• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.903-907
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• 2013

Primary screening by HPV DNA testing is an effective method for reducing cervical cancer and has proven more sensitive than cytology. To advance this approach, many molecular methods have been developed. Hybrid capture 2 provides semi-quantitative results in ratios of relative light units and positive cutoff values (RLU/PC). Twenty-five thousand and five patients were included in this study to analyze the correlation between the ratio of RLU/PC and stage of cervical dysplasia. The results show that the RLU/PC ratios ranged from 0-3500 while almost normal cases, ASC-US and ASC-H, had values below 200. Of those samples negative for cytology markers, 94.6% were normal and their RLU/PC ratios were less than 4. With an RLU/PC ratio greater than 4 and less than or equal to 300, the percentages in all age groups were normal 53.6%, LSIL 20.2%, ASC-US 17.2%, HSIL 6.13%, ASC-H 2.72%, and AGC 0.11%, respectively. In contrast, 64.0% of samples with a RLU/PC ratio greater than 300 and less than or equal to 3500 were LSIL. These results should contribute to cost effective cervical cancer management strategies. Further studies of associations with particular HPV genotypes would be useful to predict the risk of progression to cancer.

• Korean Journal of Head & Neck Oncology
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• v.13 no.1
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• pp.74-80
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• 1997

We have experienced 5 cases of unusual well differentiated thyroid carcinoma with insular component during the past 5 years. 4 cases were presented with cervical masses but I case (patient 2.) was initiallty with lung and brain metastasis. The tumors from 4 cases showed invasive growths but that of 1 cases(patient 1.) showed intrathyroidal. Total thyroidectomy and cervical lymphnode dissection(CCND or RND) was performed in 4 cases but only RND was performed in spite of mediastinal metastasis of the tumor in patient 5 under the patient's choice. During the follow-up period, we also performed radical nephrectomy and metastatectomy for the kidney and iliac bone metastasis respectively, in patint 2. Microcsopically, the tumors showed the insular growth patterns, focally(less than 50%) in 3 cases and predominantly(more than 75%) in 2 cases. And the insular componentas were combined with papillary carcinoma in 2 cases and follicular carcinoma in 3 cases. Cervical lymphnode metastases were confirmed in 4 cases. Patient 2 died of disease with metastases to lung, brain, bone and kidney, 52 months after initial therapy. Patient 1, 3 and 4 are alive and have no recurrence and distant metastasis. Patient 5 is also alive with the mediastinal metastasis. In our experience, the well differentiated thyroid carcinomas with insular component showed characteristic histologic features, aggressive behavior in initial presentation and unfavorable prognosis regardless of the percentage of the insular component.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.35 no.4
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• pp.227-235
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• 2013

Purpose: High risk human papillomavirus (HPV) is the main source of cervical cancer, nearly up to 100%. Because there are no affordable data regarding the incidence of HPV in different sites of oral cavity, the purpose of this study is to review the previous article and to find out about the incidence and types of HPV in specific areas of oral cavity. Methods: We examined a total of 106 patients with oral cavity cancer for HPV detection. Available DNA chip (MY-HPV chip kit$^{(R)}$, Mygene Co., Korea) was used for the detection of low risk HPV types (6, 11, 34, 40, 42, 43, 44) and high risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 54, 56, 58). Patients were previously diagnosed as invasive cancer of oral cavity. Specimen used for HPV detection was extracted from the main mass during resection and were tested for HPV type, performed by a DNA chip method. Results: Histologic results showed that there were squamous cell carcinomas, mucoepidermoid carcinomas, cystadenocarcinomas, leiomyosarcoma and etc. Among HPV positive cancer, 2 patients showed positive for high risk HPV type 16, 3 patients showed positive for low risk HPV type 6 and the other 2 patients were positive for other types of HPV. Of the 7 patients with HPV positive, 4 patients were on the tongue, 3 on the lower gingiva. Conclusion: Most of the HPV positive cancers were on the tongue in our study. Cervical cancer of HPV infection is reported to be increasing in our society and because HPV infection largely spreads by sexual contact, the incidence of oral cancer with HPV infection is greatly assumed to be on the increase, simultaneously. Because the incidence of HPV on specific areas of oral cavity among oral cancer patients is not identified, more studies are ongoing.

• The Korean Journal of Cytopathology
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• v.12 no.1
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• pp.1-15
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• 2001

The Bethesda System (TBS) was first developed in 1988 for the need to enhance the communication of the cytopathologic findings to the referring physician in unambiguous diagnostic terms. The terminology used in this reporting system should reflect current understanding of the pathogenesis of cervical/vaginal disease so the framework of the reporting system should be flexible enough to accommodate advances in medicine including virology, molecular biology, and pathology. Three years after the Introduction of TBS, the second Bethesda workshop was held to set or amend diagnostic criteria for each categories of TBS. TBS 1991 is now widely used. The third Bethesda workshop, The Bethesda System 2001 Workshop, was held in National Cancer institute Bethesda, Maryland from April 30 to May 2, 2001. Again, the goals of this workshop were to promote effective communication and to clarify in reporting cervical cytopathology results to clinicians and to provide with the information to make appropriate decisions about diagnosis and treatment. Nine forum groups were made and there were Web-based bulletin board discussions between October, 2000 and the first week of April, 2001. On the basis of bulletin board comments and discussions, the forum moderators recommended revised terminologies in the Workshop. Hot discussions were followed after the presentation by forum moderators during the workshop. Terminologies confusing clinicians and providing no additional informations regarding patient management were deleted in the workshop to clarify the cervicovaginal cytology results. Any informations related to the patient management were encouraged to add. So 'Satisfactory for evaluation but limited by...' of 'Specimen Adequacy' catergory was deleted. Terminology of 'Unsatisfactory' was further specified as 'Specimen rejected' and 'Specimen processed and examined, but unsatisfactory'. Terminologies of 'Benign Cellular Change' and 'Within Normal Limits' were combined and terminology was changed to 'Negative for intraepithelial lesion or malignancy'. In General categorization, category 'Other' was newly inserted and the presence of 'Endometrial cells' in women over 40 years old can be checked. Although the category 'Benign Cellular Change' was deleted, the organisms or reactive changes of this category can be listed in the descriptive diagnoses. Terminologies of ASCUS and AGUS were changed to atypical squamous cell and atypical glandular cell, respectively. Diagnostic term of 'Adenocarcinoma in situ', which is highly reproducible with reliable diagnostic criteria, was newly Inserted. The category of hormonal evaluation was deleted. Criteria for liquid-based specimen were discussed. Reporting by computer-assisted cytology was discussed and terminology for automated review was newly inserted. This is not the final edition of Bethesda 2001. The final document can be prepared before the ASCCP meeting in which Consensus Guidelines for the Management on Cytology Abnormalities and Cervical Precursors will develop in September 2001.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1151-1158
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• 2012

High-risk human papillomavirus (HPV) genotypes are the major cause of cervical cancer. Hence, HPV genotype detection is a helpful preventive measure to combat cervical cancer. Recently, several HPV detection methods have been developed, each with different sensitivities and specificities. The objective of this study was to compare HPV high risk genotype detection by an electrochemical DNA chip system, a line probe assay (INNO-LiPA) and sequencing of the L1, E1 regions. A total of 361 cervical smears with different cytological findings were subjected to polymerase chain reaction-sequencing and electrochemical DNA chip assessment. Multiple infections were found in 21.9% (79/361) of the specimens, most prevalently in 20-29-year olds while the highest prevalence of HPV infection was found in the 30-39-year age group. The most prevalent genotype was HPV 16 at 28.2% (138/489) followed by HPV 52 at 9.6% (47/489), with the other types occurring at less than 9.0%. The electrochemical DNA chip results were compared with INNO-LiPA and sequencing (E1 and L1 regions) based on random selection of 273 specimens. The results obtained by the three methods were in agreement except for three cases. Direct sequencing detected only one predominant genotype including low risk HPV genotypes. INNO-LiPA identified multiple infections with various specific genotypes including some unclassified-risk genotypes. The electrochemical DNA chip was highly accurate, suitable for detection of single and multiple infections, allowed rapid detection, was less time-consuming and was easier to perform when compared with the other methods. It is concluded that for clinical and epidemiological studies, all genotyping methods are perfectly suitable and provide comparable results.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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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.

• IMMUNE NETWORK
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• v.3 no.1
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• pp.16-22
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• 2003

Background: The S100A2 gene, also known as S100L or CaN19, encodes a protein comprised of 99-amino acids, is a member of the calcium-binding proteins of EF-hand family. According to a recent study, this gene was over-expressed in several early and malignant carcinomas compared to normal tissues. To elucidate the role of S100A2 protein in the process during carcinogenesis, production of monoclonal antibody specific to the protein is essential. Methods: First, cDNA sequence coding for ORF region of human S100A2 gene was amplified and cloned into an expression vector to produce GST fusion protein. Recombinant S100A2 protein and subsequently, monoclonal antibody to the protein were produced. The specificity of anti-S100A2 monoclonal antibody was confirmed by immunoblot analysis of cross reactivity to other recombinant proteins of S100A family (GST-S100A1, GST-S100A4 and GST-S100A6). To confirm the relation of S100A2 to cervical carcinogenesis, S100A2 protein in early cervical carcinoma tissue was immunostained using the monoclonal antibody. Results: GST-S100A2 recombinant protein was purified by affinity chromatography and then fusion protein was cleaved and S100A2 protein was isolated. The monoclonal antibody (KK0723; Korean patent pending #2001-30294) to the protein was produced and the antibody did not react with other members of EF-hand family proteins such as S100A1, S100A4 and S100A6. Conclusion: These data suggest that anti-S100A2 monoclonal antibody produced in this study can be very useful for the early detection of cervical carcinoma and elucidation of mechanism during the early cervical carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.559-564
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• 2015

Background: The participation of women in cervical cancer screening in Malaysia is low. Self-sampling might be able to overcome this problem. The aim of this study was to assess the reliability of self-sampling for cervical smear in our country. Materials and Methods: This cross-sectional study was conducted on 258 community dwelling women from urban and rural settings who participated in health campaigns. In order to reduce the sampling bias, half of the study population performed the self-sampling prior to the physician sampling while the other half performed the self-sampling after the physician sampling, randomly. Acquired samples were assessed for cytological changes as well as HPV DNA detection. Results: The mean age of the subjects was $40.4{\pm}11.3years$. The prevalence of abnormal cervical changes was 2.7%. High risk and low risk HPV genotypes were found in 4.0% and 2.7% of the subjects, respectively. A substantial agreement was observed between self-sampling and the physician obtained sampling in cytological diagnosis (k=0.62, 95%CI=0.50, 0.74), micro-organism detection (k=0.77, 95%CI=0.66, 0.88) and detection of hormonal status (k=0.75, 95%CI=0.65, 0.85) as well as detection of high risk (k=0.77, 95%CI=0.4, 0.98) and low risk (K=0.77, 95%CI=0.50, 0.92) HPV. Menopausal state was found to be related with 8.39 times more adequate cell specimens for cytology but 0.13 times less adequate cell specimens for virological assessment. Conclusions: This study revealed that self-sampling has a good agreement with physician sampling in detecting HPV genotypes. Self-sampling can serve as a tool in HPV screening while it may be useful in detecting cytological abnormalities in Malaysia.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6693-6696
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• 2013

Background: Cold knife conization is a surgical procedure that allows both diagnosis and treatment of cervical lesions at the same time. It is mainly performed for indications of high-grade cervical intraepithelial neoplasia (CIN). In this study, we aimed to investigate the clinical outcome of cases without CIN in cold knife conization specimen, following a high-grade lesion (CIN2/3) in cervical biopsy. Materials and Methods: We performed a retrospective cohort study at a tertiary referral hospital between January $1^{st}$ 2008 and August $1^{st}$ 2012. Cases that underwent cold knife conization for CIN2/3 within the study period were included. Cone-negative (Group 1) and cone-positive (Group 2) cases were analyzed for various clinical parameters, and were compared in the 1-year post-conization period for histological recurrence and human papillomavirus (HPV) DNA status. Results: A total of 173 women underwent cold knife conization for CIN2/3 within the study period. Twenty-two cases (12.7%) were included in Group 1 and 151 cases (87.3%) in Group 2. There were no significant differences between the two groups in terms of age, gravidity, parity, menopausal status and HPV-DNA status (pre-conization and 1 year post-conization) (p>0.05). Recurrence rates were also similar between the groups (9.1% vs 9.9%, p>0.05). Conclusions: Clinical outcomes were similar in terms of histological recurrence and HPV persistence after 1 year of follow-up between cone-negative and cone-positive cases. Clinical follow-up of cone-negative cases should therefore be performed similar to cone-positive cases.

• The Korean Journal of Cytopathology
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• v.18 no.1
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• pp.1-12
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• 2007

Approximately 70% of cervical cancers are caused by HPV types 16/18 and thus the implementation of vaccination programmes with vaccines against HPV types 16/18 will have a major impact on the incidence of cervical cancer worldwide. However, this reduction will not be seen until several decades after full implementation of such vaccination programmes since the vaccines must be given to young adolescents before exposure to the virus and women who are already sexually active are not likely to be protected. Both GSK and Merck insist that even vaccinated women must continue to participate in regular cervical screening by the most sensitive method available since the vaccine can only give protection against up to 70% of cervical cancers. It is unlikely that the current vaccines will be modified to include additional high risk HPV types in the foreseeable future. While HPV testing is highly sensitive, it is not recommended for women under 30 years of age nor for vaccinated women. Additionally, HPV testing has poor specificity. The Digene Hybrid Capture 2 test is licensed for use only in conjunction with a cytology test, not as a stand-alone test, and the high risk panel has recognised cross reactivity with low risk HPV types. None of the other HPV test methods currently commercially available are FDA approved and all must be internally validated before use. This makes comparison of test results between laboratories difficult. The most sensitive and specific screening test currently available for women of all ages is the Cytyc ThinPrep System consisting of the ThinPrep Pap Test (TPPT) and the ThinPrep Imaging System (Imager). The TPPT was the first LBC system approved by the US FDA in 1996 and there are about 4,000 processors in use worldwide. The Imager was FDA approved in 2003 and over 350 systems are in routine use, mainly in the US. 40% of TPPT in the US are processed on Imager. There is clear evidence in peer reviewed literature that the Imager increases laboratory productivity by 100% and growing evidence that Imager detects more high grade SIL than the conventional smear or manual evaluation of TPPT. This aspect is particularly important since the number of cytological abnormalities will decrease as vaccination programmes are implemented. Cytotechnologists will see fewer and fewer abnormal smears and their skills will be put at risk. By doubling throughput, Imager will allow cytotechnologists to maintain their skills.