| 1. |
- Cui, Baoxia, et al.
(author)
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Mutation of PIK3CA : possible risk factor for cervical carcinogenesis in older women
- 2009
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In: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 34:2, s. 409-416
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Journal article (peer-reviewed)abstract
- PIK3CA encodes the p110alpha catalytic subunit of PI 3-kinase, which regulates signaling pathways important for neoplasia, cell proliferation and apoptosis. Somatic mutations in this gene have been detected in several solid human tumors. We investigated these mutations in cervical carcinoma and its precursors, and their association with HPV infection and patient clinical data. The mutations were analyzed using post-PCR direct genomic DNA sequencing. Samples included 9 cervical cancer cell lines, 184 invasive cervical carcinomas, and 30 cervical neoplasias. Missense mutations of PIK3CA were identified in 15/184 (8.15%) invasive cervical carcinomas. One novel mutation G1638C (Q546H) was found. Three mutations were identified in the cervical cancer lines. No mutations were found in the precursors. The difference in mutation frequency between invasive and pre-invasive lesions was not significant (p=0.1372). In relation to age and HPV, the mutation rate was significantly higher in patients>or=60 years (p=0.001), while the rate of HPV infection was higher in patients
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| 2. |
- Eklund, Carina, et al.
(author)
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Continuing global improvement in human papillomavirus DNA genotyping services : The 2013 and 2014 HPV LabNet international proficiency studies
- 2018
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In: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 101, s. 74-85
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Journal article (peer-reviewed)abstract
- Background: Accurate and internationally comparable human papillomavirus (HPV) DNA detection and typing services are essential for HPV vaccine research and surveillance. Objectives: This study assessed the proficiency of different HPV typing services offered routinely in laboratories worldwide. Study design: The HPV Laboratory Network (LabNet) has designed international proficiency panels that can be regularly issued. The HPV genotyping proficiency panels of 2013 and 2014 contained 43 and 41 coded samples, respectively, composed of purified plasmids of sixteen HPV types (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68a and 68b) and 3 extraction controls. Proficient typing was defined as detection in both single and multiple infections of 50 International Units of HPV 16 and HPV 18 and 500 genome equivalents for the other 14 HPV types, with at least 97% specificity. Results: Ninety-six laboratories submitted 136 datasets in 2013 and 121 laboratories submitted 148 datasets in 2014. Thirty-four different HPV genotyping assays were used, notably Linear Array, HPV Direct Flow-chip, GenoFlow HPV array, Anyplex HPV 28, Inno-LiPa, and PGMY-CHUV assays. A trend towards increased sensitivity and specificity was observed. In 2013, 59 data sets (44%) were 100% proficient compared to 86 data sets (59%) in 2014. This is a definite improvement compared to the first proficiency panel, issued in 2008, when only 19 data sets (26%) were fully proficient. Conclusion: The regularly issued global proficiency program has documented an ongoing worldwide improvement in comparability and reliability of HPV genotyping services.
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| 3. |
- Eklund, Carina, et al.
(author)
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Global Improvement in Genotyping of Human Papillomavirus DNA: the 2011 HPV LabNet International Proficiency Study.
- 2014
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In: Journal of Clinical Microbiology. - 1098-660X. ; 52:2, s. 449-459
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Journal article (peer-reviewed)abstract
- Accurate and internationally comparable human papillomavirus (HPV) DNA genotyping is essential for HPV vaccine research and for HPV surveillance. The HPV Laboratory Network (LabNet) has designed international proficiency studies that can be issued regularly and in a reproducible manner. The 2011 HPV genotyping proficiency panel contained 43 coded samples composed of purified plasmids of 16 HPV types (HPV6, -11, -16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -68a, and -68b) and 3 extraction controls. Tests that detected 50 IU of HPV16 and HPV18 and 500 genome equivalents for the other 14 HPV types in both single and multiple infections were considered proficient. Ninety-six laboratories worldwide submitted 134 data sets. Twenty-five different HPV genotyping assay methods were used, including the Linear Array, line blot/INNO-LiPA, PapilloCheck, and PCR Luminex assays. The major oncogenic HPV types, HPV16 and HPV18, were proficiently detected in 97.0% (113/116) and 87.0% (103/118) of the data sets, respectively. In 2011, 51 data sets (39%) were 100% proficient for the detection of at least one HPV type, and 37 data sets (28%) were proficient for all 16 HPV types; this was an improvement over the panel results from the 2008 and 2010 studies, when <25 data sets (23% and 19% for 2008 and 2010, respectively) were fully proficient. The improvement was also evident for the 54 laboratories that had also participated in the previous proficiency studies. In conclusion, a continuing global proficiency program has documented worldwide improvement in the comparability and reliability of HPV genotyping assay performances.
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| 4. |
- Eklund, Carina, et al.
(author)
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The 2010 global proficiency study of Human Papillomavirus genotyping in vaccinology.
- 2012
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In: Journal of Clinical Microbiology. - 1098-660X. ; 50:7, s. 2289-2298
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Journal article (peer-reviewed)abstract
- Accurate and internationally comparable Human Papillomavirus (HPV) DNA genotyping is essential both for evaluation of HPV vaccines and for effective monitoring and implementation of vaccination programs. World Health Organisation (WHO) HPV Laboratory Network (LabNet) regularly issues international proficiency studies. The 2010 HPV genotyping proficiency panel for HPV vaccinology contained 43 coded samples composed of purified plasmids of sixteen HPV types (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68a and 68b) and 3 coded extraction controls. Proficient typing was defined as detection in both single and multiple infections of 50 International Units (IU) of HPV 16 and HPV 18 DNA and 500 genome equivalents (GE) for the other 14 HPV types. Ninety-eight laboratories worldwide submitted a total of 132 datasets. Twenty-four different HPV genotyping assay methods were used, with Linear Array being most commonly used. Other major assays used were Lineblot/Inno-LiPa, CLART, type-specific real-time PCR, PCR-Luminex and different microarray assays. Altogether 72 data sets were proficient for detection of more than one type, only 26 data sets proficiently detected all sixteen HPV types. The major oncogenic HPV types, 16 and 18, were proficiently detected in 95.0% (114/120) and 87.0% (94/108) of datasets, respectively. Forty-six datasets reported multiple false positive results and were considered non-proficient. A trend towards increased sensitivity of assays was seen for the 41 laboratories that participated in both 2008 and 2010. In conclusion, continued global proficiency studies will be required for establishing comparable and reliable HPV genotyping services for vaccinology worldwide.
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| 5. |
- Gharizadeh, Baback, et al.
(author)
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Sentinel-base DNA genotyping using multiple sequencing primers for high-risk human papillomaviruses
- 2006
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In: Mol Cell Probes. - : Elsevier BV. ; 20:3-4, s. 230-238
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Journal article (peer-reviewed)abstract
- Despite the various technologies in place for genotyping human papillomaviruses (HPV), clinical use and clinical research demand a method that is fast, more reliable and cost-effective. The technology described here represents a breakthrough development in that direction. By combining the method of multiple sequencing primers with DNA sequencing, we have developed a rapid assay for genotyping HPV that relies on the identification of a single, type-specific 'sentinel' base. As described here, the prototype assay has been developed to recognize the 12 most high-risk HPV types (HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) and is capable of recognizing and simultaneously genotyping multiple HPV co-infections. By providing sequence information on multiple HPV infections, this method eliminates the need for labor- and cost-intensive PCR cloning. These proof-of-concept studies establish the assay to be accurate, reliable, rapid, flexible, and cost-effective, providing evidence of the feasibility this technique for use in clinical settings.
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| 6. |
- Nastic, Denis, et al.
(author)
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A Selective Biomarker Panel Increases the Reproducibility and the Accuracy in Endometrial Biopsy Diagnosis
- 2017
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In: International Journal of Gynecological Pathology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0277-1691 .- 1538-7151. ; 36:4, s. 339-347
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Journal article (peer-reviewed)abstract
- Grading and histologic typing of endometrial cancer in biopsy material has a direct impact on the decision to perform lymphadenectomy and/or omentectomy in many cancer centers. Endometrial biopsies are among the most common general surgical pathology specimens. Multiple studies have shown that biopsy diagnosis suffers from a lack of reproducibility. Although many biomarkers have been proposed, none have been demonstrated to improve the diagnosis in the biopsy setting. In this study, 70 biopsies with endometrial carcinoma were supplemented with a biomarker panel consisting of ER, PR, P53, and DNA ploidy. A representative H&E slide was scanned digitally and made available to 12 gynecologic pathologists in 4 Nordic countries: Finland, Denmark, Sweden, and Norway. Reviewers diagnosed the cases both before and after being provided with the biomarker results. The interobserver percent agreement and Cohen κ improved from 75.8% (κ=0.52, moderate) to 84% (κ=0.68, substantial) with inclusion of the biomarker panel. Agreement with the subsequent hysterectomy diagnosis also improved from 83.6% (κ=0.67) to 88.7% (κ=0.77). There was no statistical improvement between a reflex (84% agreement) and a reflective testing algorithm (82.9% agreement), suggesting that the selective use of biomarkers is appropriate. Difficult cases were almost exclusively high-grade tumors. Finally, a statistical model indicated that only P53 and DNA ploidy, in conjunction with an H&E review, had an impact on the decision to upgrade or downgrade cases.
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| 7. |
- Reuschenbach, Miriam, et al.
(author)
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Characterization of humoral immune responses against p16, p53, HPV16 E6 and HPV16 E7 in patients with HPV-associated cancers
- 2008
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 123:11, s. 2626-2631
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Journal article (peer-reviewed)abstract
- The cellular tumor suppressor p16 is strongly overexpressed in cervical cancers and precancers. We have previously demonstrated that infiltrating T lymphocytes reactive against p16 can be found in cervical cancer patients. Here, we analyzed whether 16 induces humoral immune responses. Sera of patients with cervical cancer, oropharyngeal cancer, colorectal cancer and autoimmune disease were included. A total of 919 sera were analyzed. including 486 matched sera from a cervical cancer case control study. p16 antibodies were analyzed in western blot and a newly developed peptide ELISA covering the complete p16 protein. In addition, a Luminex-based multiplex assay was used for simultaneous detection of antibodies directed against p16, p53, HPV16 E6 and HPV16 E7. In all entities, only low p16 antibody reactivity was observed. Epitope mapping revealed 2 predominant epitope regions of the p16 protein. No significant difference in p16 antibody frequency (OR = 0.9; 95% Cl = 0.6-1.3) and p-53 antibody frequency (OR = 0.6; 95% Cl = 0.3-1.2) was found between patients and healthy controls in the cervical cancer case control study. Antibodies against the HPV16 oncoproteins E6 and E7 were detected more frequently in cervical cancer patients when compared with healthy controls (E6 OR = 27.8; 95 % Cl = 11. - 69.7, E7 OR = 5.7; 95% Cl = 2.9-11.1). In conclusion. despite the strong expression of p16 and the observed induction of cellular immune responses, antibody reactivity against p16 was observed only at very low levels independent of the disease background. (C) 2008 Wiley-Liss, Inc.
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| 8. |
- Strander, Björn, 1952, et al.
(author)
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Does HPV-status 6-12 months after treatment of high grade dysplasia in the uterine cervix predict long term recurrence?
- 2007
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In: Eur J Cancer. ; 43:12, s. 1849-55
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Journal article (peer-reviewed)abstract
- BACKGROUND: Women once treated for high grade cervical dysplasia have a high long term risk for developing new dysplasia or cancer. OBJECTIVES: To investigate if human papilloma virus (HPV)-negativity after treatment of cervical dysplasia reduces the need for frequent long term follow up. DESIGN: Case/control study based on archival smears. METHODS: Women with cervical intraepithelial neoplasi (CIN)2-3, treated for dysplasia and with recurrence of CIN2+ more than 2 years after treatment were compared with controls without recurrence, matched for age and date of treatment. High risk-HPV-DNA were analysed with PCR from two archival smears per woman. Mean follow up time was 14.6 years. RESULTS: 24% (45/189) of cases and 11% (43/378) of controls were HPV-positive in any of two smears. Odds ratio (OR)=2.5 (1.6-3.8). CONCLUSION: HPV-status 6-12 months after treatment of high grade dysplasia is of limited value for the design of long term follow up.
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| 9. |
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| 10. |
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| 11. |
- Zheng, Biying, et al.
(author)
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Genetic polymorphism of chemokine receptors CCR2 and CCR5 in Swedish cervical cancer patients
- 2006
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In: Anticancer research. - 1791-7530. ; 26:5B, s. 3669-3674
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Journal article (peer-reviewed)abstract
- Chemokines are chemotactic cytokines that orchestrate leukocyte trafficking in tissues, thus, playing an important role in regulation of immunological processes. The aim of this study was to investigate the association of human papillomavirus (HPV) infection and cervical cancer with two DNA polymorphisms of the chemokine receptors CCR5-Delta 32 and CCR2-64L The study material consisted of 50 cervical intraepithelial neoplasia (CIN) cases and 50 of age and sampling-date matched controls, 100 invasive cervix cancer cases and 100 of their corresponding matched disease-free controls. Pyrosequencing (TM) was employed to genotype the CCR2-64I polymorphism. CCR5-Delta 32 was genotyped using standard PCR fragment length analysis. The frequencies of CCR2 and CCR5 genotypes from 150 patients and 150 healthy controls were representative of the general population according to the Hardy-Weinberg equilibrium analysis. Risk association was computed with conditional logistic regression analysis. HPV-positive individuals with the rare CCR5 Delta 32/Delta 32 genotype have a risk of 4.58 (CI=0.40-52.64, p-valite=0.045) compare to HPV negative group. The Delta-32 mutation on the CCR locus is imperceptibly associated with increased risk of HPV infection. In total, cervical neoplasia was not associated with genetic polymorphism of CCR2 and CCR5.
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| 12. |
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