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Cancers
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Molecular Biology, Diagnosis and Management of Cervical Cancer
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Molecular Biology, Diagnosis and Management of Cervical Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: 31 August 2024 | Viewed by 8047

Special Issue Editors

Dr. Georgios Androutsopoulos

E-Mail Website
Guest Editor
Gynaecological Oncology Unit, Department of Obstetrics & Gynaecology School of Medicine, University of Patras, Patras, Greece
Interests: obstetrics—gynaecology; gynaecological oncology
Special Issues, Collections and Topics in MDPI journals
Dr. Georgios Michail

E-Mail Website
Guest Editor
Department of Obstetrics & Gynaecology, School of Medicine, University of Patras, Patras, Greece
Interests: obstetrics—gynaecology; gynaecological oncology; cervical pathology
Special Issues, Collections and Topics in MDPI journals
Dr. Thomas Vrekoussis

E-Mail Website
Guest Editor
Department of Obstetrics and Gynecology, Medical School, University Hospital of Crete, 715 00 Heraklion, Greece
Interests: obstetrics—gynaecology; gynaecological oncology
Special Issues, Collections and Topics in MDPI journals
Dr. George Valasoulis

E-Mail Website
Guest Editor
1. Department of Obstetrics and Gynaecology, University Hospital of Larisa, 41334 Larisa, Greece
2. Hellenic National Public Health Organization - ECDC, 15123 Athens, Greece
Interests: obstetrics – gynaecology; gynaecological oncology; cervical pathology

Special Issue Information

Dear Colleagues,

Cervical cancer (CC) is the most common malignancy of the female reproductive system and usually affects young women, sometimes before the completion of childbearing. The main aim of this Special Issue is the presentation of recent advances in molecular biology, diagnosis, and management of CC.

The primary CC treatment mainly depends on the disease stage and could be either surgical, non-surgical (radiotherapy, chemoradiotherapy), or a combination of both. Furthermore, surgical management of CC could be either conservative or radical. More specifically, a conservative surgical approach (cervical conization, radical trachelectomy) is mainly used in CC patients with early-stage disease and a strong desire for fertility preservation. Likewise, standard surgical treatment (radical hysterectomy) is preferred in CC patients with early-stage disease, who have already completed their childbearing. In contrast, the salvage surgical approach (pelvic exenteration, laterally extended endopelvic resection) is indicated in patients with locally advanced, persistent, or recurrent CC, who have already been treated with radiotherapy or chemo-radiotherapy.

In conclusion, early diagnosis and appropriate treatment planning have a direct effect on the quality of life and overall survival of CC patients. Moreover, the type of primary treatment and the extent of surgery should be carefully individualized according to disease stage, histologic subtype, fertility issues, and performance status.

Potential topics include, but are not limited to:

  • Preoperative evaluation,
  • Molecular biology,
  • Systematic surgical staging,
  • Pelvic and paraaortic lymph node dissection,
  • Sentinel lymph node mapping and dissection,
  • Systemic therapy,
  • Radiotherapy,
  • Fertility preservation,
  • Molecular targeted therapies.

Dr. Georgios Androutsopoulos
Dr. Georgios Michail
Dr. Thomas Vrekoussis
Dr. George Valasoulis
Guest Editors

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. Cancers 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 2900 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 cancer
  • molecular biology
  • lymph node dissection
  • sentinel lymph node mapping
  • sentinel lymph node dissection
  • surgery
  • systemic therapy
  • radiotherapy
  • fertility preservation
  • molecular targeted therapies

Published Papers (6 papers)

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Research

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12 pages, 3151 KiB  
Article
Prognostic Relevance of Tumor-Infiltrating Immune Cells in Cervix Squamous Cell Carcinoma
by Carl Mathis Wild, Fabian Garrido, Christian Dannecker, Melitta B. Köpke, Marie-Christine Chateau, Florence Boissière-Michot, Helene H. Heidegger, Aurelia Vattai, Mirjana Kessler, Udo Jeschke and Vincent Cavaillès
Cancers 2023, 15(20), 4952; https://doi.org/10.3390/cancers15204952 - 12 Oct 2023
Viewed by 961
Abstract
There exists a variety of studies about tumor-infiltrating immune cells (TIICs) in cervical cancer, but their prognostic value in correlation with the histopathological subtype has never been investigated. Therefore, the aim of this study was to quantify TIICs in a panel of 238 [...] Read more.
There exists a variety of studies about tumor-infiltrating immune cells (TIICs) in cervical cancer, but their prognostic value in correlation with the histopathological subtype has never been investigated. Therefore, the aim of this study was to quantify TIICs in a panel of 238 sporadic cervical cancers and investigate the correlation with cervical cancer subtype and patient survival. TIICs levels were significantly increased in the subgroup of CSCC (191 samples) in comparison to CAC (47 samples). In CSCC, TIICs’ infiltration showed a negative correlation with age, FIGO stage and with the histone protein modification H3K4me3. Moreover, in CAC, it was positively correlated with p16 and with the glucocorticoid receptor and inversely correlated with the MDM2 protein and with H3K4me3. Interestingly, immune infiltration was an independent positive prognosticator for disease-free survival (DFS) in patients with CSCC, those bearing tumors with the strongest TIICs infiltration showing the better DFS. Altogether, the present study provides a differentiated overview of the relations between TIIC levels and prognosis in patients with CSCC vs. patients with CAC. Full article
(This article belongs to the Special Issue Molecular Biology, Diagnosis and Management of Cervical Cancer)
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15 pages, 4035 KiB  
Article
Effects of Interfraction Dose Variations of Target and Organs at Risk on Clinical Outcomes in High Dose Rate Brachytherapy for Cervical Cancer
by Brien Washington, Dennis Cheek, Denise Fabian, Mahesh Kudrimoti, Damodar Pokhrel, Chi Wang, Cameron Thayer-Freeman and Wei Luo
Cancers 2023, 15(19), 4862; https://doi.org/10.3390/cancers15194862 - 5 Oct 2023
Viewed by 814
Abstract
Meeting dose prescription is critical to control tumors in radiation therapy. Interfraction dose variations (IDVs) from the prescribed dose in high dose rate brachytherapy (HDR) would cause the target dose to deviate from the prescription but their clinical effect has not been widely [...] Read more.
Meeting dose prescription is critical to control tumors in radiation therapy. Interfraction dose variations (IDVs) from the prescribed dose in high dose rate brachytherapy (HDR) would cause the target dose to deviate from the prescription but their clinical effect has not been widely discussed in the literature. Our previous study found that IDVs followed a left-skewed distribution. The clinical effect of the IDVs in 100 cervical cancer HDR patients will be addressed in this paper. An in-house Monte Carlo (MC) program was used to simulate clinical outcomes by convolving published tumor dose response curves with IDV distributions. The optimal dose and probability of risk-free local control (RFLC) were calculated using the utility model. The IDVs were well-fitted by the left-skewed Beta distribution, which caused a 3.99% decrease in local control probability and a 1.80% increase in treatment failure. Utility with respect to IDV uncertainty increased the RFLC probability by 6.70% and predicted an optimal dose range of 83 Gy–91 Gy EQD2. It was also found that a 10 Gy dose escalation would not affect toxicity. In conclusion, HRCTV IDV uncertainty reduced LC probabilities and increased treatment failure rates. A dose escalation may help mitigate such effects. Full article
(This article belongs to the Special Issue Molecular Biology, Diagnosis and Management of Cervical Cancer)
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13 pages, 631 KiB  
Article
Predictors of Non-Sentinel Lymph Node Metastasis in Patients with Positive Sentinel Lymph Node in Early-Stage Cervical Cancer: A SENTICOL GROUP Study
by Basile Pache, Matteo Tantari, Benedetta Guani, Patrice Mathevet, Laurent Magaud, Fabrice Lecuru and Vincent Balaya
Cancers 2023, 15(19), 4737; https://doi.org/10.3390/cancers15194737 - 26 Sep 2023
Cited by 1 | Viewed by 1170
Abstract
Background: The goal of this study was to identify the risk factors for metastasis in the remaining non-sentinel lymph nodes (SLN) in the case of positive SLN in early-stage cervical cancer. Methods: An ancillary analysis of two prospective multicentric databases on SLN biopsy [...] Read more.
Background: The goal of this study was to identify the risk factors for metastasis in the remaining non-sentinel lymph nodes (SLN) in the case of positive SLN in early-stage cervical cancer. Methods: An ancillary analysis of two prospective multicentric databases on SLN biopsy for cervical cancer (SENTICOL I and II) was performed. Patients with early-stage cervical cancer (FIGO 2018 IA to IIA1), with bilateral SLN detection and at least one positive SLN after ultrastaging, were included. Results: 405 patients were included in SENTICOL I and Il. Fifty-two patients had bilateral SLN detection and were found to have SLN metastasis. After pelvic lymphadenectomy, metastatic involvement of non-SLN was diagnosed in 7 patients (13.5%). Patients with metastatic non-SLN were older (51.9 vs. 40.8 years, p = 0.01), had more often lympho-vascular space invasion (LVSI) (85.7% vs. 35.6%, p = 0.03), and had more often parametrial involvement (42.9% vs. 6.7%, p = 0.003). Multivariate analysis retained age (OR = 1.16, 95% IC = [1.01–1.32], p = 0.03) and LVSI (OR = 25.97, 95% IC = [1.16–582.1], p = 0.04) as independently associated with non-SLN involvement. Conclusions: Age and LVSI seemed to be predictive of non-SLN metastasis in patients with SLN metastasis in early-stage cervical cancer. Larger cohorts are needed to confirm the results and clinical usefulness of such findings. Full article
(This article belongs to the Special Issue Molecular Biology, Diagnosis and Management of Cervical Cancer)
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8 pages, 814 KiB  
Article
Cost–Utility Analysis of Open Radical Hysterectomy Compared to Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer
by Nadav Michaan, Moshe Leshno, Gil Fire, Tamar Safra, Michal Rosenberg, Shira Peleg-Hasson, Dan Grisaru and Ido Laskov
Cancers 2023, 15(17), 4325; https://doi.org/10.3390/cancers15174325 - 29 Aug 2023
Viewed by 1089
Abstract
We aimed to investigate the cost-effectiveness of open surgery, compared to minimally invasive radical hysterectomy for early-stage cervical cancer, using updated survival data. Costs and utilities of each surgical approach were compared using a Markovian decision analysis model. Survival data stratified by surgical [...] Read more.
We aimed to investigate the cost-effectiveness of open surgery, compared to minimally invasive radical hysterectomy for early-stage cervical cancer, using updated survival data. Costs and utilities of each surgical approach were compared using a Markovian decision analysis model. Survival data stratified by surgical approach and surgery costs were received from recently published data. Average costs were discounted at 3%. The value of health benefits for each strategy was calculated using quality-adjusted life years (QALYs). Incremental cost-effectiveness ratio, calculated using the formula (average cost minimal invasive surgery—average cost open surgery)/(average QALY minimal invasive surgery—average QALY open surgery), was used for cost-effectiveness analysis. One-way sensitivity analysis was conducted for all variables. Open radical hysterectomy was found to be cost-saving compared to minimally invasive surgery with an incremental cost-effectiveness ratio of USD −66 and USD −373 for laparoscopic and robotic surgery, respectively. The most influential parameters in the model were surgery costs, followed by the disutility involved with open surgery. Until further data are generated regarding the survival of patients with early-stage cervical cancer treated by minimally invasive surgery, at current pricing, open radical hysterectomy is cost-saving compared to minimally invasive radical hysterectomy, both laparoscopic and robotic. Full article
(This article belongs to the Special Issue Molecular Biology, Diagnosis and Management of Cervical Cancer)
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Review

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20 pages, 1791 KiB  
Review
The Emerging Role of Histone Deacetylase Inhibitors in Cervical Cancer Therapy
by Iason Psilopatis, Nikolaos Garmpis, Anna Garmpi, Kleio Vrettou, Panagiotis Sarantis, Evangelos Koustas, Efstathios A. Antoniou, Dimitrios Dimitroulis, Gregory Kouraklis, Michail V. Karamouzis, Georgios Marinos, Konstantinos Kontzoglou, Afroditi Nonni, Konstantinos Nikolettos, Florian N. Fleckenstein, Christina Zoumpouli and Christos Damaskos
Cancers 2023, 15(8), 2222; https://doi.org/10.3390/cancers15082222 - 10 Apr 2023
Cited by 10 | Viewed by 2317
Abstract
Cervical carcinoma is one of the most common cancers among women globally. Histone deacetylase inhibitors (HDACIs) constitute anticancer drugs that, by increasing the histone acetylation level in various cell types, induce differentiation, cell cycle arrest, and apoptosis. The aim of the current review [...] Read more.
Cervical carcinoma is one of the most common cancers among women globally. Histone deacetylase inhibitors (HDACIs) constitute anticancer drugs that, by increasing the histone acetylation level in various cell types, induce differentiation, cell cycle arrest, and apoptosis. The aim of the current review is to study the role of HDACIs in the treatment of cervical cancer. A literature review was conducted using the MEDLINE and LIVIVO databases with a view to identifying relevant studies. By employing the search terms “histone deacetylase” and “cervical cancer”, we managed to identify 95 studies published between 2001 and 2023. The present work embodies the most up-to-date, comprehensive review of the literature centering on the particular role of HDACIs as treatment agents for cervical cancer. Both well-established and novel HDACIs seem to represent modern, efficacious anticancer drugs, which, alone or in combination with other treatments, may successfully inhibit cervical cancer cell growth, induce cell cycle arrest, and provoke apoptosis. In summary, histone deacetylases seem to represent promising future treatment targets in cervical cancer. Full article
(This article belongs to the Special Issue Molecular Biology, Diagnosis and Management of Cervical Cancer)
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Other

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16 pages, 1044 KiB  
Systematic Review
High- or Intermediate-Risk Histologic Features in Patients with Clinical Early-Stage Cervical Cancer Planned for Fertility-Sparing Surgery: A Systematic Review
by Janneke T. Wolswinkel, Mieke L. G. ten Eikelder, Cornelia G. Verhoef and Petra L. M. Zusterzeel
Cancers 2023, 15(15), 3920; https://doi.org/10.3390/cancers15153920 - 1 Aug 2023
Cited by 2 | Viewed by 1033
Abstract
Background: Fertility-sparing surgery (FSS) is a viable option for young women with early-stage cervical cancer (ECC); however, certain risk factors may necessitate additional treatments and impact fertility. This review examines the prevalence of these risk factors and available treatment options. Methods: A systematic [...] Read more.
Background: Fertility-sparing surgery (FSS) is a viable option for young women with early-stage cervical cancer (ECC); however, certain risk factors may necessitate additional treatments and impact fertility. This review examines the prevalence of these risk factors and available treatment options. Methods: A systematic search was conducted of studies including patients with ECC (IA1 with LVSI, IA2, IB1 (FIGO 2009)) who underwent FSS. Results: Sixty-four articles, comprising a total of 4118 women planned for FSS, were included. High- or intermediate-risk histologic features were found in 638 (15.5%) women: 5.1% had positive lymph node(s), 4.1% had positive resection margins, 0.3% had parametrial involvement, 1.0% had unspecified high-risk features, and 5.1% had intermediate-risk histology (primarily based on the Sedlis criteria). Adjuvant treatment impaired fertility in all women with adjuvant hysterectomy and/or (chemo)radiation (58.7%). Adjuvant chemotherapy was given to 1351 (32.8%) patients, which may reduce fertility. Conclusions: Fertility preservation could be achieved in most women; but high- or intermediate-risk factors necessitate more extensive surgery or radiotherapy leading to infertility. Adjuvant chemotherapy could be an alternative treatment option considering its effectiveness, safety and higher change in fertility preservation. The low incidence of parametrial involvement justifies waiving parametrectomy in tumors < 2 cm. Full article
(This article belongs to the Special Issue Molecular Biology, Diagnosis and Management of Cervical Cancer)
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