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

BACKGROUND AND OBJECTIVES: To investigate a potential association between single-nucleotide polymorphisms (SNPs) and  haplotypes at the TNFA-LTA locus and the development of oral cancer in an Indian population. MATERIALS AND METHODS: In 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. RESULTS: The 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 P = 0.04, odds ratio [OR] 3.4) and socioeconomic status (P = 0.01, OR 3.4). 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. CONCLUSION: Five 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.

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.

Share of tobacco related cancers: gender and time gaps-Indian scenario.

INTRODUCTION: Cancer is one of the leading causes of mortality in Indian population with control approach of varied kind which the health system of the country needs to prioritize. The tobacco related cancer which account for major share of all the cancers could be largely controlled through primary prevention a strategy effective in terms of resources hence take priority in terms of cancer control activities. It would be worthwhile to study the cancer of sites and relative magnitude of the cancers which are tobacco related and are amenable for prevention. MATERIALS AND METHODS: The age specific cancer incidence rates of cancer as available from the consolidated reports of the National Cancer Registry Program of Indian Council of Medical Research for the years 1990-96 an 2001-04 were utilized for computing proportion of tobacco related cancers which included population based cancer registries at Bangalore, Bhopal, Barshi a rural registry in Maharashtra, Chennai, Delhi and Mumbai. As defined cancer of the sites oral cavity, lip, tongue, oropharynx, hypopharnx, pharynx, oesophagus, larynx, lung, urinary bladder were considered as tobacco related cancers. The statistical evaluation of proportion of tobacco related cancers between two time periods under consideration was carried out by proportion test. RESULTS: There was a significant decline of proportion of tobacco related cancers from 1990-96 to 2003 for all the registries except Bhopal where around 50% of the total cancers attributed to tobacco habits for the two time periods under consideration. The Barshi also reported a decline but was not statistically significant. In females the proportion of tobacco related cancers ranged between 17% in Bangalore 10% in Delhi for the two time periods under review. All the registries showed significant decline in proportion of tobacco related cancers for the periods under consideration, except Delhi and Bhopal, while rural registry at Barshi revealed an increase of 3.3 %. The gender difference of the proportion of tobacco related cancers ranges between 19.8% to 34% during the period 1990-96, while it was 18.5% to 35% for the period 2001-03. While examining the difference between gender gap between the two time periods, the results from Mumbai registry revealed significant decline.

Performance of a low cost magnifying device, Magnivisualizer, versus colposcope for detection of pre-cancer and cancerous lesions of uterine cervix.

OBJECTIVE: To assess the performance of a low cost magnifying device (Magnivisualizer) compared to a standard optical colposcope for detection of precancerous and cancerous lesions of the uterine cervix. METHODS: A total of 659 consecutive symptomatic women attending a gynecologic outpatient clinic underwent unaided visual inspection followed by cytology, visual inspection of the cervix using 5% acetic acid (VIA), and VIA under magnification (VIAM) with the Magnivisualizer. All women, independently of test results, were referred for colposcopic examination. Colposcopic-directed biopsies were obtained from all positive lesions and compared to positive VIAM cases. RESULTS: The detection rate for VIA positive lesions was 12% (134/659), while it was 29% for VIAM positive lesions (191/659). The sensitivities of detection of cervical intraepithelial neoplasia (CIN) 2 and higher lesions were 61.7% for VIA, 88.3% for VIAM, and 86.7% for colposcopy, with a specificity of 58.5% for VIA, 55.8% for VIAM, and 90.4% for colposcopy. The performance of colposcopy and VIAM was moderate (κ, 0.48; 95% confidence interval [CI], 0.41 to 0.54) for detection of CIN 1 and higher lesions and excellent (κ, 0.87; 95% CI, 0.82 to 0.94) for detection of CIN 2 and higher lesions. CONCLUSION: In low resource settings, where colposcopic facilities are not available at the community level, a simple low-cost, handheld Magnivisualizer can be considered a valid option for detection of cervical precancerous and cancerous lesions. However, it cannot replace traditional colposcopy because it has a low specificity that results in many unnecessary biopsies.

Genetic polymorphism of glutathione S-transferase P1 (GSTP1) in Delhi population and comparison with other global populations.

Glutathione S-transferases (GSTs) belong to a super family of phase II detoxification enzymes, which play an important role in protecting cells from damage caused by endogenous and exogenous compounds by conjugating reactive intermediates with glutathione to produce less reactive water-soluble compounds. In the present study, we determined the frequencies of two polymorphisms in exon 5 and exon 6 of GSTP1 gene in 500 normal individuals from Delhi. GSTP1 polymorphism was analysed by PCR-RFLP using amplification refractory mutation system (ARMS) assay. Two polymorphic sites in GSTP1 (Ile105 â†’ Val105; Ala114 â†’ Val114) have been analysed simultaneously, which results in four alleles: GSTP1*A (wild-type Ile105; Ala114), GSTP1*B (Val105; Ala114), GSTP1*C (Val105; Val114) and GSTP1*D (Ile105; Val114). The GSTP1 allele frequency in Delhi population was 0.663, 0.248, 0.069, and 0.020 for GSTP1*A, GSTP1*B, GSTP1*C, and GSTP1*D respectively. The frequency of Ile105 and Val105 allele was 0.683 and 0.317 respectively and it was calculated for the purpose of comparison with published data where all the four alleles were not analysed. GSTP1 alleles from Delhi population were compared with reported frequencies from all over India, and from other ethnic groups worldwide. This study would provide a basic database for future genetic studies.

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.

Role of vault cytology in follow-up of hysterectomized women: results and inferences from a low resource setting.

The study was undertaken to assess the utility of cervico-vaginal/vault cytology in the follow-up of women treated for cervical cancer and benign gynecological conditions. Records of 3,523 cervico-vaginal smears from 2,658 women who underwent hysterectomy and/or radiotherapy or chemotherapy, over a 10-year period were retrieved. Data was collected on type of treatment received, indication for hysterectomy, age of patient, presenting symptoms, stage of tumor, interval since treatment, cytology and biopsy results. The results of cytology versus other parameters were analyzed separately for women treated for cervical cancer and those hysterectomized for benign indications. Malignant cells were detected in 141/1949 (7.2%) follow-up smears from treated cervical cancer cases (140 recurrences and 1 VAIN). Around 92% of recurrences of cervical cancer were detected with in 2 years of follow-up and 75% of these women were symptomatic. Cytology first alerted the clinicians to a recurrence in a quarter of cases. On the other hand, VAIN was detected in 5/1079 (0.46%) vault smears from 997 women hysterectomized for benign gynecologic disease. All these women were asymptomatic and majority (80%) were detected in follow-up smears performed between 3 and 10 years. Vault cytology is an accurate tool to detect local recurrences/VAIN in women treated for cervical cancer or benign gynecological conditions. It may even first alert the clinicians to a possibility of recurrence. However, due to extremely low prevalence of VAIN/vaginal cancer, it seems unwarranted in women hysterectomized for benign indications, especially in resource constrained settings.

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.

New insights into hepatitis C virus infection in the tribal-dominant part of Northeast India.

Northeast India is known for the demographic heterogeneity of its tribal population, but there is no information about hepatitis C virus infection and associated risk factors. Anti-HCV was measured, HCV-RNA was detected based on the 5' UTR-core region, and genotyping was done by direct sequencing of the NS5b region. Antibodies to HCV were found in 13.7 % of the samples tested (96 out of 700), while HCV-RNA was positive in 73 % of the samples (70 out of 96) and in 5 out of 385 cases of occult HCV infection. Genotypes 1 to 4 were found respectively in 14.6, 7.3, 20, 30.8 %, and genotype 6 in 13.6 %, of the 75 HCV isolates. In acute viral hepatitis (AVH), the most prevalent genotype was 2a (28.6 %), while it was 4a (28 %) in chronic hepatitis C (CHC) and 29.4 % in cirrhosis. Males were more prone than females to HCV infection, and the highest numbers of cases of HCV infection were recorded in the age group of 40-49 years. The major risk factors were intravenous drug abuse (IVDU) (34.6 %), multiple sexual partners (20 %) and contact with professional barbers (38.6 %). The seroprevalence of HCV in Northeast India is higher than in the rest of India. This study highlights the fact that geographical variations occur with respect to HCV genotypes, which could influence the course and progress of different type of liver diseases seen in India.

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.

Human papillomavirus infection (HPV) & screening strategies for cervical cancer.

The incidence of cervical cancer is declining slowly necessitating concerted and organized control measures. Control through primary prevention has become a distinct reality though a prophylactic vaccine, which may take quite some time for its widespread use. Thus control of cervical cancer through secondary preventive measures is the only viable solution now. While high quality cytology screening may not be feasible for widescale implementation in developing countries because of lack of necessary infrastructure, quality control and poor sensitivity of cytology, alternative screening modalities such as visual screening techniques and HPV-DNA can be explored. Some technical and feasibility aspects of these three modalities are discussed.

Outcome of "Atypical squamous cells" in a cervical cytology screening program: implications for follow up in resource limited settings.

(1) To study the incidence and outcome of "Atypical squamous cells (ASC)" diagnosis in a hospital based cytology screening programme. (2) To work out a feasible strategy for follow up of Atypical squamous cells-undetermined significance (ASC-US) and Atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H) in resource limited settings. A total of 29,475 women were screened cytologically through Pap tests. The epithelial cell abnormalities (ECA) detected on screening were reviewed by the cytopathologists and classified according to Bethesda 2001 system. The women with ASC-US reports were followed up by two repeat cytology tests at 3 and 6 months of the initial visit. The persistent ASC-US cases or the cases which revealed squamous intraepithelial lesion (SIL) on follow up smears; as well as all ASC-H and above cases were referred for coloposcopic evaluation. ASC diagnosis comprised 3.6% of all reports. These were qualified as ASC-US (3.36%) and ASC-H (0.22%). On follow up, only 7 CIN 2 or worse (3.2%) lesions were detected on 218 biopsies in ASC-US category while in ASC-H qualifier 16 CIN 2 and above lesions (30.8%) were picked up on 52 colposcopic biopsies. The difference between ASC-US and ASC-H categories for a CIN 2 or worse outcome was highly significant (P < 0.001). ASC-H qualifier has a high likelihood for an ominous histological outcome and warrants an immediate colposcopic evaluation. On the other hand, ASC-US cases can be managed conservatively by repeat cytology tests at regular intervals without a significant risk of missing a high grade lesion. Diligent screening of cervical smears can judiciously downgrade some cases overcalled as ASC because of inflammatory atypia and thereby reduce referrals in geographic settings with high prevalence of reproductive tract infections. High risk HPV (HR HPV) testing may be a useful adjunct to further reduce referrals by selecting the women who require colposcopic evaluation.

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.

Sensitivity of the Pap test in detecting high grade lesions: what should be the acceptable cytologic threshold for colposcopic referral?

OBJECTIVE: To devise an optimal cytology threshold for colposcopy referral in resource-limited settings. STUDY DESIGN: Four hundred seventy-two symptomatic women 20-60 years old were screened by both cytology and colposcopy. Onsite biopsy was taken if lesions grade 1 or above were detected on colposcopy. Women found to have cervical intraepithelial neoplasia (CIN) 2 and above lesions on histopathology were stratified according to their cytologic diagnosis (atypical squamous cells of undetermined significance [ASCUS]+ threshold, low grade squamous intraepithelial lesion [LSIL]+ threshold, and high grade squamous intraepithelial lesion [HSIL]+ threshold). The comparative sensitivity, specificity and predictive values in each group were calculated, taking biopsy as the gold standard. RESULTS: The sensitivity of LSIL + cytology to detect CIN 2+ lesions was 91.5% (referral load, 30.7%). While the sensitivity of ASCUS+ cytology threshold was almost the same (92.3%), the referral load was much higher (42.2%). With HSIL+ cytology threshold, though the referral load was reduced substantially (21.9%), the sensitivity also decreased, to 81.5%. CONCLUSION: The results indicate that in order to achieve high sensitivity, the LSIL cytology threshold appears to be optimum for colposcopic referrals.

Eliminating the diagnosis atypical squamous cells of undetermined significance: impact on the accuracy of the Papanicolaou test.

OBJECTIVE: To assess eliminating the diagnosis "atypical squamous cells of undetermined significance" (ASCUS) from the Bethesda System for Reporting Cervical/Vaginal Cytological Diagnoses and analyze its impact on the sensitivity and positive predictive value of Pap smears. STUDY DESIGN: A total of 166 previously diagnosed ASCUS cases with follow-up biopsy results available were prospectively downgraded to within normal limits/benign cellular changes or upgraded to specific squamous intraepithelial lesions (SILs) or the malignant category. These review cytodiagnoses were compared with the histologic outcome. The impact on the sensitivity and positive predictive value of Pap smears was also assessed. RESULTS: Though there was a decrease in the sensitivity of the Pap smear from 100% to 76.3% for SIL overall and from 100% to 80% for high grade SIL (HSIL) alone, there was an improvement in the positive predictive value of diagnosing SIL from 46% to 85% and from 6% to 15% for HSIL alone. CONCLUSION: The ASCUS diagnosis can be minimized to a great extent, if not eliminated completely. The "ASCUS-favor reactive" group can be eliminated, while the diagnoses "ASCUS favor SIL" and "ASCUS-not otherwise specified" should be used sparingly.