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Cervical Cancer & Cervical Dysplasia: Screening, Diagnosis, and Treatment

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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 13025

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Special Issue Editor

Dr. Jeong-Yeol Park

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Guest Editor

Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea
Interests: cervical cancer; endometrial cancer; ovarian cancer; cancer surgery; chemotherapy; cancer imaging; molecular diagnostics; optical diagnostics

Special Issue Information

Dear Colleagues,

Despite the introduction of screening programs and preventive vaccines, cervical cancer remains an significant health problem for women worldwide, with a high incidence and mortality rate among female cancers. Therefore, an improved screening program for cervical cancer diagnosis and studies proving the effectiveness of the cervical cancer preventive vaccine are needed. Since cervical cancer most often occurs through cervical dysplasia, the preliminary stage of cervical cancer, effective diagnostic and treatment methods for cervical dysplasia should be developed. Furthermore, to reduce mortality from cervical cancer, further studies on more efficacious treatments for advanced, metastatic and recurrent cervical cancer must continue. This upcoming Special Issue focuses on the diagnosis and treatment of cervical cancer and cervical dysplasia. Topics of interest include, but are not limited to:

Diagnosis of cervical dysplasia and cervical cancer;
Treatment of cervical dysplasia and cervical cancer;
Cervical cancer screening;
Efficacy of preventive and therpeutic vaccines for cervical dysplasia and cervical cancer;
Diagnosis, treatment and prognosis of cervical adenocarcinoma;
Predictive and prognostic biomarkers of cervical cancer;
Immunotherapy and other targeted therapies of cervical cancer;
Fluorescent-imaging-guided surgery for cervical cancer (i.e. sentinel lymph node mapping);
Radiologic and pathologic diagnosis of cervical cancer;
Radiation therapy for cervical cancer;
Minimally invasive surgery for cervical cancer.

Dr. Jeong-Yeol Park
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

cervical dysplasia
cervical cancer
diagnosis
management
vaccine
immunotherapy
radiation therapy
surgery
screening
biomarker

Published Papers (7 papers)

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Research

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14 pages, 837 KiB

Open AccessArticle

Understanding the Dynamics of Human Papillomavirus and Diagnostic Discrepancies in Cervical Pathology: A Single Center Experience

by Milena Zamurovic, Ana Tomic, Aleksandra Pikula, Sara Simanic, Aleksandra Knezevic, Marko Jankovic, Milan Lackovic, Elena Djakovic and Marija Rovcanin

Diagnostics 2023, 13(24), 3614; https://doi.org/10.3390/diagnostics13243614 - 7 Dec 2023

Viewed by 927

Abstract

Cervical cancer (CC) is the most prevalent gynecological malignancy and a leading cause of death among women. It is primarily caused by human papillomavirus (HPV) infection, with 99.7% of cases showing high-risk HPV genotypes. This study sheds light on HPV dynamics as well as the discrepancies of different CC screening modalities results while highlighting factors that may have contributed to such a scenario. Moreover, we underscore the importance of the non-viral etiology of CC as well. We examined the current trends of HPV infection and its effects on cervical health in women treated at a tertiary care center in Belgrade, Serbia. Patients with abnormal colposcopy findings like dysplasia and re-epithelization were more likely to test negative for HPV (p < 0.001). Interestingly, women with a positive Pap smear tested HPV negative significantly more often (p = 0.041). Finally, HPV-positive individuals were more likely to have CIN I and II histologies (p < 0.001), while CIN III occurred equally in women with and without the virus. It may be inferred that inconsistencies in detecting HPV and the presence of cervical lesions may eventually result in adjustments to screening guidelines, as is crucial to adopt a meticulous approach to promote periodical CC screening, as initial samples may test negative for HPV. Full article

(This article belongs to the Special Issue Cervical Cancer & Cervical Dysplasia: Screening, Diagnosis, and Treatment)

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15 pages, 813 KiB

Open AccessArticle

Comparing the Costs and Diagnostic Outcomes of Replacing Cytology with the QIAsure DNA Methylation Test as a Triage within HPV Primary Cervical Cancer Screening in The Netherlands

by Krishnan Puri Sudhir, Eva Kagenaar, Michelle Meijer, Albertus T. Hesselink, Elisabeth Adams, Katy M. E. Turner and Susie Huntington

Diagnostics 2023, 13(24), 3612; https://doi.org/10.3390/diagnostics13243612 - 6 Dec 2023

Viewed by 1305

Abstract

Detecting hypermethylation of tumour suppressor genes could provide an alternative to liquid-based cytology (LBC) triage within HPV primary cervical screening. The impact of using the QIAsure^® FAM19A4/mir124-2 DNA Methylation Test (QIAGEN, N.V, Hilden, Germany) on CIN3+ diagnoses, retention, unnecessary colposcopies, and programme costs is unknown. A decision-tree model was developed to compare LBC with the QIAsure Methylation testing to guide colposcopy referral. Incorporating clinician- and self-sampling pathways the model was informed by the Dutch cervical cancer screening programme, published studies, and manufacturer data. Clinical and cost outcomes were assessed using two scenarios for DNA methylation testing and LBC relative performance. Sensitivity analyses (deterministic and probabilistic) were performed to assess model and parameter uncertainty. A range of self-sampling uptake was assessed in scenario analyses. For the screening cohort (n = 807,269) where 22.1% self-sampled, the number of unnecessary colposcopies and CIN3+ diagnoses varied according to the relative performance of methylation testing and LBC. Irrespective of relative performance, the cost per complete screen was lower and fewer people were lost to follow-up when using DNA methylation testing. The results indicate that, within an HPV primary screening programme that incorporates self-sampling, using the QIAsure Methylation Test for triage reduces the cost per screen compared to LBC. Full article

(This article belongs to the Special Issue Cervical Cancer & Cervical Dysplasia: Screening, Diagnosis, and Treatment)

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10 pages, 603 KiB

Open AccessArticle

The Value of Four-Quadrant Cervical Biopsy in Women with Different Colposcopic Impressions

by Mandy Man-Yee Chu, Charleen Sze-Yan Cheung, Siew-Fei Ngu, Ka-Yu Tse, Philip Pun-Ching Ip, Annie Nga-Yin Cheung, Hextan Yuen-Sheung Ngan and Karen Kar-Loen Chan

Diagnostics 2023, 13(14), 2384; https://doi.org/10.3390/diagnostics13142384 - 16 Jul 2023

Viewed by 2765

Abstract

The aim of this study was to compare the diagnostic efficacy of colposcopic-directed biopsy and four-quadrant biopsy in detecting high-grade cervical intra-epithelial neoplasia (CIN). Women attending three women’s clinics for routine cervical screening were recruited. Colposcopy was arranged for women with any cytologic abnormalities greater than atypical squamous cells of undetermined significance (ASCUS), two consecutive ASCUS results or positive HPV testing. During colposcopy, a cervical biopsy was taken from the most suspicious area, but more than one biopsy was allowed. Four-quadrant biopsies at 3, 6, 9 and 12 o’clock and an endocervical curettage were also taken in all cases. A total of 1522 colposcopies were performed in 1311 subjects from June 2010 to August 2017, with 118 cases of high-grade CIN diagnosed. Colposcopic-directed biopsy detected 50.8% of the 118 high-grade CIN, while four-quadrant biopsy detected 86.4% (p < 0.0001). Twenty-seven cases (22.9%) of high-grade CIN were diagnosed in women with normal or unsatisfactory colposcopy. Among the 64 cases with low-grade colposcopic impression, four-quadrant biopsy detected significantly more high-grade CIN (53 cases, 82.8%) than colposcopic-directed biopsy (35 cases, 56.3%) (p = 0.0011). Four-quadrant cervical biopsies should be considered for all women with an abnormal smear or positive HPV testing, especially in patients with low-grade/normal/unsatisfactory colposcopy. Full article

(This article belongs to the Special Issue Cervical Cancer & Cervical Dysplasia: Screening, Diagnosis, and Treatment)

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11 pages, 2812 KiB

Open AccessArticle

Prognostic Utility of CD47 in Cancer of the Uterine Cervix and the Sensitivity of Immunohistochemical Scores

by Angel Yordanov, Velizar Shivarov, Stoyan Kostov, Yonka Ivanova, Polina Dimitrova, Savelina Popovska, Eva Tsoneva and Mariela Vasileva-Slaveva

Diagnostics 2023, 13(1), 52; https://doi.org/10.3390/diagnostics13010052 - 24 Dec 2022

Cited by 1 | Viewed by 1418

Abstract

Introduction: Cancer of the uterine cervix (CUC) is still one of the most frequent oncological diagnoses in women. The specific interactions between the tumor cells of CUC and the cells and tissues in the tumor microenvironment can affect cancer cells’ invasive and metastatic potential and can modulate tumor’s progression and death. CD47 is a trans-membranous immunoglobulin, expressed in many cells. It protects the cells from being destroyed by the circulating macrophages. Aim: We aimed to evaluate the prognostic role of CD47 expressed in the tumor tissues of patients with CUC for tumor progression and to find the most sensitive immunohistochemical score for defining the cut-off significantly associated with tumor biology and progression. Materials and methods: Paraffin-embedded tumor tissues from 86 patients with CUC were included in the study. Clinico-morphological data for patients, such as age and stage at diagnosis according to FIGO and TNM classification, were obtained from the hospital electronic medical records. Immunohistochemical staining was performed with rabbit recombinant monoclonal CD47 antibody (Clone SP279). The final result was interpreted based on three reporting models in immunohistochemistry: H-score, Allred score and combined score. Results: The expression of CD47 was higher in tumors limited in the cervix compared with those invading other structures, and it did not depend on the nodal status. The results of immunohistochemical staining were similar regardless of which immunohistochemical method was used. The most significant correlation with TNM stage was observed with the H-score (p = 0.00018). The association with the Allred and combined score was less significant, with p values of 0.0013 and 0.0002, respectively. Conclusion: The expression of CD47 in the cancer cells is prognostic for tumor invasion in the surrounding structures, independent of lymph node engagement. The H-score is the most sensitive immunohistochemical score to describe tumor stage. To the best of our knowledge, this is the first study evaluating the significance of CD47 expression in CUC. Full article

(This article belongs to the Special Issue Cervical Cancer & Cervical Dysplasia: Screening, Diagnosis, and Treatment)

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13 pages, 1984 KiB

Open AccessArticle

Concordance Rate of Colposcopy in Detecting Cervical Intraepithelial Lesions

by Frederik A. Stuebs, Anna K. Dietl, Annika Behrens, Werner Adler, Carol Geppert, Arndt Hartmann, Antje Knöll, Matthias W. Beckmann, Grit Mehlhorn, Carla E. Schulmeyer, Paul Gass and Martin C. Koch

Diagnostics 2022, 12(10), 2436; https://doi.org/10.3390/diagnostics12102436 - 8 Oct 2022

Cited by 7 | Viewed by 1964

Abstract

Background: The purpose of this research is to estimate the rate of concordance, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of colposcopy for high-grade squamous lesions and carcinomas (HSIL+). Methods: We conducted a retrospective study of colposcopies performed in the certified Dysplasia Unit in Erlangen between January 2015 and May 2022 (7.5 years). The colposcopic findings were correlated with biopsies obtained during examinations or surgery. Cases without histology were excluded. The primary outcome was the rate of concordance between the colposcopic and histological findings in relation to the type of transformation zone (TZ), examiner’s level of experience and age of the patients. Results: A total of 4778 colposcopies in 4001 women were analyzed. The rates of concordance for CIN I/LSIL, CIN II/HSIL, CIN III/HSIL, and carcinoma were 43.4%, 59.5%, 78.5%, and 53.9%, respectively. The rate of concordance was lowest for TZ3 and highest for colposcopists with more than 10 years’ experience. Conclusions: Colposcopy is an important, feasible, and effective method. Careful work-up needs to be performed for women with TZ3 who are over 35 years old, as they are at the highest risk of being misdiagnosed. The highest concordance for detecting HSIL+ was seen for colposcopists with >10 years’ experience. Full article

(This article belongs to the Special Issue Cervical Cancer & Cervical Dysplasia: Screening, Diagnosis, and Treatment)

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13 pages, 897 KiB

Open AccessArticle

Cytology and High-Risk Human Papillomavirus Test for Cervical Cancer Screening Assessment

by Frederik A. Stuebs, Martin C. Koch, Anna K. Dietl, Werner Adler, Carol Geppert, Arndt Hartmann, Antje Knöll, Matthias W. Beckmann, Grit Mehlhorn, Carla E. Schulmeyer and Paul Gass

Diagnostics 2022, 12(7), 1748; https://doi.org/10.3390/diagnostics12071748 - 19 Jul 2022

Cited by 8 | Viewed by 2005

Abstract

Background: A new nationwide screening strategy was implemented in Germany in January 2020. No data are available for women referred to certified dysplasia units for secondary clarification after primary diagnosis by a local physician. We therefore investigated combined testing with Papanicolaou smears and high-risk human papillomavirus (hrHPV) and compared the data with the final histological findings. Methods: Between January 2015 and October 2020, all referred women who underwent colposcopy of the uterine cervix in our certified dysplasia unit were included. Cytology findings were classified using the Munich III nomenclature. Results: A total of 3588 colposcopies were performed in 3118 women, along with Pap smear and hrHPV co-testing, followed by histology. Women with Pap II-p (ASC-US) and a positive hrHPV co-test had a 22.4% risk for cervical intraepithelial neoplasia (CIN) 3/high-grade squamous intraepithelial lesion (HSIL). The risk of CIN 3/HSIL was 83.8% in women with Pap IVa-p (HSIL) and a positive hrHPV co-test. A positive hrHPV co-test increased the risk for HSIL+ (OR 5.942; 95% CI, 4.617 to 7.649; p < 0.001) as compared to a negative hrHPV co-test. Conclusions: The accuracy of Pap smears is comparable with the screening results. A positive hrHPV test increases the risk for HSIL+ fivefold. Colposcopy is necessary to diagnose HSIL+ correctly. Full article

(This article belongs to the Special Issue Cervical Cancer & Cervical Dysplasia: Screening, Diagnosis, and Treatment)

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Review

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14 pages, 626 KiB

Open AccessReview

Enhancing Cervical Cancer Screening: Review of p16/Ki-67 Dual Staining as a Promising Triage Strategy

by Yung-Taek Ouh, Ho Yeon Kim, Kyong Wook Yi, Nak-Woo Lee, Hai-Joong Kim and Kyung-Jin Min

Diagnostics 2024, 14(4), 451; https://doi.org/10.3390/diagnostics14040451 - 19 Feb 2024

Cited by 2 | Viewed by 1498

Abstract

Cervical cancer, primarily caused by high-risk human papillomavirus (HR-HPV) types 16 and 18, is a major global health concern. Persistent HR-HPV infection can progress from reversible precancerous lesions to invasive cervical cancer, which is driven by the oncogenic activity of human papillomavirus (HPV) genes, particularly E6 and E7. Traditional screening methods, including cytology and HPV testing, have limited sensitivity and specificity. This review explores the application of p16/Ki-67 dual-staining cytology for cervical cancer screening. This advanced immunocytochemical method allows for simultaneously detecting p16 and Ki-67 proteins within cervical epithelial cells, offering a more specific approach for triaging HPV-positive women. Dual staining and traditional methods are compared, demonstrating their high sensitivity and negative predictive value but low specificity. The increased sensitivity of dual staining results in higher detection rates of CIN2+ lesions, which is crucial for preventing cervical cancer progression. However, its low specificity may lead to increased false-positive results and unnecessary biopsies. The implications of integrating dual staining into contemporary screening strategies, particularly considering the evolving landscape of HPV vaccination and changes in HPV genotype prevalence, are also discussed. New guidelines and further research are necessary to elucidate the long-term effects of integrating dual staining into screening protocols. Full article

(This article belongs to the Special Issue Cervical Cancer & Cervical Dysplasia: Screening, Diagnosis, and Treatment)

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