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

• Korean Journal of Clinical Laboratory Science
• /
• v.49 no.4
• /
• pp.446-454
• /
• 2017

Human papillomaviruses (HPVs) are major causes of cervical cancer. Sixteen high risk HPVs, including HPV 16, HPV 18, HPV31, HPV 33, HPV 35, HPV 39, HPV 45, HPV 51, HPV 52, HPV 53, HPV 56, HPV 58, HPV 59, HPV 66, HPV 68, and HPV 69 are found in cervical cancer. HPVs 16 and 18 are mainly presented in 70% of cervical cancer. Therefore, identifying the presence of these high-risk HPVs is crucial. The objective of this study is to establish the HPV ViroCheck for detecting 16 HR-HPVs and genotypes of HPVs 16 and 18, as well as to analyze the analytical performance of HPV ViroCheck. We performed the analytical sensitivity of HPV E6 / E7 genes of 16 high risk HPVs to confirm the limit of detection. Then, a cross reactivity of HPV ViroCheck with microorganisms and viruses related to the cervix were analyzed for analytical specificity. Analytical sensitivity of high risk HPV genotypes ranged from 1 to 100 copies when using cloned DNAs. The limit of detection was 10 cells for both SiHa and HeLa cells. Cervical-related microorganisms and viruses did not show cross-reactivity to HPV DNA. Moreover, the intra- and inter-assay coefficient variations (CVs) were below 5%. In conclusion, HPV Virocheck will be useful for the detection of 16 HR HPVs, as well as HPV 16 and HPV 18 genotypes rapidly.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.9
• /
• pp.4989-4992
• /
• 2013

Aim: To compare p16INK4a immunocytochemistry with the HPV polymerase chain reaction in predicting high grade cervical squamous intraepithelial lesions. Materials and Methods: This diagnostic case-control study was conducted from January 2010 until December 2010. We obtained 30 samples, classified according to the degree of cervical intraepithelial neoplasia (CIN): 11 samples for CIN 1, 9 samples for CIN 2, and 10 samples for CIN 3. HPV PCR, p16INK4a immunocytochemistry, and histopathological examination were performed on all samples. Statistical analysis was conducted using SPSS 20.0. Results: In predicting CIN 2-3, we found p16INK4a to have similar specificity and positive predictive value as HPV PCR (95%, 97.2% vs 96.7%), but better sensitivity (87.5% vs 72.5%) and negative predictive value (82.1% vs 67.6%). The most prevalent types of high-risk HPV in our study were HPV 33, 35, 58, 52, and 16. Conclusions: p16INK4a has better diagnostic values than HPV PCR and may be incorporated in the triage of ASCUS and LSIL to replace HPV PCR. Genotype distribution of HPV differs in each region, providing a challenge to develop HPV vaccines based on the epidemiology of HPV in that particular region.

• Korean Journal of Head & Neck Oncology
• /
• v.27 no.1
• /
• pp.17-21
• /
• 2011

연구 및 목적 : 이번 연구의 목적은 한국인에서 편도 편평세포암종의 발생에 고위험 인간유두종 바이러스(high risk human pap-illomavirus)의 역할 및 관여 인자에 대해 밝히고자 한다. 재료 및 방법 : 연구는 편도 편평상피세포암종으로 진단받은 54명을 대상으로 하였다. 고위험 인간유두종 바이러스의 감염을 알기위해 in situ hybridization 방법을 이용하였다. 고위험 인간유두종 바이러스의 감염과 나이, 성별, 흡연, 음주, 병기, 병리학적 특징 등과의 관계를 분석하였다. 결 과 : 고위험 인간유두종 바이러스의 양성율은 31.5%(17/54)였다. 고위험 인간유두종 바이러스 감염은 젊은 연령(50세 미만), 비흡연자, 림프절 전이와 유의한 상관관계가 있었다(각각 p=0.008, p=0.042, p=0.027). 하지만 성별, 음주, 원발부위 병기, 종양분화도, 피막외침범, 혈관 및 신경 침범과 고위험 인간유두종 바이러스와의 관계는 통계적으로 유의하지 않았다. 6개월 이상 추적 관찰이 가능한 환자를 대상으로 조사한 5년 전체 생존율 및 질병 특이 생존율은 각각 60%와 62%였다. 고위험 인간유두종 바이러스의 양성율은 질병 특이 생존율과 유의한 상관관계가 있었다(p=0.019). 결 론 : 한국인의 고위험 인간유두종 바이러스 감염은 젊은 연령 및 비흡연자의 편도 편평세포암종의 발생에 관련이 있고 예후 인자로 중요한 역할을 한다.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.14
• /
• pp.5843-5846
• /
• 2015

Background: Detection of cervical high grade lesions in patients with atypical squamous cells of undetermined significance (ASCUS) is still a challenge. Our study tested the efficacy of the paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in ASCUS and compared performance with the hybrid capture 2 (HC2) human papillomavirus (HPV) test. Materials and Methods: A total of 463 consecutive ASCUS women from primary screening were selected. Their cervical scrapings were collected and assessed by PAX1 methylation analysis (MS-HRM) and high-risk HPV-DNA test (HC2). All patients with ASCUS were admitted to colposcopy and cervical biopsies. The Chisquare test was used to test the differences of PAX1 methylation or HPV infection between groups. Results: The specificity, sensitivity, and accuracy for detecting CIN2 + lesions were: 95.6%, 82.4%, and 94.6%, respectively, for the PAX1 MS-HRM test; and 59.7%, 64.7%, and 60.0% for the HC2 HPV test. Conclusions: The PAX1 methylation analysis by MS-HRM demonstrated a better performance than the high-risk HPV-DNA test for the detection of high grade lesions (CIN2 +) in ASCUS cases. This approach could screen out the majority of low grade cases of ASCUS, and thus reduce the referral rate to colposcopy.

• Biomedical Science Letters
• /
• v.11 no.1
• /
• pp.51-56
• /
• 2005

The detection of high-risk human papilloma virus (HPV) allows us to predict the presence and future development of cervical intraepitheliallesion. In this study, we compared Hybrid Capture II and DNA chip methods for detection of HPV in cervical swab samples. And we evaluated the clinical efficacy and diagnostic performance of HPV DNA chip and Hybrid Capture II for detecting HPV in cervical neoplastic lesions. Seventy four patients were classified into three groups according to their histologic diagnosis: Group I (nonspecific chronic cervicitis), Group II (low-grade squamous intraepithelial lesion (SIL); koilocytosis, and mild dysplasia), and Group III (high-grade SIL;, moderate, severe dysplasia and in situ carcinoma). Cytologic diagnosis were based on the Bethesda System. Hybrid Capture II and DNA chip methods were performed to detect HPV. In 41 of the 74 cervical samples $(55.4\%)$, HPV DNAs were detected by Hybrid Capture II. In Group III, HPV-positive cases were detected in 15 $(20.3\%)$ of 74 patients by Hybrid Capture II. 25 patients with ASCUS cytology were histopathologically examined: 9 cases $(36\%)$ were Group II. In 18 patients with low-grade SIL cytology, 13 cases $(72.2\%)$ were Group II and 3 cases $(16.7\%)$ were Group III. 12 cases $(92.3\%)$ were Group ill of 13 patients with high-grade SIL cytology. The sensitivity of each test was $82\%$ in Hybrid Capture II and $53.9\%$ in DNA chip test. And the specificity was $74.3\%,\;85.7\%$ in Hybrid Capture II and DNA chip. In conclusion, Hybrid Capture II test is more sensitive than DNA chip in detecting women with cervical neoplastic lesions. Especially, in diagnosing of ASCUS, Hybrid Capture II test is more sensitive. Therefore, Hybrid Capture II test for cancer-associated HPV DNA is a viable option in the management of women with ASCUS.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.1
• /
• pp.511-514
• /
• 2013

Background: A small but significant proportion of cases with atypical squamous cells of undetermined significance (ASCUS) may harbour CIN 2-3, or even invasive carcinoma. Although immediate colposcopy, HPV-DNA testing or expectant management are three recommended options in ASCUS triage, a consensus does not currently exist on which one of these approaches is the most efficient. In this study, we aimed to compare the performance and cost of immediate colposcopy and colposcopy based on the human papillomavirus (HPV) testing for detecting histologically confirmed high-grade cervical intraepithelial neoplasia (CIN) in women with ASCUS. Materials and Methods: Records of 594 women with an index Papanicolaou smear showing ASCUS were retrospectively analyzed. Women in the immediate colposcopy arm were referred directly to colposcopy (immediate colposcopy group, n=255) and those in the HPV triage arm were proceeded to colposcopy if the high-risk HPV (hrHPV) test was positive (HPV triage group, n=339). High grade CIN (CIN2+) detection rate and treatment costs were compared between the groups. Results: The detected rate of CIN2+ was higher in the HPV triage group compared to immediate colposcopy group (8% vs. 1.6%, p=0.011). In the HPV triage group, the total cost, cost per patient, and the cost for detecting one case of high grade CIN were higher than the immediate colposcopy group (p<0.001). Conclusions: In women with ASCUS cytology, HPV DNA testing followed by colposcopy is more costly than immediate colposcopy, but this approach is associated with a higher rate of CIN2+ detection. This findings suggest that HPV DNA testing combined with cervical cytology could reduce the referral rate to colposcopy.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.14
• /
• pp.5993-5999
• /
• 2015

Background: Molecular testing for human papillomavirus (HPV) is the most objective and reproducible of all cervical cancer screening tests and also less demanding in terms of training and quality assurance. However, there is an impending need for cost effective molecular HPV testing methods with sampling ease, easy storage measures and minimum turn around times suitable for a low resource setting. Objective : Our aim was to evaluate the feasibility of using a fast transfer analysis (FTA) mini elute cartridge for cervical sampling to identify high risk HPV by real time PCR and to compare molecular HPV testing and Pap cytology testing to predict histologically confirmed cervical precancer (CIN 2+ lesions) in a cervical cancer prevention program. Materials and Methods: This was conducted as a pilot study (n=200) on women sampled using FTA mini elute cartridges, genotyped by two different real time PCR assays, detecting 13 high risk HPV (HR HPV) species, including HPV16 along with its physical DNA status. Results obtained from each of the tests were compared and analysed using suitable statistical tests. Results: With FTA mini elute cartridge samples HR HPV positivity was seen in 48/200 (24%). Of these, presence of HPV 16 DNA was observed in 28/48 (58.3%) women. High risk HPV was positive in 20% (37/185) of women with benign cytology and 73.3% (11/15) of women with abnormal cytology findings. A very significant correlation (${\chi}^2=22.090$ ; p=0.000) was observed between cytology and HR HPV findings showing an increasing trend of HR HPV prevalence in 50% (1/2) of LSIL, 75% (3/4) of HSIL and 100% (3/3) of SCC. Of the CIN 2+ lesions identified by histopathology, 88.9% (8/9) had HR HPV. A significant association (${\chi}^2=11.223$ ; p=0.001) of HR HPV and histopathologically confirmed CIN 2+ lesions was found. Sensitivity of the two tests were comparable but specificity of Pap testing was better (90.7% vs 70.4%) to predict histopathologically diagnosed cervical precancers. Conclusions: The current study explored the feasibility of using a FTA mini elute cartridge for cervical sampling for the first time in India as a part of a community based cervical cancer prevention program. We suggest that FTA based sampling is suitable and feasible for real time based HPV testing. Molecular HR HPV testing can be more sensitive and useful to identify high risk women requiring Pap testing which is more specific to detect histologically confirmed cervical precancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.15
• /
• pp.6521-6526
• /
• 2015

Background: This study aimed toanalyze the risk behavior for cervical cancer (CC) and the human papillomavirus (HPV) prevalence and resolution among women who received care through the private healthcare network of a municipality in southern Brazil. Materials and Methods: This descriptive and retrospective study was conducted with 25 women aged 20 to 59 years who received care through the private healthcare network and were treated at a specialty clinic in the period from January to December 2012 in a municipality in Northwest Parana, Southern Brazil. Data from medical records with cytological and HPV results were used. Following treatment, these women were followed-up and reassessed after 6 months. Data were statistically analyzed using the t-test and chi-squared test at a 5% significance level. Results: The mean age of the studied women was $27.8{\pm}7.75$ years old, and the majority were married, with paid employment and were non-smokers. The mean age at menarche was $13.0{\pm}0.50$ years old, and the mean age at first intercourse was $17.5{\pm}1.78$ years, with only 8.0% (2) initiating sexual activity at an age ${\leq}15$ years old. The majority had 1 to 2 children (60.0%), while 88.0% reported having had one sexual partner in their lifetime, and all the women were sexually active. A total of 68.0% used a hormonal contraceptive method. All the women had leukorrhea and pain and were infected by a single HPV type. Regarding the lesion grade, 80.0% showed high risk and 20.0% low risk. The most prevalent high-risk HPV strain was 16. Conclusions: These findings provide relevant information on HPV risk factors and infection, as well as the treatment and 6-month follow-up results, in economically and socially advantaged women with no traditional risk factors, corroborating previous reports that different risk factors may be described in different populations. Thus, this study reinforces the fact that even women without the traditional risk factors should undergo HPVmonitoring and assessment to determine the persistence of infection, promoting early diagnosis of the lesions presented and appropriate treatment to thus prevent the occurrence of CC.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.12
• /
• pp.6109-6113
• /
• 2012

Background: Oral cancer has become one of the most prevalent cancers worldwide and human Papillomavirus is one of the risk factors for developing oral cancer. For this study HPV18 was chosen as it is one of the high risk HPV types and may lead to carcinogenesis. However, prevalence of HPV18 infection in Oral Squamous Cell Carcinoma in Malaysia remains unclear. Objective: This study aimed to investigate the viral load of HPV18 DNA in OSCC and potentially malignant lesions using saliva samples. Materials and Methods: Genomic DNAs of thirty saliva samples of normal subjects and thirty saliva samples compromised of 16 samples from potentially malignant lesions and 14 of OSCC patients were amplified for HPV18 DNA using a nested polymerase chain reaction analysis. All PCR products were then analyzed using the Bioanalyzer to confirm presence of HPV18 DNA. Result: From thirty patients examined, only one of 30 (3.3%) cases was found to be positive for HPV18 in this study. Conclusion: The finding of this study revealed that there is a low viral detection of HPV18 in Malaysian OSCC by using saliva samples, suggesting that prevalence of HPV18 may not be important in this group of Malaysian OSCC.