replication/expression during pregnancy appear to be the plausible reasons for severity of the disease.

Spectrum of epithelial cell abnormalities of uterine cervix in a cervical cancer screening programme: implications for resource limited settings.

OBJECTIVE: (1) To compute the frequencies and peak age incidences of epithelial cell abnormalities (ECA) of uterine cervix in a cytology-based screening programme and (2) to analyze the comparative frequencies of squamous intraepithelial lesions (SIL) and malignancies in age groups <40 and > or =40 years, in order to assess the implications for screening protocol in resource limited settings. STUDY DESIGN: Pap smears form 29,475 women were cytologically screened over a 4-year period as a part of hospital-based screening programme. The frequencies, peak age incidences and mean age of various ECA detected were computed. The data was further stratified in to age groups <40 (Gp 1) and > or =40 (Gp 2) and comparative profile of the lesions was analyzed. RESULTS: On cytologic screening of the smears 5.6% ECA were detected. Atypical squamous cells-undetermined significance (ASC-US) and low grade SILs (LSIL) were diagnosed more frequently in Gp 1 (p<0.001) while atypical glandular cells (AGC) and malignancies were more significantly more frequent in Gp 2 (p<0.001). The frequency of HSIL was similar in the two groups. The SILs predominated in the fourth decade while the malignant lesions were most frequent in age >50 years. The mean age for LSIL and HSIL was 34.7 and 37.7 years, respectively, while for malignancy it was 51.8 years thus corroborating the hypothesis that a prolonged latent phase exists between the precursor lesions and the onset of invasive cancer. CONCLUSIONS: Since the goal of any screening programme should be to pick up majority of the precursor lesions and not frank cancers, it is desirable to initiate screening before 40 years of age. The WHO recommendation of once in a life time screening between 35 and 40 years of age seems appropriate for resource limited settings like ours.