• 생명과학회지
• /
• 제24권9호
• /
• pp.1025-1029
• /
• 2014

자궁경부암은 전세계 여성의 사망원인 2위를 차지하며, 인유두종바이러스 감염과 상관성이 있다. 인유두종바이러스의 백신정책, 병인론, 추적관찰, 역학에서 유전형 검사는 중요하다. 후향적 연구를 위하여 파라핀 조직에서 역교잡반응을 이용하여 인유두종바이러스의 유전형을 검사하는 것은 명확하게 증명된 것은 아니다. 본 연구에서는 자궁경부암 파라핀 조직에서 역교잡반응을 사용하여 인유두종바이러스의 유전형 검사의 유용성을 평가하였다. 총 52개의 자궁경부암 파라핀 조직을 사용하여 역교잡반응을 실시하여 인유두종바이러스의 유전형을 검출하였다. 52개의 파라핀 조직중에서 32(61.5%) 건에서 인유두종바이러스가 검출되었으며, 단순감염이 27(84.4%) 건, 복합감염이 5(15.6%) 건으로 검출되었다. 단순감염에서 인유두종바이러스 유전형은 고위험군 18(8), 58(6), 16(5), 33(1), 35(1), 39(1), 56(1) 유전형과, 저위험군 11(2), 6(1), 70(1) 유전형으로 분석되었다. 복합감염에서 인유두종바이러스 유전형은 16/18(2), 18/52(1), 16/56(1), 16/18/33(1) 유전형으로 검출되었다. 본 연구를 통하여, 파라핀 조직으로 후향적 연구를 위한 인유두종바이러스 유전형 검사가 가능할 것으로 기대된다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권3호
• /
• pp.1129-1134
• /
• 2016

Vulva and Vaginal cancers are rare among all gynecological cancers worldwide, including Thailand, and typically affect women in later life. Persistent high risk human papillomavirus (HR-HPV) infection is one of several important causes of cancer development. In this study, we focused on HPV investigation and specific type distribution from Thai women with abnormality lesions and cancers of the vulva and Vaginal. A total of ninety paraffin-embedded samples of vulva and Vaginal abnormalities and cancer cells with histologically confirmed were collected from Thai women, who were diagnosed in 2003-2012 at the National Cancer Institute, Thailand. HPV DNA was detected and genotyped using polymerase chain reaction and enzyme immunoassay with GP5+/bio 6+ consensus specific primers and digoxigenin-labeled specific oligoprobes, respectively. The human ${\beta}$-globin gene was used as an internal control. Overall results represented that HPV frequency was 16/34 (47.1%) and 8/20 (40.0%) samples of vulva with cancer and abnormal cytology lesions, respectively, while, 3/5 (60%) and 16/33 (51.61%) samples of Vaginal cancer and abnormal cytology lesions, respectively, were HPV DNA positive. Single HPV type and multiple HPV type infection could be observed in both type of cancers and abnormal lesion samples in the different histological categorizes. HPV16 was the most frequent type in all cancers and abnormal cytology lesions, whereas HPV 18 was less frequent and could be detected as co-infection with other high risk HPV types. In addition, low risk types such as HPV 6, 11 and 70 could be detected in Vulva cancer and abnormal cytology lesion samples, whereas, all Vaginal cancer samples exhibited only high risk HPV types; HPV 16 and 31. In conclusion, from our results in this study we suggest that women with persistent high risk HPV type infection are at risk of developing vulva and Vaginal cancers and HPV 16 was observed at the highest frequent both of these, similar to the cervical cancer cases. Although the number of samples in this study was limited and might not represent the overall incidence and prevalence in Thai women, but the baseline data are of interest and suggest further study for primary cancer screening and/or developing the efficiency of prophylactic HPV vaccines in Thailand.

• Tuberculosis and Respiratory Diseases
• /
• 제71권5호
• /
• pp.349-354
• /
• 2011

Background: Lung cancer is the leading cause of cancer deaths in the world. Human papillomavirus (HPV) infection and E6 oncoprotein expression are known risk factors for the development of non-small cell lung cancer (NSCLC). This study was performed to evaluate the prevalence of HPV 16/18 E6 oncoprotein expression in patients with NSCLC. Methods: Immunohistochemical stains of the HPV 16/18 E6 oncoprotein were performed in tumor tissues from 68 patients with NSCLC who underwent curative surgery from March 2006 to November 2008. Results: The E6 oncoprotein was expressed in 29.4% of patients with NSCLC and a statistical analysis revealed that E6 oncoprotein expression was significantly higher in females (p=0.028), never smokers (p=0.045), and patients with adenocarcinoma (p=0.022) than that in other patients. Conclusion: The E6 oncoprotein was expressed in 29.4% of patients with NSCLC. Further studies detecting HPV infection and E6 oncoprotein expression in never smoking patients with NSCLC are needed.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제33권5호
• /
• pp.548-553
• /
• 2007

Several investigators have shown that human papillomavirus(HPV) appear to play an etiologic role in oral and paranasal sinus carcinoma. It was known that 15-25% of head and neck squamous cell carcinoma(SCC) showed HPV-positive infection. Among them, HPV 16 was the most common type but HPV 18 was observed only 2-4% of HPV-positive head and neck cancers. In recent, we treated uncommon 2 oral SCC cases that associated with HPV infection. One is a case of tongue SCC after bone marrow transplantation(BMT), and the other is a case of SCC occurring with aspergillosis in the maxillary sinus. After surgery, HPV 16 and 18 were detected in the surgical specimens by the histological and polymerase chain reaction(PCR) examination. In this report, we present these cases with a review of literature.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권17호
• /
• pp.7395-7399
• /
• 2014

Background: Persistent human papillomavirus (HPV) infection, especially with high-risk types such as HPV16 and HPV18, has been identified as the primary cause of cervical cancer. E6 and E7 are the major onco-proteins of high-risk HPVs, which are consistently expressed in HPV infected tissues but absent in normal tissues and represent ideal therapeutic targets for immunotherapy of cervical cancer. Materials and Methods: In this study, the optimized fusion gene HPV18 E6E7 (HPV18 ofE6E7) was constructed according to genetic codon usage for human genes. At the same time, for safety future clinical application, a mutant of HPV18 ofE6E7 fusion gene was generated by site-directed mutagenesis at L52G for the E6 protein and C98G for the E7 protein. Results: HPV18-E6E7 mutant (HPV18 ofmE6E7) constructed in this work not only lost the transformation capability for NIH 3T3 cells and tumorigenicity in BALB/c nude mice, but also maintained very good stability and antigenicity. Conclusion: These results suggest that the mutant should undergo further study for application as a safe antigenspecific therapeutic vaccine for HPV18-associated tumors.

• 대한의생명과학회지
• /
• 제25권4호
• /
• pp.390-397
• /
• 2019

High risk-human papillomavirus (HR-HPV) is known to be a major cause of cervical cancer, and coinfection of sexually transmitted pathogen (STP) has been reported to cause persistent HPV infection. However, the relationship between HPV and STP coinfection remains unclear. The purpose of this study was to analyze the coinfection rate with STP in high-risk human papillomavirus infected women in Busan and to collect basic data for the prevention of cervical lesions. This study was carried out in 355 women who had concurrent HPV and STP screening at Busan local hospital between January 2016 and December 2017. HPV and STP coinfection was found in 187 (52.7%) out of 355 cases. HR-HPV and STP coinfection was 82.9% higher than LR-HPV and STP coinfections 17.1%. In HR-HPV infection, Ureaplasma species was the most common pathogen (47.1%), followed by C. trachomatis (21.9%) and Mycoplasma species (12.3%). In the analysis of HR-HPV genotype according to STP, HPV 16 (12.0%) was the most frequent, followed by HPV 58 (11.6%), HPV 39 (11.1%) and HPV 52 (10.2%), but HPV 18 showed a low coinfection rate of 1.3%. According to the results of age, HR-HPV and STP coinfection rate was the highest at 41.9% among women aged 18 to 29. HR-HPV and Ureaplasma species showed the highest coinfection rates at all ages, followed by C. trachomatis and Mycoplasma species. Further studies with more samples will be needed to determine if the coinfection of HR-HPV and STPs is involved in the development of cervical tumors through histologic changes.

• BMB Reports
• /
• 제51권11호
• /
• pp.584-589
• /
• 2018

Secondary prevention via earlier detection would afford the greatest chance for a cure in premalignant lesions. We investigated the exomic profiles of non-malignant and malignant changes in head and neck squamous cell carcinoma (HNSCC) and the genomic blueprint of human papillomavirus (HPV)-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC). Whole-exome (WES) and whole-genome (WGS) sequencing were performed on peripheral blood and adjacent non-tumor and tumor specimens obtained from eight Korean HNSCC patients from 2013 to 2015. Next-generation sequencing yielded an average coverage of $94.3{\times}$ for WES and $35.3{\times}$ for WGS. In comparative genomic analysis of non-tumor and tumor tissue pairs, we were unable to identify common cancer-associated early mutations and copy number alterations (CNA) except in one pair. Interestingly, in this case, we observed that non-tumor tonsillar crypts adjacent to HPV-positive OPSCC appeared normal under a microscope; however, this tissue also showed weak p16 expression. WGS revealed the infection and integration of high-risk type HPV16 in this tissue as well as in the matched tumor. Furthermore, WES identified shared and tumor-specific genomic alterations for this pair. Clonal analysis enabled us to infer the process by which this transitional crypt epithelium (TrCE) evolved into a tumor; this evolution was accompanied by the subsequent accumulation of genomic alterations, including an ERBB3 mutation and large-scale CNAs, such as 3q27-qter amplification and 9p deletion. We suggest that HPV16-driven OPSCC carcinogenesis is a stepwise evolutionary process that is consistent with a multistep carcinogenesis model. Our results highlight the carcinogenic changes driven by HPV16 infection and provide a basis for the secondary prevention of OPSCC.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권23호
• /
• pp.10255-10262
• /
• 2015

High risk human papillomavirus (HR-HPV) E2 proteins play roles in transcriptional regulation and are commonly functionally disrupted when the HPV genome integrates into host chromosomes. Some 15-40% of cancer cases, however, contain an intact E2 gene or episomal HPV. In these cases, polymorphism of the E2 gene might be involved. This study aimed to determine polymorphisms of the E2 gene in episomal HPV16 detected in high grade squamous intraepithelial lesions and squamous cell carcinomas and altered functions compared to the E2 prototype. The E2 gene was amplified and sequenced. Two expression vectors containing E2 gene polymorphisms were constructed and transfected in SiHa and C33A cells, then E6 gene as well as Il-10 and TNF-${\alpha}$ expression was determined by quantitative RT-PCR. Expression vectors and reporter vectors containing the HPV16 long control region (LCR) were co-transfected and transcriptional activity was determined. The results showed that a total of 32 nucleotides and 23 amino acids were changed in all 20 cases of study, found in the transactivation (TA) domain, hinge (H) region and DNA binding (DB) domain with 14, 5 and 13 nucleotide positions. They mostly caused amino acid change. The expressing vectors containing different E2 gene polymorphisms showed E6 mRNA suppression, TNF-${\alpha}$ mRNA suppression and IL-10 induction but no statistically significant differences when compared to the E2 prototype. Moreover, promoter activity in HPV16 LCR was not affected by E2 protein with different gene polymorphisms, in contrast to nucleotide variations in LCR that showed an effect on transcription activity. These results demonstrated that E2 gene polymorphisms of episomal HPV16 did not affect transcriptional regulation and suggested that nucleotide variation as well as epigenetic modification of the LCR might play a role in inducing malignant transformation of cells containing episomal HPV16.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권2호
• /
• pp.693-697
• /
• 2015

Our aims were to evaluate the clinical performance of human telomerase RNA gene component (hTERC gene) amplification assay with high-risk human papillomavirus (HR-HPV) DNA test of Hybrid Capture 2 DNA test (HC2), for the detection of high grade cervical precancerous lesions and cancer (CIN 2+). In addition, the association shown between hTERC gene amplification and HPV DNA test positive in women with and without cervical neoplasia was assessed. There were 92 women who underwent cytology, HR-HPV DNA test, hTERC gene amplification test, colposcopy and biopsy. We compared the clinical performance of hTERC gene test along with HR-HPV DNA test of women with colposcopy and routine screening. The samples were histology-confirmed high-grade cervical intraepithelial neoplasia (CIN 2) or worse (CIN2+) as the positive criterion. The test of hTERC gene showed the hTERC gene amplification positivity increased with the severity of histological abnormality and cytological abnormality. The test of hTERC gene showed higher specificity than HR-HPV DNA test for high-grade lesions (84.4% versus 50%) and also higher positive predictive value (90.4% versus 76.5%). Our results predicted that hTERC gene amplification demonstrated more specific performance for predicting the risk of progression and offer a strong potential as a tool for triage in cervical cancer screening, with the limited sensitive as HR-HPV DNA test.

• 대한의생명과학회지
• /
• 제18권2호
• /
• pp.123-130
• /
• 2012

In this study, we evaluated the human papillomavirus (HPV) genotyping test called MolecuTech REBA HPV-$ID^{(R)}$ (YD Diagnostics, Seoul, Korea) for 704 women who also had cervical cytological evaluations by Thin Prep. The infection rate of high-risk HPV genotypes was 56.6% in patients with normal cytology, 59.8% in those with benign, low-grade squamous intraepithelial lesions, 51.4% in those with atypical squamous cells of uncertain significance, 92.3% in those with high-grade squamous intraepithelial lesions, and 94.1% in those with squamous cell carcinoma or adenocarcinoma. HPV 16 was the most common genotype detected in any lesion, followed by HPV 53, 58, 33, 52, 45, 31, and 35, in order. The HPV DNA test with PCR-REBA is a very highly sensitive, but less specific, method. The infection rates and HPV genotype distribution of non-Korean people versus people from South Korea showed regional differences.