Comparison of acceptability & efficacy of thermal ablation (thermocoagulation) & cryotherapy in VIA positive cervical lesions: A pilot study.

BACKGROUND OBJECTIVES: The World Health Organization (WHO) has endorsed thermal ablation (thermocoagulation) as an efficient and safe modality for treatment of cervical pre-cancer lesions. More evidence is being looked up by WHO through rigorous studies for health delivery models using screen-and-treat strategies incorporating thermal ablation and studies comparing it against the conventional standard modality cryotherapy. The objective of this study was to assess the acceptability of thermal ablation both among the providers and clients and compare the same with cryotherapy. METHODS: A randomized control trial was conducted for one year from September 2019 to October 2020 after obtaining ethics approval. Computer-generated random number table was used for randomization, and eligible candidates were divided into two groups following informed consent. Women with visual inspection with acetic acid (VIA) positive cervical lesions in Group A received cryotherapy and Group B received thermal ablation. After the procedure, the acceptability of the provider and the client were assessed using the International Agency for Research on Cancer-validated questionnaire for both the procedures. Immediate side effects and problems at six weeks and at six months were assessed as well. Efficacy was decided by the absence of VIA positivity at six months. RESULTS: The overall VIA positivity in this study was 11.8 per cent. Thermal ablation (thermocoagulation) had better provision and client acceptability than cryotherapy (significant difference). The efficacy of thermal ablation was 97.6 per cent, while, it was 92 per cent for cryotherapy (not significant). INTERPRETATION CONCLUSIONS: In the context of screen-and-treat programme in settings such as India, thermal ablation appears to be a better method of treatment than cryotherapy for cervical pre-cancerous lesions particularly in terms of better provision and client acceptability.

Diagnostic Accuracy of Plasma Cystatin C and Renal Resistive Index for Acute Kidney Injury in Critically Ill Patients: A Prospective Observational Study.

Background: Acute kidney injury (AKI) is a quite common problem in critically ill patients. Serum cystatin C has emerged as a marker of AKI. This study was aimed to evaluate the diagnostic ability of serum Cystatin-C and Renal Resistive Index in prediction of AKI among critically ill patients. Methodology: This prospective observational study was carried out in the department of Medicine, over a period of one year. After informed consent and ethical clearance total 120 critically ill patients suffering from sepsis were enrolled, out of which 70 patients developed AKI while 50 did not develop AKI during treatment in Intensive care unit (ICU). Serum cystatin C was measured on day 1 by particle-enhanced immune nephelometric assay, Renal resistive index (RRI) calculated by ratio of the velocities of arterial perfusion throughout the cardiac phase and glomerular filtration rate was measured on days 1, 3, and 7 respectively. Results: S. cystatin C value was significantly higher(>3times) in AKI patients (14.07±4.8 mcg/ml) as compared to those who did not develop AKI (4.28±3.27 mcg/ml) (p<0.001). After ROC analysis it was found that day1, S. cystatin C, at cut off value of ≥9.29 mcg/ml had diagnostic accuracy 90% with sensitivity 91%, specificity89% and PPV 95.5%. While RRI value on day 7, at cut-off value of ≥0.72, had diagnostic accuracy 98%, sensitivity (98.6%) and specificity (96.7%) for AKI with 98.6% PPV, 96.7% NPV. Conclusion: Serum cystatin C appears to be a promising bio- markers for early diagnosis of AKI in critically ill patients. Whereas, RRI although non-invasive had good diagnostic accuracy but it diagnosed AKI after few days thus diagnosis of kidney injury delayed.

Placental Growth Factor in First Trimester of Pregnancy for Prediction of Maternal and Perinatal Adverse Outcomes.

Purpose of the study: Placental growth factor (PLGF) is an angiogenic factor in pregnancy. To find out correlation of plasma levels of placental growth factor in first trimester of pregnancy in Indian women who develop maternal and perinatal adverse outcomes was the aim of the study. Methods: A prospective longitudinal noninterventional study was done in the department of Obstetrics and Gynecology after obtaining ethics approval. After enrolling patients in the first trimester (11 weeks to 13 weeks 6 days), a questionnaire was filled for demographic characteristics. Uterine artery doppler was done for every patient and blood sample (5 ml) was taken by venu puncture of median cubital vein. Serum levels of PLGF were measured by enzyme linked immunosorbent assay using Thermo Scientific Pierce Human PLGF kit (Thermo Fisher Scientific, Inc., Waltham, MA, USA). Patients were followed for their whole antenatal period and delivery outcomes. Results: Incidence of preeclampsia in our study was 9.3% (15/161) and fetal growth restriction (FGR) was 19.8% (32/161). Neither BMI nor nulliparity was found to have statistically significant correlation with development of preeclampsia. However, history of preeclampsia was found to be significant risk factor for prediction of preeclampsia (p value < 0.04). Plasma levels of PLGF were significantly lower in preeclampsia and FGR group and this difference was statistically significant (p value < 0.04). 7.5% still born occurred in complicated group and 10% needed NNU/NICU admission in this group. Conclusion: Measuring PLGF levels in first trimester of pregnancy can help in prediction of preeclampsia and FGR.

Single step "See and Treat" strategy might be replacing the "conventional three step strategy" in management of preinvasive cervical lesions at tertiary center: A North Indian study.

Introduction: The aim of this study was to compare overtreatment rates of see and treat colposcopy-based single step protocol with cytology and colposcopy-guided biopsy-based conventional three-step protocol using loop electrosurgical excision procedure (LEEP) for treatment of preinvasive lesions of cervix. Materials and Methods: Prospective interventional study was carried out over a period of 1 year. Recruitment of cases was done from the 664 diagnostic colposcopies performed for various gynecological indications. Among 496 colposcopies performed exclusively for unhealthy cervix on per speculum examination, 74 women had high-grade colposcopy (Swede score ≥5). Subsequently, 50 women were enrolled under the see and treat arm, arm 1 and underwent LEEP. In study arm 2, conventional three-step strategy, concurrently 22 women with abnormal cytology. ≥ Atypical squamous cells of undetermined significance and unhealthy cervix were enrolled for colposcopy and if indicated, guided biopsy was obtained and tissue was sent for histopathology. Only 12 such women having HPE reports of cervical intraepithelial neoplasia (CIN) 2 or 3 were subjected to LEEP. Overtreatment was defined as CIN 1 or less on final LEEP tissue histopathology. Results: The overtreatment rate in See and Treat protocol was 44% when colposcopy Swede score cutoff was considered 5, which fell down to 0% when Swede score cutoff was taken 7. Conventional three step protocol had an overtreatment rate of 8.3%. Incidentally diagnosed high-grade CIN or invasive cancer was found in 24%. Discrepancy between biopsy tissue and LEEP tissue histopathology was 50% in conventional arm. Conclusion: Women with unhealthy cervix having high-grade colposcopy (Swede score ≥7) can be directly subjected to LEEP without waiting for results of any initial screening modality. Advantages include minimal over treatment coupled with reduced patient visits and interventions.

ROC-Analysis Derived Immunohistochemical P53 Cut-Off Scores as an Adjunct to Routine Histopathology for Better Diagnostic Compartmentalisation of Cervical Lesions.

Objective: The aim of this study was to evaluate the predictive value of Immunohistochemical p53 cut-off scores as an adjunct to routine histopathology for better diagnosis of cervical lesions. Materials and Methods: Prospective study carried out for 1 year. After ethical approval and informed consent, a total of 100 cervical tissue samples were analyzed; chronic cervicitis (CC)-15, cervical intraepithelial neoplasia (CIN)-40, and squamous cell carcinoma cervix (SCC)-45 (FIGO 2018 clinical staging). After routine processing of tissue specimen, hematoxylin and eosin (HE) staining was done. Grading of cervical precancerous lesions (CIN) was done as per World Health Organisation criteria as CIN 1,2 or 3. Broder's grading was assigned for every SCC sample. Results: Mean p53 scores of CC, CIN, and SCC cases were 0.0, 1.70, and 4.38, respectively, CIN 1, 2, and 3 were 1.07, 1.63, and 2.22, respectively. SCC was differentiated from CIN3 with p53 ≥4.5 as predictor for SCC, sensitivity and specificity were 57.8% and 88.9%, respectively. Overall diagnostic accuracy of the proposed scoring system for differentiating CC, CIN, and SCC was 61%, while the accuracy of previous methods of interpreting p53 immunoreactivity as immunoscore >2 or arbitrary cut-off of >10% cells with nuclear positivity was only 48%. Conclusion: ROC-derived immunoscore cut-offs can provide the much-needed objectivity and optimal decision thresholds to immunohistochemistry interpretation.

Randomized controlled study for comparison of efficacy and safety between thermocoagulation and cryotherapy in visual inspection with acetic acid positive cervical lesions.

Background: Less literature is available on the performance of thermocoagulation for treatment of premalignant cervical lesions and its comparison with cryotherapy from low- and middle-income countries like India. Materials and Methods: : A prospective randomized controlled study was done in the Department of Obstetrics and Gynecology from August 2018 to September 2019 after obtaining ethical clearance from Institutional Review Board (Reg no: ECR/262/Inst/Up/2013/RR/16) Ref no: 278/Ethics/R. cell-18). A total of 68 women with Visual inspection with acetic acid (VIA) positive cervical lesion were randomized into two groups. Group A was treated with cryotherapy and Group B was treated with thermocoagulation. Estimates of cure, adverse effects or complications were presented as frequencies, percentages, and mean ± standard deviation. Results: Out of 667 patients, 624 patients underwent VIA testing among which 68 were VIA positive (10.89%, 68/624). The efficacy of thermocoagulation was 93.54% and that of cryotherapy was 90.32%. Immediate side effects were significantly lesser in thermocoagulation group (P = 0.008) in comparison to cryotherapy. Conclusion: Thermocoagulation is better treatment modality than cryotherapy for VIA-positive cervical lesions may not be in terms of efficacy but definitely in terms of patient comfort and safety.

Clinical Significance of Circulating Serum Levels of sCD95 and TNF-α in Cytoprotection of Cervical Cancer.

Background: This study correlates the serum levels of sCD95 & TNF-α with a simple cell-based assay to evaluate the capacity of the serum sample to induce apoptosis in Jurkat cells. Interlinking of these parameters can be explored to design a minimum invasive diagnostic strategy for cervical cancer (CC). Methods: Sera samples were assessed to induce apoptosis in Jurkat cells through FACS. Serum levels of sCD95 and TNF-α were measured by ELISA. JNK phosphorylation was evaluated in sera incubated Jurkat cells. Data was scrutinized through statistical analysis. Results: Significantly higher serum levels of sCD95 and lower TNF-α levels were observed in CC patients; their sera samples inhibited induction of apoptosis in Jurkat cells through reduced JNK phosphorylation. Statistical analysis linked these three parameters for the early screening of CC. Conclusion: Distinct sera levels of sCD95 & TNF-α in CC patients showed an anti-apoptotic effect, which can be considered for early detection of CC.

Noninvasive Point-of-Care Nanobiosensing of Cervical Cancer as an Auxiliary to Pap-Smear Test.

A potential cancer antigen (Ag), protein-phosphatase-1-gamma-2 (PP1γ2), with a restricted expression in testis and sperms has been identified as a biomarker specific to cervical cancer (CaCx). Detection of this cancer biomarker antigen (NCB-Ag) in human urine opens up the possibility of noninvasive detection of CaCx to supplement the dreaded and invasive Pap-smear test. A colorimetric response of an assembly of gold nanoparticles (Au NPs) has been employed for the quantitative, noninvasive, and point-of-care-testing of CaCx in the urine. In order to fabricate the immunosensor, Au NPs of sizes ∼5-20 nm have been chemically modified with a linker, 3,3'-di-thio-di-propionic-acid-di(n-hydroxy-succinimide-ester) (DTSP) to attach the antibody (Ab) specific to the NCB-Ag. Interestingly, the addition of Ag to the composite of Ab-DTSP-Au NPs leads to a significant hypsochromic shift due to a localized surface plasmon resonance phenomenon, which originates from the specific epitope-paratope interaction between the NCB-Ag and Ab-DTSP-Au NPs. The variations in the absorbance and wavelength shift during such attachments of different concentrations of NCB-Ag on the Ab-DTSP-Au NPs composite have been employed as a calibration to identify NCB-Ag in human urine. An in-house prototype has been assembled by integrating a light-emitting diode of a narrow range wavelength in one side of a cuvette in which the reaction has been performed while a sensitive photodetector to the other side to transduce the transmitted signal associated with the loading of NCB-Ag in the Ab-DTSP-Au NPs composite. The proposed immunosensing platform has been tested against other standard proteins to ensure noninterference alongside proving the proof-for-specificity of the NCB detection.

Evaluation of Serum Cystatin C as an Early Biomarker of Acute Kidney Injury in Patients with Acute Pancreatitis.

INTRODUCTION: Acute pancreatitis (AP) is an inflammatory process of pancreas with varying degree of involvement of regional tissues. The aim of this study was to investigate the potential use of serum cystatin C (Cys-C) for the early and accurate diagnosis of acute kidney injury (AKI) in patients of AP. MATERIALS AND METHODS: This was a prospective study conducted in 1 year. Total of 215 cases of AP fulfilling the inclusion criteria were enrolled in this study. Patients suffering from chronic pancreatitis, neoplasm, chronic liver disease, and chronic kidney disease were excluded from the study. Diagnosis of AP was based on the Atlanta classification 2012. All patients were classified into a non-AKI group (n = 152) and an AKI group (n = 38) according to the dynamic changes in serum creatinine levels. Serum Cys-C was measured by particle-enhanced immune nephelometric assay. RESULTS: By univariate logistic regression analysis, body mass index (BMI) (OR = 1.44, 95% CI: 1.23-1.68; p < 0.001), blood urea (OR = 1.15, 95% CI: 1.06-1.23; p < 0.001), Cys-C (OR = 1.04, 95% CI: 1.01-1.07; p < 0.05), serum calcium (OR = 0.59, 95% CI: 0.41-0.86; p < 0.05), and serum lactate dehydrogenase (LDH) (OR = 1.001, 95% CI: 1.0-1.001; p < 0.05) were the significant indicators for AKI in patients with AP. Using multivariate logistic regression analysis, urinary albumin and Cys-C were independent and significant indicators of AKI in patients with AP (OR = 1.026, 95% CI: 1.01-1.07; p < 0.01). Receiver operating characteristic (ROC) curve of serum Cys-C, for AKI in patient with AP could be identified with a sensitivity of 92.06% at specificity of 96.0% [area under the curve (AUC) = 0.96, 95% CI: 0.92-0.98] by baseline serum Cys-C (cutoff value = >32.32 mg/L). CONCLUSION: Increase of baseline serum Cys-C was associated with AKI in patients with AP. HOW TO CITE THIS ARTICLE: Patel ML, Shyam R, Bharti H, Sachan R, Gupta KK, Parihar A. Evaluation of Serum Cystatin C as an Early Biomarker of Acute Kidney Injury in Patients with Acute Pancreatitis. Indian J Crit Care Med 2020;24(9):777-782.

HIV-1 Nef-POTEE; A novel interaction modulates macrophage dissemination via mTORC2 signaling pathway.

AIMS: Human immunodeficiency virus -1 [HIV-1] Nef, localizes in different cellular compartments and modulates several cellular pathways. Nef promotes virus pathogenicity through alteration in cell surface receptor expression, apoptosis, protein trafficking etc. Nef regulates viral pathogenesis through interaction with different host proteins. Thus, molecular mechanisms of pathogenesis could be deciphered by identifying novel Nef interacting proteins. MAIN METHODS: HIV-1 Nef interacting proteins were identified by pull down assay and MALDI-TOF analysis. The interaction was further validated through mammalian two hybrid assay. Functional role of this interaction was identified by immunoprecipitation assay, cell invasion and cell migration studies. Fold Change in mRNA levels of CD163, CD206, CCL17 and CCL18 was analyzed using qPCR. KEY FINDINGS: In current study, C. elegans protein ACT4C and its human homolog POTEE was identified to be interacting with Nef. This interaction activates mTORC2 complex, which in-turn activates AKT and PKC-α. The activation of mTORC2 complex was found to be initiated by the interaction of Nef, mTORC2, Rictor to POTEE. The cellular phenotype and functions affected by Nef-POTEE interaction resulted in significant increase in cell invasion and migration of macrophages (MΦ). SIGNIFICANCE: MΦ is primary target of HIV-1 infection where HIV-1 replicates and polarizes immunosuppressive M2 phenotype. Combine effect of M2 phenotype and Viral-host protein interactions compromise the MΦ associated physiological functions. Infected MΦ dissemination into other system also leads to HIV-1 induced malignancies. Therefore, targeting POTEE-Nef interaction can lead to formulating better therapeutic strategy against HIV-1.

A Study on Cervical Cancer Screening Using Pap Smear Test and Clinical Correlation.

OBJECTIVE: The objective of the study is to evaluate the use of the Pap smear screening method for detection of precancerous lesions. METHODS: All women who visited the outpatient gynecology clinic of the Department of Obstetrics and Gynaecology at King Georges Medical University, Lucknow, UP, India, over 1 year for different clinical problems were recruited for the study. A total of 1650 women who were sexually active and over 21 years of age were enrolled in the study. A clinical examination, an examination per speculum, and a vaginal examination were performed and a history taken for all women. A Pap smear was used for all women to screen for cervical cancer. The smear was obtained using an Ayre spatula and spread over a marked glass slide, which was placed in 95% ethyl alcohol and sent to the Department of Pathology for cytopathological examination. All data were recorded using a predetermined pro forma. Women who had visible malignant cervical lesions were excluded from the study. RESULTS: Most women were in the age range of 30-50 years and multiparous. Vaginal discharge was the most common complaint, occurring in 36.96% of the women. An irregular menstrual cycle was the complaint of 12.78% and abdominal pain of 25.63% of women, while 15.15% were asymptomatic. The Pap smear test of 93.57% of the women was adequately taken, while 6.42% of the individuals had an inadequate sample. The test was negative for malignancy in 48.84%, and 42.66% had infection or inflammation. Atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL) were detected in 2.90%, 5.09%, and 0.48%, respectively. Women with Pap tests positive for ASCUS, LSIL, and HSIL underwent a colposcopy and guided biopsy. CONCLUSIONS: Women with an abnormal Pap test should undergo a colposcopy, and those with abnormal colposcopy findings should be advised to undergo a biopsy. A Pap smear is simple, noninvasive, cost-effective, and easy to perform for detection of precancerous lesions in a gynecological patient.

Complete axial torsion of pregnant uterus with leiomyoma.

Uterine torsion is defined as a rotation of the uterus of more than 45° along its long axis. It is a rare complication during pregnancy; a common cause of torsion can be uterine myoma. Here we describe the case of a 27-year-old G2P1+0 woman at 15 weeks 3 day pregnancy, who presented to our outpatient department as a case of acute abdomen, in a state of shock. Clinical findings did not correlate with investigation. On lapratomy she was diagnosed as a case of complete axial torsion of pregnant uterus with fundal myoma with massive abruption. Early diagnosis and timely intervention would help in improving both maternal and fetal outcome.

Cervical tuberculosis masquerading as cancer cervix: a report of three cases.

Tuberculosis is still frequently observed in third world countries like Africa and Asia. Here we report three cases of genital tuberculosis with variable presentations. First case was a lady of reproductive age group who presented with polymenorrhea and post-coital bleeding with unhealthy cervix. Histopathology of cervical tissue revealed tubercular cervicitis. Second and third cases presented with different complaints like discharge per vaginum, post-coital bleeding and pain in lower abdomen with growth over the cervix. Cervical biopsy was inconclusive of tuberculosis but endometrial tissue sampling for TB PCR was positive. This shows that newer diagnostic marker test can help us to detect secondary genital tuberculosis.

A protocol for stripping and reprobing of Western blots originally developed with colorimetric substrate TMB.

Western blotting is a widely used analytical technique for detection of specific protein(s) in a given sample of tissue/cell homogenate or extract. Both chemiluminescence (CL) and colorimetric detections can be used for imaging Western blots. Colorimetric substrates offer background free, sensitive, and clean imaging results directly on the blotted membrane and provides more accurate profile with respect to prestained marker. However, blots stained with colorimetric substrates cannot be reused since no stripping protocols have been reported for such blots, thus limiting their reuse for detection of another protein. In the present study, for the first time, we report a novel method of stripping Western blots developed with the colorimetric substrate TMB for detection of a low-abundant protein and reprobing of these blots after stripping for detection of a more abundant protein through CL procedure. The stripping procedure utilizes a stripping buffer consisting of ß-mercaptoethanol, SDS, and Tris-HCl and a washing buffer consisting of PBS added with 0.1% Tween-20 involves a series of steps and facilitates accurate detection of the second protein (i.e., more abundant protein) in the stripped blot through CL. The protocol is reproducible and facilitates saving of precious clinical samples, in addition to saving cost and time as compared to the existing procedures.

Genital tuberculosis with variable presentation: a series of three cases.

Tuberculosis (TB) is still frequently observed in third-world countries like Africa and Asia. Here we report three cases of genital TB with variable presentation. First case was a lady of reproductive age group who presented with polymenorrhagia and postcoital bleeding with unhealthy cervix. Histopathology of cervical tissue revealed tubercular cervicitis. Second and third cases presented with different complaints like discharge per vaginum, postcoital bleeding and pain in lower abdomen with growth over the cervix. Cervical biopsy was inconclusive of TB but endometrial tissue sampling for TB PCR was positive. This shows that newer diagnostic marker test can help us to detect secondary genital TB.

Association of TNFA (-308G>A) and IL-10 (-819C>T) promoter polymorphisms with risk of cervical cancer.

Etiology of cervical cancer is associated with excessive inflammation mediated tumorigenesis. Pro and anti-inflammatory cytokines (tumor necrosis factor alpha, TNFA and interleukin, IL-10) are involved in fighting against the tumorigenesis. Therefore, the present study was designed to evaluate the association of TNFA (-308G>A) and IL-10 (-819C>T) gene polymorphism with risk of cervical cancer. One hundred fifty histopathologically confirmed patients with cervical cancer and 162 age, ethnically-matched cervical cytology negative healthy controls were genotyped for TNFA (-308 G>A) and IL-10 (-819 C>T) polymorphisms using PCR-RFLP. Individuals with combination of TNFA -308GA+AA genotype and A allele were at elevated risk of cervical cancer (odds ratio (OR) = 2.24; P = 0.018 and OR, 2.05; P = 0.012). Frequency of IL-10 -819CT+TT genotype combination and T allele was slightly higher in cases as compared with controls but difference was not significant (OR = 1.52; P = 0.069 and OR = 1.38; P = 0.051). In association of genotypes with clinical characteristics, presence of TNFA -308GA+AA genotype conferred high risk for the stages (IB) (OR = 2.86, P = 0.039) and stages (III) (OR = 2.52; P = 0.015) of cervical cancer. In contrast, IL-10 -819TT genotype was not associated with higher risk of clinical characteristics of cervical cancer. In conclusion, individuals with TNFA -308*A allele carriers were at significantly higher risk of cervical cancer particularly early (IB) and advanced stages (III). However, IL-10 (-819C>T) polymorphism was not associated with risk of cervical cancer.

CCR5-Delta32 polymorphism and susceptibility to cervical cancer: association with early stage of cervical cancer.

Inflammation plays a major role in the pathogenesis of cervical cancer. Chemokines are involved in inflammation, cancer, and infectious diseases. Therefore, we evaluated the association of the chemokine receptor gene polymorphism CCR5 Delta32 with risk of cervical cancer. A total of 150 histopathologically confirmed patients with cervical cancer and 162 age and ethnically matched cervical cytology negative healthy controls were genotyped for CCR5 Delta32 polymorphisms using PCR. Association of CCR5 Delta32 genotypes with risk of cervical cancer, clinical stages, and tobacco exposure was analyzed using chi-square statistical tests. The frequency of the mutant allele CCR5 Delta32 was higher in patients with cervical carcinoma (2.3%) but there was no statistically significant difference (OR = 1.51; p = 0.685;). Association of CCR5 genotypes with clinical phenotypes showed significant risk with stage IB patients due to CCR5+/Delta32 genotype (OR = 4.43; p = 0.021). Furthermore, patients with CCR5+/Delta32 genotype and tobacco usage were at risk of cervical cancer (OR = 1.73, 95% CI = 0.27-1.28). In summary, CCR5 heterozygous genotype (+/Delta32) may significantly influence the early stage of cervical cancer development. However, the cervical cancer risk due to tobacco usage was not significantly modulated after interaction with CCR5+/Delta32 genotype.

Association of GSTM1, GSTT1, and GSTM3 gene polymorphisms and susceptibility to cervical cancer in a North Indian population.

OBJECTIVE: The objective of the study was to evaluate the influence of genetic polymorphisms of GSTM1, GSTT1, and GSTM3 on the susceptibility of cervical cancer. STUDY DESIGN: Blood samples from 150 women with biopsy-confirmed cervical cancer and 168 healthy controls were analyzed by multiplex polymerase chain reaction (PCR) to detect the presence or absence of GSTM1 and GSTT1. Insertion/deletion polymorphism in intron 6 of GSTM3 was determined by PCR. RESULTS: The frequencies of homozygous GSTM1 null and GSTT1 null genotypes were found to be significantly higher in cancer patients as compared with healthy controls (P = .009, odds ratio [OR] 1.52, 95% confidence interval [CI], 1.1 to 2.0 and P = .0004, OR 2.4, 95% CI: 1.4 to 4.0, respectively). The AB genotype of GSTM3 also conferred higher risk of cancer (P = .053, OR 1.64, 95% CI, 1.0 to 2.6). However, no significant association of at-risk genotypes was observed with any stages of cervical cancer. Interactions among GSTM1 null, GSTT1 null, and AB genotype of GSTM3 resulted in additive predictive risks of cervical cancer. In case-only analysis, carriers of the AA genotype of GSTM3 among tobacco users were at elevated risk of cervical cancer (P = .024, OR 2.1, 95% CI, 1.0 to 4.1) as compared with AB and BB genotypes. CONCLUSION: GSTM1 null, GSTT1 null, and GSTM3*AB genotypes may confer higher susceptibility to cervical cancer and cancer risk because at-risk genotypes are additive. Tobacco usage by carriers of GSTM3*AA has enhanced the risk of cervical cancer as compared with nonusers.