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Objective: Human papillomavirus (HPV) vaccination was introduced in Japan in April 2013, as a national immunization program for girls aged 12–16 years, after an initial introduction in 2010 as a public-aid program for girls aged 13–16 years. The Yuri-Honjo district had the highest vaccine coverage among women aged 17–51 years in 2017, due to the original public-aid program. The aim of this study was to evaluate the differences in the vaccine types of HPV16/18 infections between 2008–2012 (pre-vaccine era) and 2013–2017 (vaccine era).Materials and Methods: We evaluated whether HPV vaccination was associated with a decrease in the prevalence of HPV16/18 and high-risk HPV and the incidence of HPV-associated cervical lesions. A total of 1,342 women aged 18–49 years, covering both the pre-vaccine and vaccine eras, who visited Yuri Kumiai General Hospital and underwent HPV genotype tests from June 2008 to December 2017 were compared.Results: Among women aged 18–24 years with higher vaccine coverage (68.2%), the prevalence of HPV16/18 and high-risk HPV decreased from 36.7% and 69.4%, respectively, in the pre-vaccine era to 5.8% and 50.0%, respectively, in the vaccine era (p=0.00013 and p=0.047, respectively). Among those with cervical intraepithelial neoplasia grade 2− and grade 2+, HPV16/18 prevalence decreased from 30.0% to 2.7% (p=0.0018) and from 81.8% to 36.4% (p=0.030), respectively. In this age group, the rate of HPV16/18 positivity decreased significantly. Among age groups with lower vaccine coverage, HPV prevalence did not significantly differ between the two eras.Conclusion: The prevalence of HPV16/18 and high-risk HPV significantly decreased in women aged 18–24 years, most of whom were vaccinated. HPV vaccination effectively reduced the prevalence of HPV16/18 infections in the Yuri-Honjo district.
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Abstract This study aimed to explore: 1) DNA methylation in the promoter regions of Wilms tumor gene 1 (WT1), NK6 transcription factor related locus 1 gene (NKX6-1) and Deleted in bladder cancer 1 (DBC1) gene in cervical cancer tissues of Uygur women in Xinjiang, and 2) the correlation of gene methylation with the infection of HPV16/18 viruses. We detected HPV16/18 infection in 43 normal cervical tissues, 30 cervical intraepithelial neoplasia lesions (CIN) and 48 cervical cancer tissues with polymerase chain reaction (PCR) method. Methylation in the promoter regions of the WT1, NKX6-1 and DBC1 genes in the above-mentioned tissues was measured by methylation-specific PCR (MSP) and cloning sequencing. The expression level of these three genes was measured by real-time PCR (qPCR) in 10 methylation-positive cervical cancer tissues and 10 methylation-negative normal cervical tissues. We found that the infection of HPV16 in normal cervical tissues, CIN and cervical cancer tissues was 14.0, 36.7 and 66.7%, respectively. The infection of HPV18 was 0, 6.7 and 10.4%, respectively. The methylation rates of WT1, NKX6-1 and DBC1 genes were 7.0, 11.6 and 23.3% in normal cervical tissues, 36.7, 46.7 and 30.0% in CIN tissues, and 89.6, 77.1 and 85.4% in cervical cancer tissues. Furthermore, WT1, NKX6-1 and DBC1 genes were hypermethylated in the high-grade squamous intraepithelial lesion (CIN2, CIN3) and in the cervical cancer tissues with infection of HPV16/18 (both P< 0.05). The expression of WT1, NKX6-1 and DBC1 was significantly lower in the methylation-positive cervical cancer tissues than in methylation-negative normal cervical tissues. Our findings indicated that methylation in the promoter regions of WT1, NKX6-1 and DBC1 is correlated with cervical cancer tumorigenesis in Uygur women. The infection of HPV16/18 might be correlated with methylation in these genes. Gene inactivation caused by methylation might be related to the incidence and development of cervical cancer.
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Objective: To investigate the clinical significance and predictive value of human papillomavirus (HPV) 16/18 E6 protein in the different cervical intraepithelial neoplasia. Methods: The expression of HPV16/18 E6 in 10 normal cervical tissues, 33 cervical intraepithelial neoplasia I (CIN I ), 31 CIN II-III, 30 cervical cancers was detected by immunohistochemistry, explored the expression difference and the relationship with the clinicopathological characteristics of cervical cancer and the prognosis of different CIN. Results: The positive expression rates of HPV16/18 E6 in normal cervical tissues, CIN I, CIN II-III and cervical cancer group were up-regulated (χ2=19.82, P=0.000). HPV16/18 E6 increased positive expression rates in the low grade and the big size tumors of cervical cancer tissues were detected (P=0.033, P=0.011). There were positive correlations between the overexpression and the pathological grade, tumor size, poor prognosis of cervical cancers respectively (r=0.456, P=0.011; r=0.578, P=0.000; r=0.645, P=0.000). The sensitivity, specificity, and diagnostic accuracy rates of HPV16/18 E6 positive expression to the progression of CIN I, CIN II-III and cervical cancer were respectively 100.00%, 62.50%, 43.75%; 96.77%, 91.30%, 92.86%; 96.97%, 83.87%, 66.67%. Conclusion: HPV16/18 E6 overexpression plays an important role in the generation, development and the poor prognosis of cervical cancer. HPV16/18 E6 has a good predictive value for the prognosis and hierarchical management of cervical diseases.
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Objective·To investigate the clinical significance and predictive value of human papillomavirus (HPV) 16/18 E6 protein in the different cervical intraepithelial neoplasia. Methods·The expression of HPV16/18 E6 in 10 normal cervical tissues, 33 cervical intraepithelial neoplasiaⅠ (CINⅠ ), 31 CINⅡ- Ⅲ, 30 cervical cancers was detected by immunohistochemistry, explored the expression difference and the relationship with the clinicopathological characteristics of cervical cancer and the prognosis of different CIN. Results·The positive expression rates of HPV16/18 E6 in normal cervical tissues, CINⅠ , CINⅡ - Ⅲ and cervical cancer group were up-regulated (χ2=19.82, P=0.000). HPV16/18 E6 increased positive expression rates in the low grade and the big size tumors of cervical cancer tissues were detected (P=0.033, P=0.011). There were positive correlations between the overexpression and the pathological grade, tumor size, poor prognosis of cervical cancers respectively (r=0.456, P=0.011; r=0.578, P=0.000; r=0.645, P=0.000).The sensitivity,specificity,and diagnostic accuracy rates of HPV16/18 E6 positive expression to the progression of CINⅠ,CINⅡ-Ⅲand cervical cancer were respectively 100.00%, 62.50%, 43.75%; 96.77%, 91.30%, 92.86%; 96.97%, 83.87%, 66.67%. Conclusion·HPV16/18 E6 overexpression plays an important role in the generation, development and the poor prognosis of cervical cancer. HPV16/18 E6 has a good predictive value for the prognosis and hierarchical management of cervical diseases.
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Background and purpose:In recent years, epigenetics research has become a new direction of cancer research. A large number of results have shown that the abnormal changes of epigenetic modifications have close connection with cancer. Genome-wide epigenetic modifications have become new markers for cancer. This study aimed to investigate the methylation of the promoter ofDBC1 gene in cervical cancer tissues of Uyghur women in Xinjiang, to explore the correlation between the gene methylation and the infection of HPV, and to evaluate whether it can be used as a tool with high sensitivity and specificity for cervical cancer screening.Methods:This study detected the infection of HPV16, 18 in 43 normal cervical tissues, 35 cervical intraepithelial neoplasia tissues and 54 cervical cancer tissues using the polymerase chain reaction (PCR) method. The methylation of the promoter ofDBC1 gene in above-mentioned tissues was detected by the methylation-specific PCR method. The expression ofDBC1 at mRNA level was measured by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) in 10 methylation-negative normal cervical tissues and 10 methylation-positive cervical cancer tissues.Results:In normal cervical tissues, CIN tissues and cervical cancer tissues, the infection ratios of HPV16 were 18.6%, 34.3% and 68.5%, respectively; the infection ratios of HPV18 were 2.3%, 8.6% and 16.7%, respectively; and the methylation ratios ofDBC1 gene were 23.3%, 40.0%, 87.0%, respectively. In 79 high-grade squamous intraepithelial lesions (CINⅡ and Ⅲ) and cervical cancer tissues, 50 of 79 were infected with HPV16/18, while 29 of 79 were negative. The methylation ratio ofDBC1 gene was 88.0% in HPV16/18 infection positive group while the methylation ratio was 55.2% in negative group (P<0.05). The expression ofDBC1 gene at mRNA level in 10 methy- lation-positive cervical cancer tissues was significantly lower than that in the 10 methylation-negative normal cervical tissues (P<0.05).Conclusion:The methylation ofDBC1 gene may become a molecular marker to detect cervical cancer of Uyghur women in Xinjiang.DBC1 gene methylation combined with HPV16/18 infection test can be used to aid diagnosis of cervical cancer.
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OBJECTIVE: To validate the efficacy of Seeplex HPV4A ACE for the detection of high-risk (HR) human papillomavirus (HPV) and HPV 16 and/or HPV 18 genotypes as compared to the PCR method and the Cervista HPV assays in cervical swab samples. METHODS: Besides liquid-based cytology, additional 97 cervical swab samples were collected for HPV genotyping by HPV4A ACE, Cervista HPV assays, and PCR method. To check the statistical differences, we also conducted the paired proportion test, Cohen's kappa statistic, and a receiver operating characteristic curve. RESULTS: Seeplex HPV4A ACE and the Cervista HPV HR showed substantial agreement with PCR for detection of HR HPVs (88.3%, kappa=0.767 and 81.7%, kappa=0.636, respectively). Seeplex HPV4A ACE also showed substantial agreement with the Cervista HPV 16/18 test (89.5%, kappa=0.628). Additionally, the sensitivity and specificity of Seeplex HPV4A ACE and Cervista HPV HR were 91.4% vs. 84.5% and 73.4%, vs. 72.7%, respectively, when those higher than low-grade squamous intraepithelial lesions were regarded as abnormalities. HPV genotyping for HPV 16/18 detected cervical intraepithelial neoplasias (CINs) better than HR HPV tests (66.7% vs. 24.6% by HPV4A ACE, 52.6% vs. 25.9% by Cervista HPV assays in CIN II or more, relatively). CONCLUSION: Seeplex HPV4A ACE is an effective method as the PCR and the Cervista HPV assays for the detection of HR HPVs and for genotyping of HPV 16 and 18.
Subject(s)
Humans , Uterine Cervical Dysplasia , Chimera , Genotype , Human papillomavirus 16 , Human papillomavirus 18 , Polymerase Chain Reaction , ROC Curve , Sensitivity and SpecificityABSTRACT
The human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine has been demonstrated to be highly efficacious and immunogenic with a favorable safety profile. This study assessed the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Korean girls aged 10-14 yr. This multi-center, observer-blind trial randomly assigned 321 healthy girls to receive three doses (0, 1, 6-month schedule) of HPV-16/18 AS04-adjuvanted vaccine or hepatitis A vaccine. Immunogenicity against vaccine antigens was assessed one month post-Dose 3. Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded. In the according-to-protocol analysis, all initially seronegative subjects vaccinated with the HPV-16/18 AS04-adjuvanted vaccine had seroconverted at Month 7, with a peak geometric mean titer (GMT) that was 600-fold higher than the natural infection titer of 29.8 EU/mL for HPV-16 and a peak GMT that was 400-fold higher than the natural infection titer of 22.6 EU/mL for HPV-18. The vaccine was well tolerated with no increase in reactogenicity with subsequent doses and no reports of vaccine-related SAEs. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine is shown to be highly immunogenic and generally well-tolerated in Korean girls aged 10-14 yr.
Subject(s)
Adolescent , Child , Female , Humans , Adjuvants, Immunologic/administration & dosage , Aluminum Hydroxide/administration & dosage , Antibodies, Viral/analysis , Hepatitis A/immunology , Hepatitis A Vaccines/administration & dosage , Lipid A/administration & dosage , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines/administration & dosage , Republic of Korea , Seroepidemiologic Studies , Uterine Cervical Neoplasms/prevention & controlABSTRACT
Objective:To investigate the expression and significance ofp16INK4a and HPV16/18 in atypical squamous cells of undetermined significance(ASC-US),atypical squamous cells,cannot exclude high-grade squamous intraepithelial lesion(ASC-H),low-grade squamous intraepithelial lesion(LSIL),high-grade squamous intraepithelial lesion(HSIL).Methods:p16INK4a and HPV16/18 DNA in thin-layer slides from 89 specimens were detected by immunohistochemistry and the insitu hybridization.Results:A positive correlation was found between the positive rate of p16INK4a and cervical disease progression,the positive rate of p16INK4a in LSIL,HSIL,ASC-H were higher than ASC-US(P
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BACKGROUND AND OBJECTIVES: Mounting evidence suggests that human papillomavirus (HPV) might play an etiologic role in head and neck cancers. Both epidemiologic and molecular data support that certain types of HPV, such as HPV-16,-18 are associated with specific clinical and pathological characteristics and these are classified into high risk group. The aims of this study were to analyze the relationship between the presence of HPV in tissues from patients with laryngeal cancer and clinicopathologic characteristics. MATERIALS AND METHODS: HPV was detected in 39 laryngeal cancer specimens and 12 cervical lymph node tissue by polymerase chain reaction (PCR). To identify the types of HPV, positive results specimens were examined by PCR with HPV-16,-18 E6 type specific primer. RESULTS: HPV was detected in 9 cases (23.1%) among the 39 laryngeal cancers. Detection rate was higher in the tumors that infiltrate less than 1cm to the parenchyme (p=0.032). HPV-16 was detected in 5 cases (12.8%), HPV-18 in 1 case (2.6%). In cervical lymph node, HPV was found not only in histologically positive nodes (22.2%), but also in histologically negative nodes (33.3%). CONCLUSION: The results of this study suggest that types of HPV have no relationship with clinicopathologic parameters and that HPV play a role not only in the early stage tumorigenesis but also in the cervical lymph node metastasis.
Subject(s)
Humans , Carcinogenesis , Head , Human papillomavirus 16 , Human papillomavirus 18 , Laryngeal Neoplasms , Lymph Nodes , Neck , Neoplasm Metastasis , Polymerase Chain ReactionABSTRACT
Objective:To evaluate the role of human papillomavirus(HPV)16/18E6,cyclin D1,and human telomerase transcriptase(hTERT)in the development of laryngeal carcinoma by detecting the expression of these three genes.Methods:Immunohistochemistry was used to detect the levels of HPV16/18E6,cyclin D1,and hTERT in 42 cases of paraffin-embedded tissues.Results:(1)The positive expression ratios of HPV16/18E6,cyclinD1,and hTERT in the laryngeal carcinoma group were 42.9%(18/42),50%(21/42),and 83.3%(35/42),respectively.These values were significantly higher than that in the control group.(2)The increase in the expression of HPV16/18E6 and cyclinD1 was associated with T stage advance and lymph node metastases.The expression of hTERT increased along with T stage advance,but not with lymph nodes metastases.The changes in the expression of HPV16/18E6,cyclinD1,and hTERT were not associated with gender and age.(3)Positive correlation was observed between HPV16/18E6 and cyclinD1 as well as between HPV16/18E6 and hTERT in laryngeal carcinoma.Conclusion:(1)The expression of HPV16/18E6,cyclin D1,and hTERT may be associated with the development of laryngeal carcinoma.(2)There may be interactions between HPV16/18E6 and cyclinD1,between HPV16/18E6 and hTERT.These interactions may induce the development of laryngeal carcinoma.The information provided by this study may be important for further investigation into the relationship between HPV16/18 and laryngeal carcinoma.