• International Journal of Oral Biology
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• v.32 no.3
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• pp.93-101
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• 2007

Cell behavior of the transformed cells is known to affect by interaction with extracellular matrix (ECM) proteins and integrin. To investigate the alterations of both integrin expression and cell-matrix interaction during neoplastic conversion of human oral kerationcytes, we studied expression levels of integrin subunits by flow cytometry and cellular responses to the ECM proteins in normal human oral keratinocytes (NHOKs), HPV-immortalized HOK-16B line, and three oral cancer cell lines established from HOK-16B line, CTHOK-16B-BaP, CTHOK-16B-DMBA, and CTHOK-16B-Dexa lines. The expression levels of ${\alpha}\;and\;{\beta}$ integrin subunits were shown decreased tendency in human oral keratinocytes undergoing immortalization and tumorigenic transformation except CTHOK-16B-DMBA line tested. Although ${\alpha}v{\beta}6$ integrin is known to be highly expressed in squamous cell carcinomas, and the altered integrin expression is suspected to be associated with cellular carcinogenesis, ${\alpha}v$ integrin subunit and ${\alpha}v{\beta}6$ integrin did not express in oral cancer cell lines tested. Cell behavior to the ECM proteins in HOK-16B line was generally similar to that of exponentially proliferating NHOKs. The adhesion activity profiles of type I collagen were very similar to that of its laminin counterparts, but fibronectin showed minimal adhesion activity under our conditions compared to the BSA control. The ability of the CTHOK-16B-BaP line to spread upon type I collagen and laminin markedly decreased, but migration was notably increased on type I collagen. In contrast, CTHOK-16B-DMBA and CTHOK-16B-Dexa lines spread less but migrated more upon type I collagen than immortalized HOK-16B line. These data indicate that downregulation of integrin subunits causes the changes of cellular responses to the ECM proteins during neoplastic conversion of human oral keratinocytes, and that cellular responses to the ECM proteins in oral cancer cell lines established by exposing different carcinogens are variable according to chemical carcinogens treatment.

• Biomedical Science Letters
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• v.21 no.2
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• pp.69-76
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• 2015

Cervical cancer is the third most common cancer in women worldwide and there is a significant association between human papillomavirus (HPV) infection and cervical cancer. Certain HPV groups, labeled high-risk (HR) HPV groups, are strongly associated with malignancies of the human cervix. HPV prevalence and genotype distribution were analyzed using the REBA $HPV-ID^{(R)}$ (YD Diagnostics, Yongin, Korea) assay based on the reverse blot hybridization assay (REBA) with a total of 324 liquid-based cytology samples from women in Western Shandong Province, East China and results were compared with cytological diagnosis. Most of the HPV genotypes that were detected in high-grade cervical lesions were HR-HPV genotypes such as HPV 16, 18, 33, 53, and 58. The prevalence of these HR-HPV genotypes increased in high-grade cervical lesions. However, from low- to high-grade cervical lesions, the ability to detect LR-HPV genotypes decreased. Additionally, in general, the single HPV genotype infection rate increases in proportion to the severity of the lesion. The study findings suggest that a currently available preventive vaccine against HPV 16 and 18 may have limited effectiveness for prevention of all HPV infection in this province. Finally, based on these findings, these data could guide national or regional vaccination programs in the Western Shandong Province of East China to substantially reduce the burden of cervical lesions.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3961-3968
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• 2015

Background: Variants of human papillomavirus (HPV) show more oncogenicity than do prototypes. The HPV16 Asian variant (HPV16As) plays a major role in cervical cancer of Asian populations. Some amino acid changes in the E6 protein of HPV16 variants affect E6 functions such as p53 interaction and host immune surveillance. This study aimed to investigate activities of HPV16As E6 protein on modulation of expression of miRNA-21 as well as interferon regulatory factors (IRFs) 1, 3, 7 and c-fos. Materials and Methods: Vectors expressing E6 protein of HPV16As (E6D25E) or HPV16 prototype (E6Pro) were constructed and transfected into C33A cells. HCK1T cells expressing E6D25E or E6Pro were established by transducing retrovirus-containing E6D25E or 16E6Pro. The E6AP-binding activity of E6 and proliferation of the transfected C33A cells were determined. MiR-21 and mRNA of interesting genes were detected in the transfected C33A cells and/or the HCK1T cells, with or without treatment by culture medium from HeLa cells (HeLa-CM). Results: E6D25E showed binding activity with E6AP similar to that of E6Pro. Interestingly, E6D25E showed a higher activity of miR-21 induction than did E6Pro in C33A cells expressing E6 protein. This result was similar to the HCK1T cells expressing E6 protein, with HeLa-CM treatment. The miR-21 up-regulation significantly corresponded to its target expression. Different levels of expression of IRFs were also observed in the HCK1T cells expressing E6 protein. Interestingly, when treated with HeLa-CM, IRFs 1, 3 and 7 as well as c-fos were significantly suppressed in the HCK1T cells expressing E6D25E, whereas those in the HCK1T cells expressing E6Pro were induced. A similar situation was seen for IFN-${\alpha}$ and IFN-${\beta}$. Conclusions: E6D25E of the HPV16As variant differed from the E6 prototype in its activities on epigenetic modulation and immune surveillance and this might be a key factor for the important role of this variant in cervical cancer progression.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6961-6964
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• 2013

Human papillomavirus (HPV) is a major cause of cervical cancer. More than 100 HPV genotypes have been identified; however the distribution varies geographically and according to ethnicity. The purpose of this study was to investigate the prevalence and distribution of HPV subtypes among Northeast Thai women. Subjects included 198 cases of SCCA and 198 age-matched, healthy controls. HPV-DNA was amplified by PCR using the consensus primers GP5+/6+ system followed by reverse line blot hybridization genotyping. The prevalence of high-risk HPV infection was 21 (10.1%) and 152 (76.8%) in the controls and in the cases, respectively. High-risk HPV significantly increased the risk for cervical cancer with an OR of 42.4 (95%CI: 22.4-81.4, p<0.001) and an adjusted OR of 40.7-fold (95%CI: 21.5-76.8, p <0.001). HPV-16 was the most prevalent HPV type in the SCCA (56.2%) followed by HPV-58 (17.8%) and HPV-18 (13.6%); whereas HPV-58 (46.4%) was a prominent genotype in the controls followed by HPV-16 (39.3%) and unidentified HPV types (25.0%). These findings indicate that HPV infection remains a critical risk factor for SCCA; particularly, HPV-16, HPV-58 and HPV-18. In order to eradicate cervical cancer, sustained health education, promoted use of prophylactics and a HPV-58 vaccine should be introduced in this region.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5861-5865
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• 2013

We investigated the distribution of HPV genotypes in Uyghur women in Xinjiang region of China, and behavioral factors which could predispose them to HPV infection. In this cross-sectional study, women aged 15-59 years were recruited by cluster sampling method in Yutian region in 2009. Liquid-based cytology samples were analyzed centrally for HPV genotype with a linear array detector. Univariate and multivariate logistic regression analyses were performed to identify behavioral risk factors for HPV infection. A total of 883 Uyghur women were recruited successfully. The prevalence of high-risk HPV and low-risk HPV were 7.25% and 1.58%, respectively; the most common HPVs were HPV16, 51, 31, 39 and 58. We found that age of first sexual intercourse was a strong predictor for HPV infection (odds ratio of 4.01 for ${\leq}15$ years versus ${\geq}25$). Having sexual partners ${\geq}3$ was the second predictor (OR 3.69, 95% CI 2.24-7.16). Cleaning the vagina after sex showed an increased risk of HPV infection (OR 2.72; 95% CI 1.98-5.13); Using the condom showed protective factors for HPV infection (OR 0.36; 95%CI0.12-0.53). HPV16, 51, 31, 39 and 58 were the priority types; the age of first sexual intercourse was identified as a major risk factor for HPV infection. Other notable risks were number of sexual partners and cleaning the vagina after sex. Changing these behavioral risk factors could help to reduce the occurrence of cervical cancer in this population.

• Journal of Microbiology and Biotechnology
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• v.31 no.4
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• pp.610-620
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• 2021

There has been increasing interest in the head and neck squamous cell carcinoma (HNSCC) that is caused by high-risk human papillomavirus (HR-HPV) and has posed a significant challenge to Otolaryngologists. A rapid, sensitive, and reliable method is required for the detection of HR-HPV in clinical specimens to prevent and treat HPV-induced diseases. In this study, a multiple cross-linking spiral amplification (MCLSA) assay was developed for the visual detection of HPV-16. In the MCLSA assay, samples were incubated under optimized conditions at 62℃ for 45 min, and after mixing with the SYBR Green I (SGI) dye, the positive amplicons showed bright green fluorescence while the negative amplicons exhibited no obvious change. The specificity test revealed that the developed MCLSA technique had high specificity and could effectively distinguish all five HPV-16 strains from other pathogenic microorganisms. In terms of analytical sensitivity, the limit of detection (LoD) of MCLSA assay was approximately 5.4 × 101 copies/tube, which was 10-fold more sensitive than loop-mediated isothermal amplification (LAMP) and RT-PCR. The detection results of laryngeal cancer specimens collected from 46 patients with suspected HPV infection in the Liaoning region demonstrated that the positive detection rates of MCLSA and hybridized capture 2 kit were 32.61% (15/46). The true positive rate of the MCLSA assay was higher than that of RT-PCR (100% vs. 93.33%) and LAMP (100% vs. 86.67%). Therefore, the MCLSA assay developed in the present study could be a potentially useful tool for the point-of-care (PoC) diagnosis of HR-HPV, especially in resource-limited countries.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6769-6772
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• 2015

Background: High risk human papillomaviruses (HPVs) are the leading cause of cervical cancer (CC) and Pap smear screening has not been successful in preventing CC in Tunisia. HPV vaccination that targets HPV16 and 18 offers a new efficient prevention tool. Identification of HPV types in CC is thus essential to determine the impact of HPV vaccine implementation. The aim of this study is to provide specific data from Tunisia. Materials and Methods: A total of 89 histological confirmed paraffin embedded samples isolated from patients with CC diagnosed between 2001 and 2011 were collected from five medical centres from Northern and Southern Tunisia. HPV DNA was detected using a nested PCR (MY09/MY11-GP5+/GP6+) and genotyping was assessed using a reverse blot line hybridisation assay that enables the detection of 32 HPV types. Results: HPV DNA was detected in all samples. Twelve high risk types were detected; HPV16 and/or 18 were predominant, accounting together for 92.1% of all the CC cases (HPV16: 83.1%). Single infections accounted for 48.8% of the cases and were mostly linked to HPV 16 (32.6%) and less frequently to HPV 18 (2.4%). The other high risk HPV single infections were linked to HPV 35 (4.6%), 45 (4.6%), 58 (2.3%) and 59 (2.3%). Multiple infections with mixing of 2 to 4 genotypes predominately featrued HPV16 and/or 18 with HPV 35 and 45 (96.6 %) and less frequently with HPV 59, 40, 66, 73 and 58. There was no statistically significant variation in the relative distribution of HPV types with age. Conclusions: These results strongly indicate that prophylactic HPV vaccines can have a major impact in preventing CC in Tunisia.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6193-6200
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• 2015

Head and neck cancer, including oral cancer, is the sixth most common cancer in humans worldwide. More than 90% of oral cancers are of squamous cell carcinoma type. Recent studies have shown a strong relationship between human papillomavirus (HPV) infection and head and neck cancer, especially oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). Moreover, the incidence of HPV-related OSCC appears to be on the rise while HPV-unrelated OSCC tends to have stabilized in the past decades. p16, a tumor suppressor gene, normally functions as a regulator of the cell cycle. Upon infection with high-risk types of HPV (HR-HPV), particularly types 16, 18, 31, 33, 34, 35, 39, 51, 52, 56, 58, 59, 66, 68, and 70, the expression of p16 is aberrantly overexpressed. Therefore, the expression of p16 is widely used as a surrogate marker for HPV infection in head and neck cancer.

• Imaging Science in Dentistry
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• v.46 no.4
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• pp.285-290
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• 2016

In this report, we describe the incidental finding of an oropharyngeal mass in a patient who presented with a chief complaint of temporomandibular pain. The patient was initially evaluated by an otorhinolaryngologist for complaints of headaches, earache, and sinus congestion. Due to worsening headaches and trismus, he was further referred for the management of temporomandibular disorder. The clinical evaluation was uneventful except for limited mouth opening (trismus). An advanced radiological evaluation using magnetic resonance imaging revealed a mass in the nasopharyngeal/oropharyngeal region. The mass occupied the masticatory space and extended superioinferiorly from the skull base to the mandible. A diagnostic biopsy of the lesion revealed a long­standing human papilloma virus (HPV­16)­positive squamous cell carcinoma of the oropharynx. This case illustrates the need for the timely radiological evaluation of seemingly innocuous orofacial pain.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2667-2672
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• 2016

Background: Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV). Cancer of the cervix is the third or even the second most common cancer in women worldwide, more than 85% of the cases occurring in developing countries, such as China and India, including the Republic of Kazakhstan. The purpose was to determine the HPV type distribution to evaluate efficacy of vaccination and adjust cancer prevention strategy in Western Kazakhstan in the future. Materials and Methods: A retrospective analysis was conducted of data obtained from PCR laboratories in 4 regional centers for the time period covering 12 months, 2013-2014, using AmpliSens$^{(R)}$ Real-Time PCR kits for HPV testing of 12 genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59). Results: A total of 1,661 persons were HPV tested within 2013-14, but a proprotion examined for 16 and 18 genotypes only (563) was not been included for statistic analysis of distribution and ratio of the most common genotypes. Males accounted for only a small number (N=90 in total). Conclusions: Total number of the HPV-positive appeared to be 26.0%, or 286 of N=1098. Types distribution was as follows: type 16 (10.7%), 39 (5.83%), 51 (5.27%), 31 (4.85%), 56 (4.58%), 18 (3.61%), 59 (2.64%), 58 (2.22%), 35 (1.94%), 33 (1.25%). Overall the HPV infection was highest in 16-29 years old (62.4%) and decreased with age. Total prevalence of the HR-HPVs amongst male population was 21.4% with top five types 16, 18, 39, 51, 31. Trends forcorrelations between Aktau site and type 33 (Cramer's V 0.2029), between Caucasian ethnicity and type 33 (Cramer's V .1716), and between European ethnicities in Uralsk and type 45 (Cramer's V .1752) were found. Of N 563 tested separately for 16 or 18 types, 13.6% were positive. As a whole, the distribution of 16/18 types had a ratio of 3.53:1. Given the vaccine-targeted type 16 is widely spread amongst this regional population, HPV immunization program of adolescent girls 10-13 years should be implemented appropriately.