Ashok Sehgal

Urine HPV-DNA detection for cervical cancer screening: prospects and prejudices.

Summary Oncogenic types of human papilloma viruses (HPVs) have been established to be the causative agents for cervical cancers and high-grade squamous intraepithelial lesions (HSILs). The clinical application of molecular tests for HPV detection for screening purposes has been of considerable interest. DNA amplification methods allow the use of self-collected samples (including urine) from material collected away from the original disease site. For screening of cervical pathology, detection of HPV-DNA in urine would be useful only if it represents cervical HPV infection and/or HPV-related cervical pathology. We conducted a review of the literature in order to ascertain: (1) if urine is an adequate sample for HPV-detection; (2) whether sensitive techniques are available for HPV-detection in urine and (3) if detection of HPV in urine truly represents cervical infection/pathology. The review process consisted of assembling facts and analysing the published literature on the following facts: anatomical considerations of the lower genital and the lower urinary tract, biological behaviour of HPV and its shedding behaviour, technical issues regarding sample collection, processing and HPV-DNA assay systems, concordance rates of HPV-DNA detection and their type specificity in the paired samples (urine and cervical scrapes) obtained in different clinico-epidemiological settings and comparative detection rates of HSILs in the paired samples.

Prevalence of high‐risk human papillomavirus type 16/18 infection among women with normal cytology: risk factor analysis and implications for screening and prophylaxis

Objective:u2002 To determine the prevalence of high‐risk human papillomavirus (HR‐HPV) 16/18 infection of uterine cervix among women in the reproductive age group, with cytologically normal cervical (Pap) smears; to analyse the risk factors for HR‐HPV acquisition and to address their implications for cervical cancer screening and prophylaxis in a low resource setting.

Age trends in pre-cancerous and cancerous lesions of the uterine cervix in a cytology screening programme: what should be the target age group for a major thrust of screening in resource-limited settings?

Objective:u2002 To identify the target age group where screening efforts may be concentrated in order to reduce the incidence of cervical cancer in resource‐limited countries.

Test characteristics of various screening modalities for cervical cancer: a feasibility study to develop an alternative strategy for resource‐limited settings

Objective:u2002 To determine test characteristics – sensitivity, specificity, positive and negative predictive values – of different screening modalities to detect cervical precancerous and cancerous lesions in order to devise an effective alternative strategy for cervical cancer screening in resource‐poor settings.

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 95xa0% confidence interval (CI). Risk of esophageal cancer was approximately twice in individuals having homozygous GSTM1 (OR-2.1, 95xa0% CI, 1.44–3.13) and GSTT1 null genotypes (OR-1.7,95xa0% CI, 0.99–2.77) in Assam, and around three times in GSTT1 null genotype (OR-2.9, 95xa0% CI, 1.56–5.27) in Delhi population. GSTM1 null genotype seems to play a protective role (OR-0.7, 95xa0% 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, 95xa0% CI, 1.48–5.01), and in Delhi population association was observed in smokers with GSTT1 null genotype (OR-2.5, 95xa0% CI, 1.04–6.07), and alcoholics having GSTM1 null genotype (OR-2.6, 95xa0% 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, 95xa0% 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.

Man power training for early cervical cancer detection.

Sir, Alternative strategies are being proposed for early detection of cervical cancer in developing countries. Several investigators have proposed that visual examination of the cervix is an alternative to cervical cytology screening (1–3). Training modules have been developed with success for paramedical staff, mainly nurses, auxiliary midwives and teachers (4, 5). Most of these studies were, however, conducted in research settings. In a real-time situation, trained staff of primary health centers are generally not available due to heavy duty schedules. Thus, one has to depend on community resources for manpower development. This is plentiful. We report our experience of training workers employed from the community for early cancer detection activities. The study was approved by the institutional ethical committee. Nine women, <28 years of age, all married and high schooleducated (non-medical), were recruited on a payment basis. They had no specific knowledge of human anatomy and biology and had never been exposed to any patient care in a hospital/health center. For seven days, training was given through theoretical lectures and illustrations, including female genital anatomy and demonstration on a human model of how to visualize the cervix and other genitalia, details of the ectoand endocervix and transformation zone, knowledge about epithelial types such as normal squamous and columnar epithelium, metaplastic and acetowhite epithelium. The distinction between normal epithelium and lesions needing referral was highlighted repeatedly on unaided visual inspection and after application of acetic acid and Lugol’s iodine. This was reinforced by means of projecting 175 digital images of different types of cervices depicting normal epithelium, benign lesions, suspicious lesions and

VIA screening for cervical cancer in developing countries: Potential role of the light source

A total of 385 symptomatic patients presenting to the gynaecology and obstetrics outpatient department were screened by two sources of light: the yellow light of the tungsten bulb and the white light of the halogen bulb (100 Watt, 12 Volt), fitted with KODAK 80B filter and diffuser in an instrument called a ‘Magnivisualizer’® (developed by our Institute). Colposcopic examination was the gold standard for visualisation of the cervix. This study clearly brings out the significance of visual examination of the cervix using white light; as, in addition to having perfect correlation with colposcopy (0.86 for white vs 0.53 for yellow light), white light enables us to select the correct site of biopsy. Most of the rural clinics use torch or ordinary tungsten bulb, thus missing many significant lesions. In the light of our research findings, we strongly recommend the use of white light (complete spectrum of light) for screening purposes.

Impacts of TNF-LTA SNPs/Haplotypes and Lifestyle Factors on Oral Carcinoma in an Indian Population

Background and ObjectivesTo investigate a potential association between single-nucleotide polymorphisms (SNPs) and xa0haplotypes at the TNFA-LTA locus and the development of oral cancer in an Indian population.Materials and MethodsIn this study, 150 oral precancer/cancer samples (50 precancer and 100 cancer), along with an equal number of control samples, were genotyped. Six SNPs at the TNF-LTA locus (i.e., −238G/A, −308G/A, −857C/T, −863C/A, −1031T/C, and +252A/G) were analyzed by use of a polymerase chain reaction–restriction fragment length polymorphism method, the assay was validated by sequencing 10 % of samples.ResultsThe allelic frequencies of TNFA and LTA SNPs were found to be significantly associated with the risk of oral cancer and precancerous lesions in comparison with controls (P < 0.0003). Further haplotypic analysis showed that two haplotypes (ATCTGG and ACACGG) served as risk haplotypes for oral cancer. These haplotypes were also found to be significantly and positively associated with lifestyle habits (tobacco chewing Pxa0=xa00.04, odds ratio [OR] 3.4) and socioeconomic status (Pxa0=xa00.01, ORxa03.4). We noticed an increased percentage of risk haplotypes correlating with the aggressiveness of oral cancer. The percentages of risk haplotypes were found to be threefold higher in precancer and fourfold higher in advanced stages of oral cancer in comparison with controls.ConclusionFive SNPs at the TNF-LTA locus (i.e., −308G>A, −857C>T, −863C>A, −1031T>C, and +252A>G) were found to be associated with the development of oral cancer. Two haplotypes (ATCTGG and ACACGG) emerged as major risk haplotypes for oral carcinoma progression and were also found to be associated with lifestyle factors and clinical aggressiveness. These findings make the TNF-LTA locus a suitable candidate for a future biomarker, which may be used either for early detection or for helping to improve treatment efficacy and effectiveness.

AV Magnivisualizer: a low-cost screening technology for early detection of precancerous and early cancerous lesions of the uterine cervix

Cervical cancer is a leading malignancy among women in developing countries. Screening based on visual techniques, including visual inspection (VI), VI with acetic acid (VIA) and VIA under magnification (VIAM), has been tested in different research settings and found to be useful. In the field settings of primary health centres, the only available light source is generally a tungsten bulb emitting yellow light attached to a torch or examination light. This type of light has a masking effect on the lesions in a pinkish mucosal background. Thus, an ideal light source with certain magnification is a highly desirable requirement for VI of the cervix for early detection of early and precancerous lesions. A portable, user-friendly, low-cost device (AV Magnivisualizer), which has a complete spectrum of visible light (white light) and interchangeable magnification, was developed by the authors. This instrument showed better sensitivity to detect significant precancerous lesions of the cervix compared with VIA (83% vs 54%) without losing any specificity. Studies confirmed that the AV Magnivisualizer may replace a colposcope in settings where colposcopy facility may not exist. After studying the potential utilisation and usefulness of its ever-evolving role in screening and evaluation at a very low cost (approximately US

Clinical determinants and smear characteristics of unsatisfactory conventional cervicovaginal smears.

160 per piece), the Government of India launched this instrument for widespread use. The Indian Council of Medical Research has recently completed the agreement for commercial production of the equipment. This article elaborates the development of the device and validation studies on this equipment in various settings.