• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5519-5525
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• 2013

Background: Cervical cancer is the second most common cancer in Thai women after breast cancer. Currently, the Papanicolaou (Pap) smear is the recommended procedure for cervical cancer screening in Thailand, but only a relatively small percentage of women follow this screening program. An alternative method to detect HPV genotypes associated with cervical cancer is self-sampling of urine, which is a more widely accepted method. Our study aimed to evaluate the prevalence of HPV in Thai women using urine and cervical swabs and prevalence of HPV in Thai men using urine samples. Materials and Methods: Tumorigenic HPV detection was accomplished by electrochemical DNA chip and PCR/direct sequencing. In addition to HPV prevalence, we report the concordance between different methods and sample types. One-hundred and sixteen women and 100 men were recruited. Histological examination revealed normal cytology in 52 women, atypical squamous cells of undetermined significance (ASCUS) in 9, low-grade squamous intraepithelial lesions (LSIL) in 24, and high-grade squamous intraepithelial lesions (HSIL) in 31. One-hundred men were classified as heterosexuals (n=45) and homosexuals (n=55). Results: The most prevalent HPV genotype in our study was HPV16. The HPV detection rate was generally lower in urine samples compared with cervical samples. Overall, there was good agreement for the detection of carcinogenic HPV from female cervical samples between the DNA chip and PCR/sequencing, with 88.8% total agreement and a kappa value of 0.76. In male urine samples, the level of agreement was higher in heterosexuals compared with homosexuals. Conclusions: Further improvement is required to increase an overall yield of HPV DNA detection in urine samples before clinical application of a urine-based HPV screening program. The electrochemical DNA chip test is a promising technique for carcinogenic HPV detection.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6429-6438
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• 2015

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 ${\leq}35$ 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.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.341-346
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• 2013

The risk of cervical cancer development in women infected with HPV varies in relation to the individual host's genetic makeup. Many studies on polymorphisms as genetic factors have been aimed at analyzing associations with cervical cancer. In this study, single nucleotide polymorphisms (SNPs) in 3 genes were investigated in relation to cervical cancer progression in HPV16 infected women with lesions. Two thousand cervical specimens were typed by PCR sequencing methods for TP53 (rs1042522), p16 (rs11515 and rs3088440) and NQO1 (rs1800566). Ninety two HPV16 positive cases and thirty two normal cases were randomly selected. Analysis of TP53 (rs1042522) showed a significantly higher frequency in cancer samples (OR=1.22, 95%CI=1.004-1.481, p-value=0.016) while differences in frequency were not significant within each group (p-value=0.070). The genotype distributions of p16 (rs11515 and rs3088440) and NQO1 (rs1800566) did not show any significantly higher frequency in cancer samples (p-value=0.106, 0.675 and 0.132, respectively) or within each group (p-value=0.347, 0.939 and 0.111, respectively). The results indicated that the polymorphism in TP53 (rs1042522) might be associated with risk of cervical cancer development in HPV16 infected women. Further studies of possible mechanisms of influence on cervical cancer development would be useful to manage HPV infected patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10143-10149
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• 2015

Background and Aim: No firm evidence of HPV infection in esophageal cancer has been established to date. The aim of this meta-analysis was to investigate the prevalence of HPV 16 in esophageal cancer in China, which had a high burden of the disease. Materials and Methods: Studies on HPV infection and esophageal cancer were identified and a random-effects model was used to pool the summary prevalence and corresponding 95% confidence intervals (CIs). Results: A total of 3,429 esophageal cancer cases were evaluated from 26 eligible studies in this meta-analysis. The summary estimate for HPV16 prevalence was 0.381 (95% CI: 0.283, 0.479). The prevalence varied by geographical areas of the study, publication year, HPV detection method and types of specimen. In sensitivity analysis, HPV 16 prevalence ranged from 0.368 (95% CI: 0.276, 0.460) to 0.397 (95% CI: 0.286, 0.508). Conclusions: The results indicate a relatively high level of HPV 16 prevalence in esophageal cancer among Chinese population, although there was variation between different variables. Further studies are needed to elucidate the role of HPV in esophageal carcinogenesis with careful consideration of study design and laboratory detection method, providing more accurate assessment of the HPV status in esophageal cancer.

• Molecules and Cells
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• 제44권1호
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• pp.26-37
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• 2021

Human papillomaviruses (HPVs) cause cellular hyperproliferation-associated abnormalities including cervical cancer. The HPV genome encodes two major viral oncoproteins, E6 and E7, which recruit various host proteins by direct interaction for proteasomal degradation. Recently, we reported the structure of HPV18 E7 conserved region 3 (CR3) bound to the protein tyrosine phosphatase (PTP) domain of PTPN14, a well-defined tumor suppressor, and found that this intermolecular interaction plays a key role in E7-driven transformation and tumorigenesis. In this study, we carried out a molecular analysis of the interaction between CR3 of HPV18 E7 and the PTP domain of PTPN21, a PTP protein that shares high sequence homology with PTPN14 but is putatively oncogenic rather than tumor-suppressive. Through the combined use of biochemical tools, we verified that HPV18 E7 and PTPN21 form a 2:2 complex, with a dissociation constant of 5 nM and a nearly identical binding manner with the HPV18 E7 and PTPN14 complex. Nevertheless, despite the structural similarities, the biological consequences of the E7 interaction were found to differ between the two PTP proteins. Unlike PTPN14, PTPN21 did not appear to be subjected to proteasomal degradation in HPV18-positive HeLa cervical cancer cells. Moreover, knockdown of PTPN21 led to retardation of the migration/invasion of HeLa cells and HPV18 E7-expressing HaCaT keratinocytes, which reflects its protumor activity. In conclusion, the associations of the viral oncoprotein E7 with PTPN14 and PTPN21 are similar at the molecular level but play different physiological roles.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제40권
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• pp.16.1-16.5
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• 2018

Background: Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder, characterized by multifocal expression, progressive clinical evolution, and a high rate of malignant transformation. Evidence-based information regarding optimal PVL management is lacking, due to the paucity of data. The present report describes a case of PVL associated with HPV-16 infection and epithelial dysplasia treated by diode laser surgery, and the outcome of disease clinical remission over a 2-year follow-up period. Case report: A 61-year-old Caucasian male with oral verrucous hyperkeratosis presented for diagnosis. The lesions were localized on the maxillary gingiva and palatal alveolar ridge. Multiple biopsy specimens have been taken by mapping the keratotic lesion area. Microscopic examination was compatible with a diagnosis of PVL with focal mild dysplasia, localized in the right maxillary gingiva. Polymerase chain reaction (PCR) was done for human papillomavirus (HPV) detection which revealed presence of HPV DNA, and the genotype revealed HPV 16 in the sample. The PVL in the right gingival area was treated on an outpatient basis by excision with a diode laser. This approach resulted in good clinical response and decreased morbidity over a 2-year follow-up period. Conclusions: This case illustrates the benefit of a conservative approach by diode laser treatment than wide surgical excision for management of the PVL lesions associated with mild dysplasia and HPV-16 infection.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7357-7362
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• 2014

Interleukin-6 (IL-6), a central proinflammatory cytokine, maintains immune homeostasis and also plays important roles in cervical cancer. Therefore, we aimed to evaluate any associations of IL-6 gene polymorphisms at positions -174 and -572 with predisposition to cervical cancer in a Chinese population. The present hospital-based case-control study comprised 518 patients with cervical cancer and 518 healthy controls. Polymorphisms of the IL-6 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Patients with cervical cancer had a significantly higher frequency of the IL-6 -174 CC genotype [odds ratio (OR) =1.52, 95% confidence interval (CI) = 1.06-2.19; p=0.02], IL-6 -572 CC genotype (OR =1.91, 95% CI = 1.16-3.13; p=0.01) and IL-6 -174 C allele (OR =1.21, 95% CI = 1.02-1.44; p=0.03) compared to healthy controls. When stratifying by the FIGO stage, patients with III-IV cervical cancer had a significantly higher frequency of IL-6 -174 CC genotype (OR =1.64, 95% CI =1.04-2.61; p=0.04). The CC genotypes of the IL-6 gene polymorphisms at positions -174 and -572 may confer a high risk of cervical cancer. Additional studies with detailed human papillomavirus (HPV) infection data are warranted to validate our findings.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.6127-6130
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• 2013

This study aimed to investigate the association between p53 Arg72Pro polymorphism and the risk of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) by conducting meta-analysis. The PubMed database was searched for relevant studies until May 30, 2013. Relevant studies were selected and data were extracted by two independent authors. Overall, subgroup, and sensitivity analyses were then conducted using the Comprehensive Meta-Analysis v2.2 software. Wild-genotype ArgArg was considered as reference [odds ratio (OR) = 1.00]. Nine studies involving 1071 HNSCC cases were obtained. Meta-analysis results indicated no association between p53 Arg72Pro polymorphism and the risk of HPV-related HNSCC: for Pro/Pro vs. Arg/Arg, OR = 1.17, 95% confidence interval (CI) = 0.70-1.98; for Arg/Pro vs. Arg/Arg, OR = 1.25, 95% CI = 0.97-1.72; and for (Pro/Pro + Arg/Pro) vs. Arg/Arg, OR = 1.28, 95% CI = 0.95-1.70. These meta-analysis results were supported by subgroup and sensitivity analysis results. In conclusions, p53 Arg72Pro polymorphism is a potential marker of HP infection-related HNSCC rather than a susceptibility gene polymorphism.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.57-64
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• 2016

Background: Tobacco smoking is considered a risk factor for cervical cancer development due to the presence of tobacco based carcinogenic metabolites in cervical cells of female smokers. In this study, we investigated the role of the T3801C (MspI) polymorphism of CYP1A1, a gene encoding an enzyme necessary for the initiation of tobacco based carcinogen metabolism, on cervical cancer risk. The T to C substitution may alter CYP1A1 activities, potentially elevating cervical cancer risk. Since results of gene-disease association studies vary according to the study population, the multi-ethnic population of Malaysia provides an excellent representative cohort for identifying and comparing the cervical cancer risk among the 3 major ethnics in Southeast Asia in relation to CYP1A1 MspI polymorphism. Materials and Methods: A total of 195 Thin Prep Pap smear samples from HPV negative and cancer free females were randomly selected as controls while 106 formalin fixed paraffin embedded samples from females with invasive cervical cancer were randomly selected for the cases group. The polymorphisms were identified using restriction fragment length polymorphism (RFLP) PCR. Results: We found no significant associations between CYP1A1 MspI polymorphism and cervical cancer in the general Malaysian female population. However, upon ethnic stratification, the variant C/C genotype was significantly associated with a 4.66-fold increase in cervical cancer risk in Malay females (95% CI= 1.21-17.9; p=0.03). No significant association was observed in the Chinese and Indian females. Additionally, there were no significant associations in the dominant model and allele frequency model analysis in both the general and ethnically stratified female population of Malaysia. Conclusions: Our findings suggest that the C/C genotype of CYP1A1 MspI polymorphism is associated with the development of cervical carcinoma in the Malay females of Malaysia.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3117-3120
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• 2015

Objective: Interferon-${\gamma}$ (IFN-${\gamma}$) and signal transducers and activators of transcription (STATs) each play an important role in carcinogenesis associated with viral infection. Cervical cancer is almost invariably associated with infection by human papillomavirus (HPV), and previous studies suggested that dysregulation of the signal pathway involved in IFN-${\gamma}$ and STATs is associated. Our objective was to evaluate the association of SNPs in STAT2, STAT3, and IFN-${\gamma}$ with cervical cancer susceptibility in Chinese Han women in Hunan province. Materials and Methods: Genomic DNA was extracted from peripheral blood samples of 234 cervical cancer patients and 216 healthy female controls. STAT2 and STAT3 genotyping was performed using polymerase chain reaction-restriction enzyme (PCR-RE) analysis. IFN-${\gamma}$ genotyping was detected by PCR-amplification of specific allele (PASA). Results: For STAT2 rs2066807 polymorphisms, there was no significant difference of genotype distribution (P=0.827) and allele frequencies (P=0.830, OR=1.09, 95% CI: 0.51-2.31) between cases and controls. For STAT3 rs957970 polymorphisms, there was no significant difference of genotype distribution (P=0.455) and allele frequencies (P=0.560, OR=0.92, 95% CI: 0.71-1.20) between cases and controls. For IFN-${\gamma}$ +874A/T polymorphisms, there was no significant difference of genotype distribution (P=0.652) and allele frequencies (P=0.527, OR=1.12, 95% CI: 0.79-1.59) between cases and controls. Conclusion: These results suggest that polymorphisms in STAT2, STAT3 and IFN-${\gamma}$ genes are not likely to be strong predictors of cervical cancer in Han women in southern China.