scholarly journals Identification of Candidate Protein Biomarkers for CIN2+ Lesions from Self-Sampled, Dried Cervico–Vaginal Fluid Using LC-MS/MS

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2592
Author(s):  
Ariadna Lara Gutiérrez ◽  
Julia Hedlund Lindberg ◽  
Ganna Shevchenko ◽  
Inger Gustavsson ◽  
Jonas Bergquist ◽  
...  

Molecular screening programs for cervical cancer detect the presence of human papilloma virus (HPV) in cell material or vaginal fluids. Persistent infection with high-risk HPV is a necessary pre-requisite, but the majority of infections do not lead to pathological states. Additional biomarkers are needed to increase the specificity of the molecular tests. Here, we have investigated the possibility of detecting protein biomarkers using mass spectrometry from dried self-sampled cervico–vaginal fluid deposited on FTA cards. We found significant intra-individual correlations (p < 2.2 × 10−16), although heterogenous protein profiles were obtained between individuals. Out of 3699 proteins found in total, 169 were detected in at least 95% of the samples. Using a discovery/replication design, 18 proteins were found to be significant in the discovery cohort, with higher values in those cases compared to controls. All of these were found to also have higher levels among the cases in the replication cohort, with one protein (DEAD-Box Helicase) remaining statistically significant. Finally, a predictive 7-protein multivariate model was developed with a sensitivity and specificity of 0.90 and 0.55, respectively. Our results demonstrate that robust measurements of protein biomarkers can be obtained from self-sampled dried CVF and that these could be used to predict cervical cancer pre-stages.

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Charlotte A. Brown ◽  
Johnannes Bogers ◽  
Shaira Sahebali ◽  
Christophe E. Depuydt ◽  
Frans De Prins ◽  
...  

Since the Pap test was introduced in the 1940s, there has been an approximately 70% reduction in the incidence of squamous cell cervical cancers in many developed countries by the application of organized and opportunistic screening programs. The efficacy of the Pap test, however, is hampered by high interobserver variability and high false-negative and false-positive rates. The use of biomarkers has demonstrated the ability to overcome these issues, leading to improved positive predictive value of cervical screening results. In addition, the introduction of HPV primary screening programs will necessitate the use of a follow-up test with high specificity to triage the high number of HPV-positive tests. This paper will focus on protein biomarkers currently available for use in cervical cancer screening, which appear to improve the detection of women at greatest risk for developing cervical cancer, including Ki-67,p16INK4a, BD ProEx C, and Cytoactiv HPV L1.


2005 ◽  
Vol 16 (2) ◽  
pp. 83-91 ◽  
Author(s):  
François Coutlee ◽  
Danielle Rouleau ◽  
Alex Ferenczy ◽  
Eduardo Franco

Human papillomaviruses (HPVs) are the etiological agents of several genital cancers, including cancer of the uterine cervix. The detection of HPV infection in genital samples may increase the sensitivity of primary and secondary screenings of cervical cancer. HPV testing may also improve the specificity of screening programs, resulting in the avoidance of overtreatment and cost savings for confirmatory procedures. The major determinants of clinical progression of HPV infection include persistence of HPV infection, involvement of high-risk HPV types, high HPV viral load, integration of viral DNA and presence of several potential cofactors. Signal amplification HPV-DNA detection techniques (Hybrid Capture II, Digene Corporation, USA) are standardized, commercially available, and capable of detecting several high-risk HPV types. They also increase the sensitivity of screening for high-grade lesions in combination with cytology. The sensitivity of these techniques to detect high-grade lesions is higher than that of cytology, but the referral rate for colposcopy is greater. These techniques are approved for the triage to colposcopy of women with cervical smears interpreted as atypical squamous cells of undetermined significance. Triage and screening for cervical cancer using HPV will probably be restricted to women aged 30 years or older because of the high prevalence of infection in younger women. Amplification techniques are ideal for epidemiological studies because they minimize the misclassification of HPV infection status. These techniques can detect low HPV burden infections. Consensus primers amplify most genital types in one reaction, and the reverse hybridization of amplicons with type-specific probes allows for the typing of HPV-positive samples. Consensus PCR assays are currently under evaluation for diagnostic purposes. HPV testing is currently implemented for the clinical management of women.


2016 ◽  
Vol 29 (2) ◽  
pp. 291-319 ◽  
Author(s):  
Eileen M. Burd

SUMMARYHigh-risk human papillomaviruses (HPVs) cause essentially all cervical cancers, most anal and oropharyngeal cancers, and some vaginal, vulvar, and penile cancers. Improved understanding of the pathogenesis of infection and the availability of newer tests are changing the approach to screening and diagnosis. Molecular tests to detect DNA from the most common high-risk HPVs are FDA approved for use in conjunction with cytology in cervical cancer screening programs. More-specific tests that detect RNA from high-risk HPV types are now also available. The use of molecular tests as the primary screening tests is being adopted in some areas. Genotyping to identify HPV16 and -18 has a recommended role in triaging patients for colposcopy who are high-risk HPV positive but have normal cytology. There are currently no recommended screening methods for anal, vulvar, vaginal, penile, or oropharyngeal HPV infections. HPV testing has limited utility in patients at high risk for anal cancer, but p16 immunohistochemistry is recommended to clarify lesions in tissue biopsy specimens that show moderate dysplasia or precancer mimics. HPV testing is recommended for oropharyngeal squamous cell tumors as a prognostic indicator. Ongoing research will help to improve the content of future guidelines for screening and diagnostic testing.


2012 ◽  
Vol 22 (6) ◽  
pp. 1063-1068 ◽  
Author(s):  
Teeraporn Chinchai ◽  
Jira Chansaenroj ◽  
Sukumarn Swangvaree ◽  
Pairoj Junyangdikul ◽  
Yong Poovorawan

Background and ObjectiveCervical cancer is the second most common female genital cancer worldwide. There is strong epidemiological and molecular evidence indicating that human papillomavirus (HPV) infection is a necessary event in the development of cervical intraepithelial lesion and subsequent invasive carcinoma. The aim of this study was to investigate the HPV genotype distribution and prevalence in cervical cancer of Thai women.Materials and MethodsOne hundred fifty-five cervical cancer specimens were enrolled in this study. The HPV genotypes were determined by means of the combined use of a line probe assay (INNO-LiPA) and DNA chip methods.ResultsOf the overall prevalence of HPV in the study group, 83.2% and 11.6% of the cases had single and multiple genotype infections, respectively. The most prevalent genotypes were HPV 16 (51%), followed by HPV 18 (20%), HPV 52 (10.3%), HPV 58 (5.8%), and HPV 33 (4.5%). All HPV genotypes found in this study could be classified as 13 high-risk HPV, 2 low-risk HPV, and 2 additional types. Of the specimens, 94.8% had at least one high-risk HPV genotype infection.ConclusionAs for the potential benefits of commercially available prophylactic vaccines to prevent HPV infection in Thailand, both vaccines (bivalent and quadrivalent) can protect from HPV-related cervical cancer in only approximately 71%. Therefore, screening programs such as routine Papanicolaou test, cytology, and HPV DNA detection are still essential for cervical cancer prevention. Moreover, future generations of HPV vaccines should also include the other most common genotypes and decrease the severe adverse effects reported at the present time.


2016 ◽  
Vol 2 (3_suppl) ◽  
pp. 40s-40s
Author(s):  
Sally N. Adebamowo ◽  
Eileen O. Dareng ◽  
Ayotunde O. Famooto ◽  
Rasheed A. Bakare ◽  
Clement A. Adebamowo ◽  
...  

Abstract 65 Background: Cervical cancer is the second most common cancer in Africa. Much remains unknown about the prevalence and pathogenicity of human papillomavirus (HPV) types and the mechanism of disease, and there is a need for new biomarkers for screening programs. Methods: ACCME is a multicenter prospective cohort study of host germline, somatic and HPV genomics and epigenomics, and vaginal microenvironment; and their association with cervical cancer in 10,000 HIV negative women in Nigeria. Data on demographic, lifestyle, medical history, serum, germline DNA, HPV genotype, and vaginal pH are collected at baseline and during follow up visits every 6 months. Samples of exfoliated cervical cells are analyzed for high risk HPV with Roche LINEAR ARRAY and vaginal bacterial composition and abundance are characterized by deep sequencing of barcoded 16S rRNA gene fragments (V4) on a Illumina MiSeq platform. Colposcopies and biopsies are conducted on participants with clinical lesions and those with persistent high risk HPV infections. Results: By December 2015, 10,000 participants had been enrolled in the ACCME cohort. The mean (SD) age of the study participants at baseline was 40 (10) years. Most of the participants were married (76%), attended university (44%), and had professional jobs (37%). All the study participants have had vaginal sex, 17% have had oral sex, and only 2% have ever had anal sex. We found 30% of the study participants were HPV positive and 70% were HPV negative. The mean (SD) vaginal pH in the study population was 5.2 (0.5). Further analyses to characterize high-risk HPV types and determine persistence will be conducted at each follow up visit. Also, characterization of cervical cytokines and vaginal microbiome will be conducted after the follow up visits for all participants have been conducted. Conclusions: ACCME is a paradigm for translational research in biomarker discovery that addresses high impact public health challenges affecting women's health in Africa and the rest of the world. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: No COIs from the authors.


2018 ◽  
Vol 1 (1) ◽  
pp. 32-36
Author(s):  
Eleazar Ndabarora ◽  
Dariya Mukamusoni ◽  
Clarte Ndikumasabo ◽  
Védaste Ngirinshuti

Cervical cancer is one of the leading causes of morbidity and mortality globally and in Sub-Saharan Africa in particular. There is evidence that early detection and early management of cases are the best strategies to prevent and control this health threat, since treatment of the later stages of the diseases are very expensive. The objectives of the review were: (1) to identify and review studies on the prevalence of cervical cancer and determinants of early detection in Sub-Saharan Africa, and (2) to recommend further studies and interventions based on the findings of this review. Extensive literature search was conducted using the MeSH terms. Articles on cervical cancer and/or determinants of early detection which fulfilled inclusion criteria were reviewed independently by three reviewers. The prevalence of cervical cancer in Sub-Saharan Africa is increasing. Although there are evidences that cervical cancer screening programs are practical and feasible even in resource-limited settings in Sub-Saharan Africa, there is a very low uptake of cervical cancer screening and there are key factors that need to be addressed in order to make these programs established and effective.


Author(s):  
Marina Kochiyeva

Data on modern methodological approaches that are used in screening for cancer are summarized. General principles of organizing screening studies are examined from the perspective of evidence-based medicine, target population, research methods, and effectiveness of the implemented screening programs for breast cancer, cervical cancer, and colon cancer are determined.


2017 ◽  
pp. 99-103
Author(s):  
Van Bao Thang Phan ◽  
Hoang Bach Nguyen ◽  
Van Thanh Nguyen ◽  
Thi Nhu Hoa Tran ◽  
Viet Quynh Tram Ngo

Introduction: Infection with HPV is the main cause of cervical cancer. Determining HPV infection and the types of HPV plays an important role in diagnosis, treatment and prognosis of cervicitis/cervical cancer. Aims: Determining proportion of high-risk HPV types and the occurrence of coinfection with multiple HPV types. Methods: 177 women with cervicitis or abnormal Pap smear result were enrolled in the study. Performing the real-time PCR for detecting HPV and the reverse DOT-BLOT assay for determining type of HPV in cases of positive PCR. Results: 7 types of high-risk HPV was dectected, the majority of these types were HPV type 18 (74.6%) and HPV type 16 (37.6%); the proportion of infection with only one type of HPV was 30.4% and coinfection with multiple HPV types was higher (69.6%), the coinfected cases with 2 and 3 types were dominated (32.2% and 20.3%, respectively) and the coinfected cases with 4 and 5 types were rare. Conclusion: Use of the real-time PCR and reverse DOT-BLOT assay can determine the high-risk HPV types and the occurrence of coinfection with multiple HPV types. Key words: HPV type, Reverse DOT-BLOT, real-time PCR,PCR, cervical cancer


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