• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.785-790
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• 2013

Background: Persistent infection of one or more of about 15 high-risk human papillomaviruses (HR-HPVs), most commonly HPV types 16/18, has a significant role in cervical cancer initiation and progression. There are limited data available from north-east India about HPV prevalence though this region has high incidence rates of cervical cancer. The aim of this study was to investigate the HPV genotypes prevalent in cervical cancer patients of north-east India. Materials and Methods: We analyzed 107 cervical cancer patient samples. Nested multiplex PCR assays were employed for detection of 13 high risk and 5 low risk HPV types. Results: HPV was confirmed in 105 samples. The presence of 6 'carcinogenic' HPV types, HPV-16 (88%), -18 (15%), -31(4%),-45 (3%), -59 (4%), -58(1%), and one non carcinogenic, HPV-6/11 (6%), was recorded. Among various demographic and clinical factors only tumour stage showed a statistically significant association with HPV type infection (P=0.019). Conclusions: We suggest that the most prevalent genotype is HPV-16 followed by HPV-18 in cervical carcinoma patients of the north-eastern region of India. Advanced tumour stage may be associated with increased possibility of harbouring multiple HPV genotypes.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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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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• v.17 no.8
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• pp.4149-4154
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• 2016

Background: Cervical carcinoma is one of the main causes of mortality in women worldwide as well as in India. It occurs as a result of various molecular events that develop from the combined influences of an individual's genetic predisposition and external agents such as smoking and menstrual hygiene, for example. However, infection with human papillomavirus (HPV) is the established major risk factor. The aim of the current study was to investigate p16 CpG island methylation and establish any correlation with mRNA expression in north Indian population. Materials and Methods: We analyzed 196 woman volunteer out of which 98 were cases and 98 healthy controls. For the analysis of methylation pattern, DNA extracted from blood samples was modified with a bisulfate kit and used as template for methylation specific PCR (MSP). Quantitative real-time PCR (QRT-PCR) was performed to check mRNA expression. Results: Correlation between methylation status of p16 gene and poor menstrual hygiene was significant (p=0.006), high parity cases showed methylation of p16 gene (p=0.031) with increased risk up to 1.86 times for cervical cancer and smoking was a strong risk factor associated with cervical cancer. We analyzed methylation pattern and found 60.3% methylation in cases with low mRNA expression level (0.014) as compare to controls (1.24). It was also observed that promoter methylation of p16 gene was significantly greater in FIGO stage III. Conclusions: We conclude that p16 methylation plays an important role in cervical cancer in the north Indian population and its methylation decreases mRNA expression. It can be used as an important and consistent blood biomarker in cervical cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3843-3847
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• 2015

Background: Cervical cancer is the second most common cause of cancer related death of women. Persistent HPV infection, especially with high-risk types such as HPV16 and HPV18, has been identified to be the primary cause of cervical cancer. E6 and E7 are the major oncoproteins of high-risk HPVs, which are expressed exclusively in HPV infected tissues, and thereby represent ideal therapeutic targets for immunotherapy of cervical cancer. Materials and Methods: In this work, we used recombinant adenovirus expressing coden-optimized HPV16 E6 and E7 fusion protein (Ad-ofE6E7) to prime dendritic cells (DC-ofE6E7), to investigate the ability of primed DC vaccine in eliciting antitumor immunity in vitro and vivo. Results: Our results indicated that DC-ofE6E7 vaccine co-culturing with splenocytes could strongly induce a tumor-specific cytotoxic T lymphocyte (CTL) response and kill the TC-1 cells effectively in vitro. Moreover, DC-ofE6E7 vaccine induced protective immunity against the challenge of TC-1 cancer cells in vivo. Conclusions: The results suggested that the HPV16 ofE6E7 primed DC vaccine has potential application for cervical cancer immunotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4135-4141
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• 2014

Background: Human papillomaviruses (HPV) may play an important role as one of the possible etiologies of oral squamous cell carcinoma (OSCC). The present study aimed to investigate the association between HPV and OSCC in young Japanese patients by examining the presence of HPV DNA and surrogate markers in OSCC tissues. Materials and Methods: Forty young patients with OSCC whose surgical specimens were available were analyzed and compared with 40 patients randomly recruited from a pool of patients aged >40 years. HPV DNA was detected using the polymerase chain reaction-based AMPLICOR$^{(R)}$ HPV test, and surrogate markers of HPV infection were analyzed using immunohistochemical techniques to detect $p16^{INK4a}$ and p53. Results: Only two (5%) young patients and one (2.5%) older patient were positive for HPV DNA. $p16^{INK4a}$ overexpression was identified in six (15%) young patients. p53 staining levels were not high in tissues of most young patients (27 patients, 67.5%). HPV DNA status did not significantly correlate with $p16^{INK4a}$ expression levels. Profiles of increased levels of $p16^{INK4a}$ expression with diminished levels of p53 staining were not associated with the presence of HPV DNA. The combined p53 with $p16^{INK4a}$ profiles were significantly correlated with alcohol consumption in younger patients (p=0.006). Conclusions: Results of the present study indicate that HPV is less likely to cause OSCC in young Japanese patients, and the $p16^{INK4a}$ expression level is not an appropriate surrogate marker for HPV infection in OSCC.

• Korean Journal of Food Science and Technology
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• v.32 no.6
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• pp.1389-1395
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• 2000

Cervical cancer has been one of the leading causes of female death from cancer worldwide with about 500,000 deaths per year. A strong association between certain human papillomaviruses (HPV types 16 and 18) and cervical cancer has been well known. An extract of natural products, Rhus, has been used to investigate whether this agent has the ability of inhibiting the oncogenes E6 and E7 of HPV type 16. This Rhus inhibited the proliferation of human cervical cancer cell lines (C-33A, SiHa, Caski) and HaCaT keratinocytes in a dose response manner. In vitro binding assay and ELISA showed that Rhus inhibited the in vitro binding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53. In addition, Rhus inhibited the in vitro binding of E7 and Rb which essential tumor suppressor for the control of cell cycle. The level of mRNA for E6 was also decreased by Rhus while that of E7 mRNA was not changed. Our data suggested that Rhus inhibited the oncogenecity of E6 and E7 of HPV 16 type, thus can be used as a putative anti-HPV agent for the treatment of cervical carcinomas by HPV.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.4
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• pp.259-266
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• 2015

Cervical cancer is the third most common cancer among women worldwide. Cervical cancer is significantly associated with human papillomavirus (HPV) infection. The prevalence of HPV infection is influenced by geography, immune status, sexual history and genetic factors. For example, geographically, HPV prevalence varies from 1.5% to 39%. However, little is known about the relationship between HPV prevalence and age. An analysis of HPV prevalence by age will help determine when high-risk groups are exposed to HPV. Such an analysis could also demonstrate a correlation between specific HPV genotypes and age. In addition, the analysis might clarify the optimum age for using vaccines. In this study, HPV prevalence and genotype distribution among Korean and Chinese women are analyzed by age. The REBA HPV-ID$^{(R)}$ assay (YD diagnostics, Yong-in, Republic of Korea) was used for detecting HPV genotypes in uterine cervical liquid-based cytology samples from 533 women from Korea and 324 from East China (Western Shandong province. Women with severe dysplasia such as SCC (Squamous cell carcinoma) and HSIL (High-grade squamous intraepithelial lesion) groups were primarily in their 40s and 50s, whereas women with mild and moderate dysplasia (ASCUS and LSIL groups) were primarily in their 30s and 40s. Women with HPV genotype 16 and 18 infections were primarily in their 40s. The results suggest that HPV infection is associated with certain age groups in the Korean population.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3837-3841
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• 2013

Objectives: To analyse HPV integration prevalence and genotype distributions in cervical intraepithelial neoplasia (CIN) in east part of China, furthermore to assess preferential sites for common HPV integrations and provide baseline information for cervical abnormality screening and prevention. Methods: Integration of HPV in 113 paraffin-embedded cervical intraepithelial neoplasia samples was assessed using Gencap technology in Key Laboratory of Biotechnologies in BGI-Shenzhen. Results: 64 samples were HPV-integrated and as the cervical lesions increased, the integration rate became higher significantly (P=0.002). Fifteen different HPV genotypes were detected, 14 high-risk (16, 18, 31, 33, 51, 52, 56, 58, 66, 68) and 1 low-risk (11). The most common genotypes were HPV-16, 58, 33, 52, 66, and 56. Thirteen patients had co-integration involving mainly HPV-16 and 58. The frequency of HPV gene disruption was higher in L1 and E1 genes than in other regions of the viral genomes. Conclusion: Some 56.6% of CIN lesions in Qingdao had HPV integrations, and 67.2% of HPV-integrated patients were HPV-16 and 58, more prone to be integrated in younger patients below 45 years old. There exist preferential sites for HPV-16 and HPV-58 integration, and they are more likely to be disrupted in the L1 and E1 loci.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5525-5529
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• 2015

Background: Currently it is believed that human papillomaviruses (HPV) are associated with the development of some oral/oropharyngeal cancers. It has been suggested that these viruses influence carcinogenesis in both smokers and non-smokers. Data on the prevalence of HPV in healthy adults are thus needed to estimate the risk of oral/oropharyngeal cancer. The aim of this study was to assess the prevalence of oral HPV in healthy female adults in Indonesia and Thailand. Materials and Methods: Healthy female students from the Faculties of Dentistry of Universitas Indonesia and Chiang Mai University were asked to participate in this pilot study. DNA was extracted from saliva specimens and screened for HPV16 and HPV18 using PCR. Results: The age, marital status and sexual experience of the subjects between the two countries were not significantly different. Eight (4%) and 4 (2%) samples were positive for HPV16 and HPV18, respectively. Fisher's Exact test found a significant difference between HPV16 positivity in subjects who were married and had sexual intercourse but not for HPV18. Conclusions: This study successfully detected presence of HPV16 and HPV18 DNA in a number of saliva samples from female dental school students. Marital status, experience of sexual intercourse and safe sexual practice are related to the possibility of finding HPV DNA finding in saliva. Dentists, physicians and other health care professionals may gain significant value from the findings of this study, which provide an understanding of the nature of HPV infection and its risk to patient health and disease.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5861-5865
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• 2014

High risk forms of the human papilloma virus (HPV) are generally accepted as necessary causative agents for cervical cancer. Recently, a possible relation between HPV and oral squamous cell carcinoma (OSCC) has also been noticed. The present study was conducted to investigate the prevalence of HPV infection in OSCCs in Wuhan city. DNA samples were collected from fresh tissues in 200 patients with OSCC and 68 normal controls. The polymerase chain reaction and direct sequencing were used to identify the HPV types in the samples. The prevalence of HPV of all types in the OSCC group was higher than in the control group (55/200 vs 2/68, OR=11.5, 95% CI=2.6-50.2). HPV16 and HPV18 were the main types detected, with HPV6 was the only low-risk type identified. High-risk HPV types HPV16 and HPV18 are prevalent in OSCC patients and may participate in the development of OSCC with traditional risk factors, tobacco and alcohol, possibly exerting synergistic effects. The results of multinomial logistic regression showed that those who smoked, consumed alcohol and with HPV infection have the highest risk of developing oral cancer (OR=13.3, 95% CI=3.1-56.8). Adjusted for age, smoking and alcohol use, HPV infection was independently associated with oral squamous cell carcinoma.