• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.3997-4003
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• 2014

Background: Infection with certain human papillomavirus (HPV) genotypes is the most important risk factor related with cervical cancer. The objective of the present study was to investigate the prevalence of HPV infection, the distribution of HPV genotypes and HPV E6/E7 oncogene mRNA expression in Turkish women with different cervical cytological findings in Mersin province, Southern Turkey. Materials and Methods: A total of 476 cytological samples belonging to women with normal and abnormal cervical Pap smears were enrolled in the study. For the detection and genotyping assay, a PCR/direct cycle sequencing approach was used. E6/E7 mRNA expression of HPV-16, 18, 31, 33, and 45 was determined by type-specific real-time NASBA assay (NucliSENS EasyQ$^{(R)}$HPV v1.1). Results: Of the 476 samples, 106 (22.3%) were found to be positive for HPV DNA by PCR. The presence of HPV was significantly more common (p<0.001) in HSIL (6/8, 75%) when compared with LSIL (6/14, 42.9%), ASC-US (22/74, 29.7%) and normal cytology (72/380, 18.9%). The most prevalent genotypes were, in descending order of frequency, HPV genotype 66 (22.6%), 16 (20.8%), 6 (14.2%), 31 (11.3%), 53 (5.7%), and 83 (4.7%). HPV E6/E7 oncogene mRNA positivity (12/476, 2.5%) was lower than DNA positivity (38/476, 7.9%). Conclusions: Our data present a wide distribution of HPV genotypes in the analyzed population. HPV genotypes 66, 16, 6, 31, 53 and 83 were the predominant types and most of them were potential carcinogenic types. Because of the differences between HPV E6/E7 mRNA and DNA positivity, further studies are required to test the role of mRNA testing in the triage of women with abnormal cervical cytology or follow up of HPV DNA positive and cytology negative. These epidemiological data will be important to determine the future impact of vaccination on HPV infected women in our region.

• BMB Reports
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• 제49권8호
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• pp.431-436
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• 2016

Human papillomavirus (HPV) is the major cause of cervical cancer, a deadly threat to millions of females. The early oncogene product (E7) of the high-risk HPV16 is the primary agent associated with HPV-related cervical cancers. In order to understand how E7 contributes to the transforming activity, we investigated the structural features of the flexible N-terminal region (46 residues) of E7 by carrying out N-15 heteronuclear NMR experiments and replica exchange molecular dynamics simulations. Several NMR parameters as well as simulation ensemble structures indicate that this intrinsically disordered region of E7 contains two transient (10-20% populated) helical pre-structured motifs that overlap with important target binding moieties such as an E2F-mimic motif and a pRb-binding LXCXE segment. Presence of such target-binding motifs in HPV16 E7 provides a reasonable explanation for its promiscuous target-binding behavior associated with its transforming activity.

• 대한의생명과학회지
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• 제29권3호
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• pp.144-151
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• 2023

A Pap smear is the most important screening test for the diagnosis of cervical cancer. However, subjective judgment by the operator cannot be excluded, and replicability may greatly be reduced if uncertain specimens are examined. Examiners often experience difficulties in differentiating atrophy with inflammatory changes and ASCUS when diagnosing squamous epithelial lesions from a pap smear. Reports often vary between cytologists and pathologists, and misdiagnosis may result in delayed follow-ups and advanced diseases. Hence, auxiliary examinations are necessary when confusing results between atrophy and ASCUS are obtained. The importance of p16^INK4a activation due to HPV infection, which is an important factor in the outbreak of cervical cancer, has been highlighted. Recent studies have reported that p16^INK4a immunocytochemical staining and HPV high-risk type tests using liquid-based cervical specimens are effective to detect the presence of lesions of grade HSIL or higher in patients with ASC-H. However, no research exists on the utility of HPV and p16^INK4a tests on the differential diagnosis of atrophy and ASCUS. This study focused on whether p16^INK4a immunocytochemical staining and HPV tests can help diagnose borderline lesions between atrophy and ASCUS. The results reported that p16^INK4a activation can significantly (P<0.001) differentiate atrophy from ASCUS in atrophic lesions infected with High risk-HPV. Therefore, it may be concluded that p16^INK4a immunocytochemical staining is an effective auxiliary test in lesions infected with HR-HPV when atrophic lesions are difficult to differentiate by morphology. Such results are expected to help decide on adequate follow-up and treatment.

• 생명과학회지
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• 제19권2호
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• pp.234-240
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• 2009

부산지역의 유흥업소 종사여성을 대상으로 HPV DNA chip 시험을 통하여 HPV 유병율 및 유전자형 분포를 조사하였다. 총 660건의 자궁경부도찰 검체로부터 258건(양성율 39.1%)이 검출되었으며, 20대에서 가장 높은 유병율을 나타내었다. 양성자의 유전자형 분포는 고위험군 유전자형의 경우 HPV-16 (15.9%), -53 (10.2%), -58 (7.7%), -18 (5.2%)순이었고, 저위험군 유전자형의 경우 HPV-70 (10.4%), -6 (4.1%), -11 Journal of Life Science 2009, Vol. 19. No. 2 239 (2.0%)순이었다. 특이하게 고위험군 감염여성의 분포비(62.0%)가 저위험군(14.7%) 및 고/저위험군 혼합감염(12.0%)보다 4배 가까이 높았다. 전체 양성자중 단일유형 감염자는 175건(67.8%)이고 혼합유형 감염자는 83건(32.2%)이었다. 본 연구 결과 밝혀진 부산지역 유흥업소 종사여성에서 많이 발견되는 HPV 유전자형 분포의 다양성은 국내 도입된 자궁경부암 예방백신의 효과 예측 및 국내 특성에 맞는 다가백신 개발의 기초 자료가 될 수 있을 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4297-4302
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• 2015

Background: To evaluate HPV testing by Hybrid Capture II (HCII) in conjunction with cytology in detecting the residual/recurrence disease after treatment of high-grade cervical intraepithelial neoplasia (CIN II-III) with loop electrosurgical excision procedure (LEEP). Materials and Methods: A retrospective review of 158 patients with histologically confirmed CIN II-III who underwent LEEP between January 2011 and October 2012 was conducted. Post-treatment control was scheduled at the 3rd, 6th, 12th and 18th month. All patients were followed up by Pap smear and HR-HPV genotype and viral load testing. Results: Pre-treatment, HR-HPV DNA, was detected in all specimens of the patients. At follow-up, 25 patients were diagnosed as the residual/recurrent disease during the FU visit, among whom, 16 patients with positive margin: 13 patients (52%) with HR-HPV DNA+/cytology+, 2 patients (8%) with HR-HPV DNA+/cytology-, 1 patient (4%) with cytology+/HR-HPV DNA-; 9 patients with clean margin - 5 patients (55.6%) with HR-HPV DNA+/cytology+; 2 patients (22.2%) with HRHPV DNA+/cytology-, 2 patients (22.2%) with cytology+/HR-HPV DNA-. None of them persisting HR-HPV DNA-/cytology-with positive or negative margin was identified as the residual/recurrent disease. The majority of residual/recurrent disease was detected at the 12th and 18th month FU, and there was almost no difference in the sensitivity and negative predictive value (NPV) between at the 3rd month and the 6th month FU visits. 14 residual/recurrence disease (14/46:30.4%) had pre-treatment high viral load (>5 000 RUL/PC) and 11 (11/112, 9.8%) with pre-treatment low viral load, P<0.05. Conclusions: (1) The persistence HR-HPV DNA is the root cause of the residual/recurrent disease for the women treated for high-grade CIN; the pre-treatment viral load and margin can be seen as the predictor. (2) The FU visit beginning at the 6th month post-treatment and lasting at least 24 months with the combination of cytology and HPV testing. (3) Patients with high pre-treatment HPV load, which is considered as one risk of developing the residual/recurrent disease, should be paid more attention (especially above 500RUL/PC) to by clinicians.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2355-2359
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• 2013

Vulva cancer is rare among all gynecological cancer worldwide, including Thailand, and mainly affects older women. Persistent high risk type infection of human papillomavirus (HPV) is the one important factor for developing cancer. In this study, we focused on HPV DNA investigation and type-specific distribution of HPV in 25 formalin-fixed paraffin-embedded (FFPE) samples collected from Thai women with vulva cancer histologically confirmed by the National Cancer Institute, Thailand, during 2003-2011. HPV DNA detection and genotyping were undertaken with polymerase-chain reaction and enzyme-immunoassay using GP5+/bio6+ consensus specific primers and digoxigenin-labeled specific oligoprobes, respectively. Human ${\beta}$-globin genes was used as the internal control. Our results showed that 44% (11/25) of all vulva cancer samples were HPV-positive. All of them are high risk HPV type infection, detected as single (63.64%, 7/11) and/or double infections (4/11, 36.36%). HPV 16 was the most common type identified in vulva cancer, followed by HPV 35, 33, 18 and 58. In conclusion, this study presented that HPV-16 is observed at the highest frequency in this cancer, similar to cervical cancer, with HPV 18 being less frequent. Although the sample size was small and could not represent overall incidence and prevalence in Thai women, these preliminary data for vulva cancer are of interest since they reinforce the necessity for HPV screening or vaccination in Thailand.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5439-5444
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• 2012

Objective: To explore the correlation of human papillomavious (HPV) infection with expression of p53 and proliferating cell nuclear antigen (PCNA) in patients with different ethnicity in Xinjiang, China. Methods: 166 biopsy specimens from 83 laryngeal squamous cell carcinomas (LSCC), 63 laryngeal papillomas (LP), and 20 laryngeal inflammatory polyps (LIP) were included in this study. HPV infection was determined by polymerase chain reaction (PCR) using specific types of HPV primers. Expression of p53 and PCNA was assessed using immunohistostaining. Results: The frequency of HPV 6/11 was higher in LP (33.3%) than in LSCC (9.6%) (P<0.0005), whereas the frequency of HPV 16/18 was higher in LSCC (37.3 %) than in LP (6.3%) (P<0.0005). Patients of the Han ethnic group with LSCC had a higher infection rate with HPV 6/11 or HPV 6/11 and HPV 16/18 coinfection than those of Uygur and Kazak ethnicity (P<0.05). Overexpression of p53 and PCNA were higher in LSCC (62.7%, 57.8%) than in LP (38%, 33.3%) (P<0.005, and P<0.005, respectively). That of p53 was not associated with lymph-node metastases and clinical stages, but overexpression of PCNA closely correlated with clinical stage. Conclusions: These results strongly implicate HPV6/11 infection in the carcinogenesis of LSCC and LP, respectively. There was a higher coincidence of increased malignancy of laryngeal tumors with overexpression of p53 and PCNA. Overexpression of p53 may serve as an early risk marker for malignant transformation in HPV infected cells while the overexpression of PCNA may serve as a late marker for progression of LSCC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2299-2304
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• 2012

Since there is evidence that human papillomavirus (HPV) may play some role in oral carcinogenesis, we investigated the presence of HPV in a group of Pakistani subjects with normal oral cavity using real-time PCR analysis. Two-hundred patients attending the Dental Department, Sandaman Provincial Hospital, Balochistan, Pakistan, were recruited. After interview, oral epithelial cells were collected by scraping and subjected to DNA extraction. The HPV-positive DNA samples were further analyzed using primer sets specific for HPV-16 and -18. It was found that out of 200 DNA samples, 192 were PCR-positive for the ${\beta}$-globin gene and these were subsequently examined for the presence of HPV DNA. Among these, 47 (24.5%) were HPV-positive with the virus copy number ranged between 0.43-32 copies per 1 ${\mu}g$ of total DNA (9-99 copies per PCR reaction). There were 4 and 11 samples containing HPV-16 and -18, respectively. Additionally, one sample harbored both types of HPV. Among the investigated clinical parameters, smoking habit was associated with the presence of HPV (p = 0.001) while others indicated no significant association. The prevalence of HPV in normal oral cavity in our Pakistani subjects appears to be comparable to other studies. However, the association between the presence of HPV and smoking warrants further investigations whether both of these factors can cooperate in inducing oral cancer in this group of patients.

• 대한기관식도과학회지
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• 제5권1호
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• pp.49-54
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• 1999

The etiology of inverted papilloma(IP) remains unknown, but several studies have reported that Human Papillomavirus(HPV) may play a role in the pathogensis of sinonasal inverted papilloma(IP). And recent reports demonstrate the possible etiologic role of Epstein-Barr virus (EBV) in sinonasal IP. The aim of this study is to detect HPV and EBV in sinonasal IP, to examine the relationship between HPV subtype and sinonasal IP, to investigate the relation between HPV and EBV. We reviewed 30 cases of sinonasal IP(simple IP 19 cases, IP with dysplasia 8 cases, IP with squamous cell carcinoma 3 cases). Paraffin embedded archival tissue was used in this study. Detection of HPV, EBV were examined by in situ hybridization(ISH) using HPV type 6/11, 16/18, 31/33/35 DNA probe and EBER probe. The HPV was detected in 6(20%) out of 30 cases. The HPV 6/11 was dectected in 4 out of 19 cases of simple IP, HPV 16/18 in 1, HPV 31/33/35 in 1 out of 8 cases of IP with dysplasia respectively. The EBV was not detected in 30 cases. HPV may play a role in the pathogensis of sinonasal inverted papilloma. But EBV is not a etiopathologic factor to be considered in the development of sinonasal IP.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제39권5호
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• pp.224-230
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• 2013

Objectives: Papilloma frequently develops as a benign tumor of the head and neck area, but its potential for malignant transformation has yet to be studied. This study aims to provide basic information for papillomas using the immunohistochemical staining of matrix metalloproteinase 2 (MMP-2) and human papilloma virus (HPV) 16 and 18. Materials and Methods: To evaluate the malignant transformation of papillomas, the selected tissue samples were serially diagnosed with pre-cancerous papilloma (with epithelial dysplasia, pseudo-epitheliomatous hyperplasia) or malignant lesion (squamous cell carcinoma, SCC) after the first diagnosis (squamous papilloma, inverted papilloma). The selected tissues were stained with an antibody to MMP-2 and HPV 16-E7, HPV 18-L1. A statistical analysis was performed according to each transformation step. Results: The epithelial layer of papilloma and pre-cancerous papilloma lesions had a similar MMP-2 expression, but that of the malignant lesion had a significantly increased MMP-2 expression. HPV 16 and 18 infection rates were 28.6%, 33.3% and 63.6% in papillomas, pre-cancerous papilloma lesions, and SCC. Conclusions: A relatively high MMP-2 expression and HPV 16 or 18 infection of papillomas may be associated with early events in the multistep processes of malignant transformation of papillomas.