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Cancers
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Therapies in Cervical Cancer
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Therapies in Cervical Cancer

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

Deadline for manuscript submissions: closed (20 June 2022) | Viewed by 53818

Special Issue Editors

Dr. Raj Naik

E-Mail Website
Guest Editor
Queen Elizabeth Hospital, Gateshead, UK
Interests: gynaecological oncology; cervical cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Nick Wood

E-Mail Website
Guest Editor
Department of Gynaecological Oncology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK
Interests: sentinel lymph node assessment; fertility-sparing surgery; patient reported outcome measures
Dr. Antonios Anagnostopoulos

E-Mail Website
Guest Editor
Agios Savvas Cancer Hospital, Athens, Greece
Interests: minimal access surgery; surgical radicality and morbidity; follow-up strategies
Dr. Dennis Yiannakis

E-Mail Website
Guest Editor
Department of Gynaecological Oncology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK
Interests: chemotherapy; radiotherapy; biological therapies

Special Issue Information

Dear Colleagues,

Cervical cancer continues to be the fourth most frequent cancer in women with an estimated 570,000 new cases in 2018 representing 6.6% of all female cancers. Approximately 90% of deaths from cervical cancer occur in low- and middle-income countries. The high mortality rate from cervical cancer globally could be reduced through a comprehensive approach that includes prevention, early diagnosis, effective screening and treatment programs.

There have been significant advances in surgical treatment including minimal access surgery, less radical primary surgical treatment and sentinel node assessment resulting in significant reductions in post-treatment morbidity and the prospects of greater quality of life and after-care in long term survivors. Conversely, are the advances in increasing surgical radicality for the treatment of recurrent disease and the advent of the LEER (laterally extended endo-pelvic resection) procedure.

Equally important, have been the major developments in radiotherapy techniques including IMRT and more complex and advanced brachytherapy treatments providing the ability to completely sterilize the pelvis with reduced morbidity. Work is ongoing to improve the radiosensitisation offered by single agent cisplatin.  Advancing scientific knowledge of the disease is generating research in new chemotherapeutic agents, further angiogenesis inhibitors and DNA repair targeted agents. Promising early outcomes with immunotherapy are being further explored.

With so much which was once considered research now becoming standard clinical practices and in keeping with the “bench to clinic” concept and the explosion of personalized medicine we, the Guest Editors, are delighted to bring to you this Special Themed Edition of the journal “Cancers” focusing specifically on therapies in cervical cancer.

Dr. Raj Naik
Dr. Nick Wood
Dr. Antonios Anagnostopoulos
Dr. Dennis Yiannakis
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

  • cervix cancer
  • surgery
  • radiotherapy
  • chemotherapy
  • minimal access
  • sentinel node assessment

Published Papers (15 papers)

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Editorial

Jump to: Research

3 pages, 195 KiB  
Editorial
Therapies in Cervical Cancer—Editorial
by Raj Naik, Nick Wood, Antonios Anagnostopoulos and Dennis Yiannakis
Cancers 2023, 15(2), 537; https://doi.org/10.3390/cancers15020537 - 16 Jan 2023
Viewed by 1250
Abstract
George Papanikolaou is famously quoted as saying “the first observation of cancer cells in the smear of the uterine cervix gave me one of the greatest thrills I ever experienced during my scientific career” [...] Full article
(This article belongs to the Special Issue Therapies in Cervical Cancer)

Research

Jump to: Editorial

21 pages, 4370 KiB  
Article
Determining the Potential of DNA Damage Response (DDR) Inhibitors in Cervical Cancer Therapy
by Santu Saha, Stuart Rundle, Ioannis C. Kotsopoulos, Jacob Begbie, Rachel Howarth, Isabel Y. Pappworth, Asima Mukhopadhyay, Ali Kucukmetin, Kevin J. Marchbank and Nicola Curtin
Cancers 2022, 14(17), 4288; https://doi.org/10.3390/cancers14174288 - 1 Sep 2022
Cited by 6 | Viewed by 2272
Abstract
Cisplatin-based chemo-radiotherapy (CRT) is the standard treatment for advanced cervical cancer (CC) but the response rate is poor (46–72%) and cisplatin is nephrotoxic. Therefore, better treatment of CC is urgently needed. We have directly compared, for the first time, the cytotoxicity of four [...] Read more.
Cisplatin-based chemo-radiotherapy (CRT) is the standard treatment for advanced cervical cancer (CC) but the response rate is poor (46–72%) and cisplatin is nephrotoxic. Therefore, better treatment of CC is urgently needed. We have directly compared, for the first time, the cytotoxicity of four DDR inhibitors (rucaparib/PARPi, VE-821/ATRi, PF-477736/CHK1i and MK-1775/WEE1i) as single agents, and in combination with cisplatin and radiotherapy (RT) in a panel of CC cells. All inhibitors alone caused concentration-dependent cytotoxicity. Low ATM and DNA-PKcs levels were associated with greater VE-821 cytotoxicity. Cisplatin induced ATR, CHK1 and WEE1 activity in all of the cell lines. Cisplatin only activated PARP in S-phase cells, but RT activated PARP in the entire population. Rucaparib was the most potent radiosensitiser and VE-821 was the most potent chemosensitiser. VE-821, PF-47736 and MK-1775 attenuated cisplatin-induced S-phase arrest but tended to increase G2 phase accumulation. In mice, cisplatin-induced acute kidney injury was associated with oxidative stress and PARP activation and was prevented by rucaparib. Therefore, while all inhibitors investigated may increase the efficacy of CRT, the greatest clinical potential of rucaparib may be in limiting kidney damage, which is dose-limiting. Full article
(This article belongs to the Special Issue Therapies in Cervical Cancer)
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11 pages, 812 KiB  
Article
Combined Liquid Biopsy Methylation Analysis of CADM1 and MAL in Cervical Cancer Patients
by Markus Leffers, Johanna Herbst, Jolanthe Kropidlowski, Katharina Prieske, Anna Lena Bohnen, Sven Peine, Anna Jaeger, Leticia Oliveira-Ferrer, Yvonne Goy, Barbara Schmalfeldt, Klaus Pantel, Linn Wölber, Katharina Effenberger and Harriet Wikman
Cancers 2022, 14(16), 3954; https://doi.org/10.3390/cancers14163954 - 16 Aug 2022
Cited by 5 | Viewed by 3030
Abstract
Cervical cancer is the fourth most common cancer in women, which is associated in >95% with a high-risk human papillomavirus (HPV) infection. Methylation of specific genes has been closely associated with the progress of cervical high-grade dysplastic lesions to invasive carcinomas. Therefore, DNA [...] Read more.
Cervical cancer is the fourth most common cancer in women, which is associated in >95% with a high-risk human papillomavirus (HPV) infection. Methylation of specific genes has been closely associated with the progress of cervical high-grade dysplastic lesions to invasive carcinomas. Therefore, DNA methylation has been proposed as a triage for women infected with high-risk HPV. Methylation analyses of cervical cancer tissue have shown that cell adhesion molecule 1 (CADM1) and myelin and lymphocyte protein (MAL) methylation are present in over 90% of all cervical high-grade neoplasias and invasive cervical cancers. Here, we established a liquid biopsy-based assay to detect MAL and CADM1 methylation in cell free (cf)DNA of cervical cancer. Methylation of the target gene was validated on bisulfite converted smear-DNA from cervical dysplasia patients and afterward applied to cfDNA using quantitative real-time PCR. In 52 smears, a combined analysis of CADM1 and/or MAL (CADM1/MAL) showed methylation in 86.5% of the cases. In cfDNA samples of 24 cervical cancer patients, CADM1/MAL methylation was detected in 83.3% of the cases. CADM1/MAL methylation was detected already in 81.8% of stage I-II patients showing the high sensitivity of this liquid biopsy assay. In combination with a specificity of 95.5% towards healthy donors (HD) and an area under the curve (AUC) of 0.872 in the receiver operating characteristic (ROC) analysis, CADM1/MAL cfDNA methylation detection might represent a novel and promising liquid biopsy marker in cervical cancer. Full article
(This article belongs to the Special Issue Therapies in Cervical Cancer)
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15 pages, 317 KiB  
Article
Effect of Condom Use after CIN Treatment on Cervical HPV Biomarkers Positivity: Prolonged Follow Up Study
by George Valasoulis, Georgios Michail, Abraham Pouliakis, Georgios Androutsopoulos, Ioannis. G. Panayiotides, Maria Kyrgiou, Alexandros Daponte and Evangelos Paraskevaidis
Cancers 2022, 14(14), 3530; https://doi.org/10.3390/cancers14143530 - 20 Jul 2022
Cited by 5 | Viewed by 2187
Abstract
Background: Several factors contribute in the cervical healing process following local surgical treatment; in a previous work our group has documented a beneficial mid-term role of regular condom use immediately postoperatively in terms of CIN relapse prevention and expression of active viral biomarkers. [...] Read more.
Background: Several factors contribute in the cervical healing process following local surgical treatment; in a previous work our group has documented a beneficial mid-term role of regular condom use immediately postoperatively in terms of CIN relapse prevention and expression of active viral biomarkers. Materials and Methods: Aiming to investigate whether the favorable contribution of consistent condom use could be extrapolated in the longer term, we conducted a prospective single center observational study including women scheduled to undergo conservative excisional treatment for CIN (LLETZ procedure). In all women a strong recommendation for consistent use for the first 6 months was given. For 204 women who underwent the procedure and completed successfully the two-year follow up a complete dataset of HPV biomarkers’ results obtained six months and two years postoperatively was available. Patients were asked to complete a questionnaire to assess condom use compliance. A 90% compliance rate represented the threshold for consistent use. An LBC sample was obtained and tested for HPV genotyping, E6 & E7 mRNA by NASBA technique as well as flow cytometry, and p16 at 0 (pre-treatment), 6 and 24 months. HPV DNA and other related biomarkers status at 6 and 24 months, treatment failures at 24 months and condom use compliance rates represented study outcomes. Results: Six months post-operatively we documented a reduction in the rates of HPV DNA positivity, which was detected in only 23.2% of compliant condom users in comparison to 61.9% in the non-compliant group (p < 0.001, OR: 0.19, 95%CI: 0.1–0.36). For the HPV mRNA test, either assessed with the NASBA method or with flow cytometry, reduced positivity percentages were observed in the compliant group, in particular 1.6% vs. 8% for NASBA and 7.1% vs. 16.4% using flow cytometry, although these differences were not statistically significant (p = 0.1039 and 0.0791, respectively). Finally, reduced p16 positivity rates were documented in the compliant group. At the two year follow up, a more pronounced difference in HPV DNA positivity rates was observed, specifically only 13% positivity among the compliant women compared with 71% of the non-compliant (p < 0.0001); this illustrates a further decreasing trend compared with the 6th month in the compliant group as opposed to an increasing tendency in the non-compliant group, respectively (difference: 9.0%, 95% CI: 0% to 20.6%, p = 0.1523). At that time, 80% of the failed treatments were HPV mRNA positive compared to 10% positivity for the cases treated successfully (OR: 34, 95%CI: 6.8–173, p < 0.0001), a finding indicative that HPV mRNA E6 & E7 positivity accurately predicts treatment failure; p16 positivity was also observed at higher rates in cases with treatment failure. Conclusions: Consistent condom use following conservative excisional CIN treatment appears to significantly reduce rates of CIN recurrence and biomarkers of HPV expression. Additional HPV vaccination at the time of treatment could further enhance the positive effect of consistent condom use. Full article
(This article belongs to the Special Issue Therapies in Cervical Cancer)
12 pages, 2070 KiB  
Article
3D-Image-Guided Multi-Catheter Interstitial Brachytherapy for Bulky and High-Risk Stage IIB–IVB Cervical Cancer
by Tetsuya Kokabu, Koji Masui, Yosuke Tarumi, Naoki Noguchi, Kohei Aoyama, Hisashi Kataoka, Hiroshi Matsushima, Kaori Yoriki, Daisuke Shimizu, Hideya Yamazaki, Kei Yamada and Taisuke Mori
Cancers 2022, 14(5), 1257; https://doi.org/10.3390/cancers14051257 - 28 Feb 2022
Cited by 10 | Viewed by 3901
Abstract
This study aimed to evaluate the efficacy and safety of computed tomography-magnetic resonance imaging (CT-MRI)-guided multi-catheter interstitial brachytherapy for patients with bulky (≥4 cm) and high-risk, stage IIB–IVB advanced cervical cancer. Eighteen patients who underwent concurrent chemoradiotherapy with multi-catheter interstitial brachytherapy between September [...] Read more.
This study aimed to evaluate the efficacy and safety of computed tomography-magnetic resonance imaging (CT-MRI)-guided multi-catheter interstitial brachytherapy for patients with bulky (≥4 cm) and high-risk, stage IIB–IVB advanced cervical cancer. Eighteen patients who underwent concurrent chemoradiotherapy with multi-catheter interstitial brachytherapy between September 2014 and August 2020 were enrolled. The prescribed dose of external beam radiotherapy was 45–50.4 Gy, and the brachytherapy high-dose-rate aim was 25–30 Gy per 5 fractions. The endpoints were four-year local and pelvic control rates, four-year disease-free and overall survival rates, and the adverse events rate. The median follow-up period was 48.4 months (9.1–87.5 months). Fifteen patients received concurrent cisplatin therapy (40 mg/m2, q1week). Four (22.2%), seven (38.9%), and seven (38.9%) patients had stage II, III, and IV cervical cancer, respectively. Pelvic and para-aortic lymph node metastases were observed in 11 (61.1%) and 2 (11.1%) patients, respectively. The median pre-treatment volume was 87.5 cm3. The four-year local control, pelvic control, disease-free survival, and overall survival rates were 100%, 100%, 81.6%, and 87.8%, respectively. Three (16.7%) patients experienced grade 3 adverse events, and none experienced grade 4–5 adverse events. CT-MRI-guided multi-catheter interstitial brachytherapy could be a promising treatment strategy for locally advanced cervical cancer. Full article
(This article belongs to the Special Issue Therapies in Cervical Cancer)
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12 pages, 1217 KiB  
Article
The Impact of Surgical Practice on Oncological Outcomes in Robot-Assisted Radical Hysterectomy for Early-Stage Cervical Cancer, Spanish National Registry
by Sergi Fernandez-Gonzalez, Jordi Ponce, María Ángeles Martínez-Maestre, Marc Barahona, Natalia R. Gómez-Hidalgo, Berta Díaz-Feijoo, Andrea Casajuana, Myriam Gracia, Jon Frias-Gomez, Yolanda Benavente, Laura Costas, Lola Martí, Lidia Melero, Jose Manuel Silvan, Eva Beiro, Ignacio Lobo, Jesús De la Rosa, Pluvio J. Coronado and Antonio Gil-Moreno
Cancers 2022, 14(3), 698; https://doi.org/10.3390/cancers14030698 - 29 Jan 2022
Cited by 5 | Viewed by 2171
Abstract
This study aimed to assess whether surgical practice had a significant impact on oncological outcomes among women who underwent robot-assisted radical hysterectomy for early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009). The secondary objective was to audit the pre-surgical quality indicators (QI) proposed [...] Read more.
This study aimed to assess whether surgical practice had a significant impact on oncological outcomes among women who underwent robot-assisted radical hysterectomy for early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009). The secondary objective was to audit the pre-surgical quality indicators (QI) proposed by the European Society of Gynaecological Oncology (ESGO). The top 5 of 10 centers in Spain and Portugal were included in the analysis. The hospitals were divided into group A (n = 118) and group B (n = 97), with recurrence rates of <10% and >10%, respectively. After balancing both groups using the propensity score, the ORs for all events were higher and statistically significant for group B (recurrences OR = 1.23, 95% CI = 1.13–1.15, p-value = 0.001; death OR = 1.10, 95% CI = 1.02–1.18, p-value = 0.012; disease-specific mortality ORr = 1.11, 95% CI = 1.04–1.19, p-value = 0.002). A higher surgical volume, higher participation in clinical trials, higher rate of MRI use for diagnosis, greater use of sentinel lymph node biopsies, and a favorable learning curve with low rates of early recurrences were observed among the centers with better oncological outcomes. These factors might have a significant impact on oncological outcomes not only after robot-assisted surgery, but also after laparoscopies and open surgeries in the treatment of cervical cancer. Full article
(This article belongs to the Special Issue Therapies in Cervical Cancer)
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11 pages, 627 KiB  
Article
Risk Factors for Recurrence after Robot-Assisted Radical Hysterectomy for Early-Stage Cervical Cancer: A Multicenter Retrospective Study
by Jordi Ponce, Sergi Fernandez-Gonzalez, Antonio Gil-Moreno, Pluvio J. Coronado, Jesús De la Rosa, Henrique Nabais, Ginés Hernández, Anna Taltavull, Juan Gilabert-Estelles, Sergio Martínez-Román, Manel Barahona, Marc Barahona and María Ángeles Martínez-Maestre
Cancers 2020, 12(11), 3387; https://doi.org/10.3390/cancers12113387 - 16 Nov 2020
Cited by 7 | Viewed by 2205
Abstract
This retrospective analysis aimed to assess the risk factors for recurrence in patients diagnosed with early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009) undergoing robot-assisted radical hysterectomy in Spain and Portugal between 2009 and 2018. A second primary objective was to audit the [...] Read more.
This retrospective analysis aimed to assess the risk factors for recurrence in patients diagnosed with early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009) undergoing robot-assisted radical hysterectomy in Spain and Portugal between 2009 and 2018. A second primary objective was to audit the oncological outcomes according to quality indicators (QI) proposed by the European Society of Gynecology Oncology (ESGO). The study population included 239 women. After a median follow-up of 51 months, recurrence occurred in 26 patients (10.9%). Independent factors for recurrence were clinical tumor size > 20 mm (hazard ratio (HR) 2.37), adenocarcinoma as histological type (HR 2.51), positive pelvic lymph nodes (HR 4.83), tumor grade 2 (HR 4.99), tumor grade 3 (HR 8.06), and having not performed sentinel lymph node biopsy (SLNB) (HR 4.08). All 5 QI selected were surpassed by our results. In patients with early-stage cervical cancer undergoing robotic radical hysterectomy, clinicians should be aware that tumor grade 2 and 3, tumor size > 20 mm, adenocarcinoma, positive pelvic nodes, and lack of performance of SLNB are risk factors for recurrence. Fulfillment of QI targets of the ESGO might be considered as an objective oncological outcome indicator supporting the minimally invasive approach for early-stage cervical cancer treatment. Full article
(This article belongs to the Special Issue Therapies in Cervical Cancer)
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10 pages, 8700 KiB  
Article
A Concise Paradigm on Radical Hysterectomy: The Comprehensive Anatomy of Parametrium, Paracolpium and the Pelvic Autonomic Nerve System and Its Surgical Implication
by Mustafa Zelal Muallem, Thomas Jöns, Nadja Seidel, Jalid Sehouli, Yasser Diab and Denis Querleu
Cancers 2020, 12(7), 1839; https://doi.org/10.3390/cancers12071839 - 8 Jul 2020
Cited by 14 | Viewed by 6354
Abstract
The current understanding of radical hysterectomy is more centered on the uterus and little is discussed regarding the resection of the vaginal cuff and the paracolpium as an essential part of this procedure. The anatomic dissections of two fresh and 17 formalin-fixed female [...] Read more.
The current understanding of radical hysterectomy is more centered on the uterus and little is discussed regarding the resection of the vaginal cuff and the paracolpium as an essential part of this procedure. The anatomic dissections of two fresh and 17 formalin-fixed female pelvis cadavers were utilized to understand and decipher the anatomy of the pelvic autonomic nerve system (PANS) and its connections to the surrounding anatomical structures, especially the paracolpium. The study mandates the recognition of the three-dimensional (3D) anatomic template of the parametrium and paracolpium and provides herewith an enhanced scope during a nerve-sparing radical hysterectomy procedure by precise description of the paracolpium and its close anatomical relationships to the components of the PANS. This enables the medical fraternity to distinguish between direct infiltration of the paracolpium, where the nerve sparing technique is no longer possible, and the affected lymph node in the paracolpium, where nerve sparing is still an option. This study gives rise to a tailored surgical option that allows for abandoning the resection of the paracolpium by FIGO stage IB1, where less than 2 cm vaginal vault resection is demanded. Full article
(This article belongs to the Special Issue Therapies in Cervical Cancer)
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10 pages, 2180 KiB  
Article
FIGO 2018 Staging for Cervical Cancer: Influence on Stage Distribution and Outcomes in the 3D-Image-Guided Brachytherapy Era
by Kento Tomizawa, Takuya Kaminuma, Kazutoshi Murata, Shin-ei Noda, Daisuke Irie, Takuya Kumazawa, Takahiro Oike and Tatsuya Ohno
Cancers 2020, 12(7), 1770; https://doi.org/10.3390/cancers12071770 - 2 Jul 2020
Cited by 19 | Viewed by 4594
Abstract
Recent widespread use of three-dimensional image-guided brachytherapy (3D-IGBT) has improved radiotherapy outcomes of cervical cancer dramatically. In 2018, the International Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer was revised. However, the influence of the revisions on the stage distribution [...] Read more.
Recent widespread use of three-dimensional image-guided brachytherapy (3D-IGBT) has improved radiotherapy outcomes of cervical cancer dramatically. In 2018, the International Federation of Gynecology and Obstetrics (FIGO) staging system for cervical cancer was revised. However, the influence of the revisions on the stage distribution and outcomes of cervical cancers treated with 3D-IGBT remains unclear. Here, we retrospectively analyzed 221 patients with cervical squamous cell carcinoma treated with definitive radiotherapy using 3D-IGBT (median follow-up, 60 months). The stage distribution and outcomes were compared between the 2009 and 2018 schemas. Stage migration occurred in 52.9% of the patients. Patients classified with the 2018 criteria as stage IIICr had the highest proportion (43.8%) of migration, and were mainly from the 2009 stages IIB and IIIB. The 2009 and 2018 schemas showed comparable performance at stratifying 5-year overall survival (OS) and 5-year progression-free survival (PFS) for patients in stages IB–IVA. The 2018 criteria effectively stratified 5-year OS and PFS in the stage III substages. The 5-year OS and PFS for stage IIIC1r patients varied according to tumor T stage. These data provide evidence for the utility of the revised 2018 FIGO staging system in the clinical management of cervical cancers in the 3D-IGBT era. Full article
(This article belongs to the Special Issue Therapies in Cervical Cancer)
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14 pages, 449 KiB  
Article
Micrometastases in Sentinel Lymph Nodes Represent a Significant Negative Prognostic Factor in Early-Stage Cervical Cancer: A Single-Institutional Retrospective Cohort Study
by Roman Kocian, Jiri Slama, Daniela Fischerova, Anna Germanova, Andrea Burgetova, Ladislav Dusek, Pavel Dundr, Kristyna Nemejcova, Jiri Jarkovsky, Silvie Sebestova, Filip Fruhauf, Lukas Dostalek, Tereza Ballaschova and David Cibula
Cancers 2020, 12(6), 1438; https://doi.org/10.3390/cancers12061438 - 31 May 2020
Cited by 23 | Viewed by 3450
Abstract
The data on the prognostic significance of low volume metastases in lymph nodes (LN) are inconsistent. The aim of this study was to retrospectively analyze the outcome of a large group of patients treated with sentinel lymph node (SLN) biopsy at a single [...] Read more.
The data on the prognostic significance of low volume metastases in lymph nodes (LN) are inconsistent. The aim of this study was to retrospectively analyze the outcome of a large group of patients treated with sentinel lymph node (SLN) biopsy at a single referral center. Patients with cervical cancer, stage T1a-T2b, common tumor types, negative LN on preoperative staging, treated by primary surgery between 01/2007 and 12/2016, with at least unilateral SLN detection were included. Patients with abandoned radical surgery due to intraoperative SLN positivity detected by frozen section were excluded. All SLNs were postoperatively processed by an intensive protocol for pathological ultrastaging. Altogether, 226 patients were analyzed. Positive LN were detected in 38 (17%) cases; macrometastases (MAC), micrometastases (MIC), isolated tumor cells (ITC) in 14, 16, and 8 patients. With the median follow-up of 65 months, 22 recurrences occurred. Disease-free survival (DFS) reached 90% in the whole group, 93% in LN-negative cases, 89% in cases with MAC, 69% with MIC, and 87% with ITC. The presence of MIC in SLN was associated with significantly decreased DFS and OS. Patients with MIC and MAC should be managed similarly, and SLN ultrastaging should become an integral part of the management of patients with early-stage cervical cancer. Full article
(This article belongs to the Special Issue Therapies in Cervical Cancer)
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16 pages, 676 KiB  
Article
Alterations of HPV-Related Biomarkers after Prophylactic HPV Vaccination. A Prospective Pilot Observational Study in Greek Women
by George Valasoulis, Abraham Pouliakis, George Michail, Christine Kottaridi, Aris Spathis, Maria Kyrgiou, Evangelos Paraskevaidis and Alexandros Daponte
Cancers 2020, 12(5), 1164; https://doi.org/10.3390/cancers12051164 - 5 May 2020
Cited by 26 | Viewed by 2886
Abstract
The objective of this study was to investigate the hypothesis that HPV vaccination administered in patients with low-grade (LG) cytology shortly after an initial colposcopic assessment could prospectively alter HPV-related biomarkers. This was a prospective pilot observational study involving women attending a colposcopy [...] Read more.
The objective of this study was to investigate the hypothesis that HPV vaccination administered in patients with low-grade (LG) cytology shortly after an initial colposcopic assessment could prospectively alter HPV-related biomarkers. This was a prospective pilot observational study involving women attending a colposcopy clinic for evaluation of abnormal LG cytology that were advised to undergo HPV vaccination and proceeded accordingly. These women were compared with a matched unvaccinated group. Women requiring cervical biopsies or CIN treatment were excluded. Intervention: A full three-dose HPV vaccination was undertaken with either the 2-valent or the 4-valent anti-HPV VLP vaccine. LBC samples were obtained prior and after the completion of the vaccination regimen and tested for HPV DNA genotyping (CLART-2 HPV test) and E6 and E7 mRNA (NASBA technique). Results: Alterations of HPV-related biomarkers at a colposcopy reassessment appointment 12 months later. Analysis: The p-values, relative risk (RR), absolute relative risk (ARR), number needed to treat (NNT) and 95% confidence intervals for each biomarker in each group were assessed. Results: A total of 309 women were included in the analysis. One hundred fifty-two women received the vaccine. HPV vaccination reduced in a statistically significant manner (p < 0.05) HPV DNA positivity rates for genotypes 16, 18, and 31, RR = 1.6 (95% CI: 1.1 to 2.3), RR = 1.7 (95% CI: 1.1 to 2.8), and RR = 1.8 (95% CI: 1.0 to 2.9), in women who only tested DNA-positive for HPV16, 18, and 31 genotypes, respectively, prior to vaccination. A less pronounced, statistically insignificant reduction was shown for women who tested positive for both HPV DNA and mRNA E6 and E7 expression for HPV16, 18, and 33 subtypes. Statistically significant reduction in HPV mRNA positivity was solely documented for genotype 31 (p = 0.0411). Conclusions: HPV vaccination appears to significantly affect the rates of HPV16, 18, and 31 DNA-positive infections in the population testing HPV DNA-positive for the aforementioned genotypes. The above findings deserve verification in larger cohorts. Full article
(This article belongs to the Special Issue Therapies in Cervical Cancer)
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13 pages, 811 KiB  
Article
Central Pathology Review in SENTIX, a Prospective Observational International Study on Sentinel Lymph Node Biopsy in Patients with Early-Stage Cervical Cancer (ENGOT-CX2)
by Kristyna Nemejcova, Roman Kocian, Christhardt Kohler, Jiri Jarkovsky, Jaroslav Klat, Alberto Berjon, Radovan Pilka, Borek Sehnal, Blanca Gil-Ibanez, Ezequiel Lupo, Almerinda Petiz, Octavio Arencibia Sanchez, Peter Kascak, Fabio Martinelli, Alessandro Buda, Jiri Presl, Marc Barahona, Luc van Lonkhuijzen, Wiktor Szatkowski, Lubos Minar, Maja Pakiz, Pavel Havelka, Cristina Zorrero, Marcin Misiek, Leon Cornelius Snyman, Dariusz Wydra, Ignace Vergote, Alla Vinnytska, Mikulas Redecha, Martin Michal, Solveig Tingulstad, Barbara Kipp, Grzegorz Szewczyk, Robert Toth, Francisco Javier de Santiago Garcia, Pluvio Jesus Coronado Martin, Robert Poka, Karl Tamussino, Mathieu Luyckx, Maxime Fastrez, Juan Carlos Staringer, Anna Germanova, Andrea Plaikner, Sylva Bajsova, Pavel Dundr, Nina Mallmann-Gottschalk and David Cibulaadd Show full author list remove Hide full author list
Cancers 2020, 12(5), 1115; https://doi.org/10.3390/cancers12051115 - 29 Apr 2020
Cited by 5 | Viewed by 3690
Abstract
The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European [...] Read more.
The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European Network of Gynaecological Oncological Trial (ENGOT)-CX2 study. All specimens from at least two patients per site were submitted for the central review. For cases with major or critical deviations, the sites were requested to submit all samples from all additional patients for second-round assessment. From the group of 300 patients, samples from 83 cases from 37 sites were reviewed in the first round. Minor, major, critical, and no deviations were identified in 28%, 19%, 14%, and 39% of cases, respectively. Samples from 26 patients were submitted for the second-round review, with only two major deviations found. In conclusion, a high rate of major or critical deviations was identified in the first round of the central pathology review (28% of samples). This reflects a substantial heterogeneity in current practice, despite trial protocol requirements. The importance of the central review conducted prospectively at the early phase of the trial is demonstrated by a substantial improvement of SLN ultrastaging quality in the second-round review. Full article
(This article belongs to the Special Issue Therapies in Cervical Cancer)
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11 pages, 2537 KiB  
Article
Single Radiotherapy Fraction with Local Anti-CD40 Therapy Generates Effective Abscopal Responses in Mouse Models of Cervical Cancer
by Jana Wood, Sayeda Yasmin-Karim, Romy Mueller, Akila N. Viswanathan and Wilfred Ngwa
Cancers 2020, 12(4), 1026; https://doi.org/10.3390/cancers12041026 - 22 Apr 2020
Cited by 14 | Viewed by 3477
Abstract
Current treatment options for advanced cervical cancer are limited, especially for patients in poor-resource settings, with a 17% 5-year overall survival rate. Here, we report results in animal models of advanced cervical cancer, showing that anti-CD40 therapy can effectively boost the abscopal effect, [...] Read more.
Current treatment options for advanced cervical cancer are limited, especially for patients in poor-resource settings, with a 17% 5-year overall survival rate. Here, we report results in animal models of advanced cervical cancer, showing that anti-CD40 therapy can effectively boost the abscopal effect, whereby radiotherapy of a tumor at one site can engender therapeutically significant responses in tumors at distant untreated sites. In this study, two subcutaneous cervical cancer tumors representing one primary and one metastatic tumor were generated in each animal. Only the primary tumor was treated and the responses of both tumors were monitored. The study was repeated as a function of different treatment parameters, including radiotherapy dose and dosing schedule of immunoadjuvant anti-CD40. The results consistently suggest that one fraction dose of radiotherapy with a single dose of agonistic anti-CD40 can generate highly effective abscopal responses, with a significant increase in animal survival (p = 0.0004). Overall, 60% of the mice treated with this combination showed long term survival with complete tumor regression, where tumors of mice in other cohorts continued to grow. Moreover, re-challenged responders to the treatment developed vitiligo, suggesting developed immune memory for this cancer. The findings offer a potential new therapy approach, which could be further investigated and developed for the treatment of advanced cervical cancer, with major potential impact, especially in resource-poor settings. Full article
(This article belongs to the Special Issue Therapies in Cervical Cancer)
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14 pages, 24578 KiB  
Article
Nerve Sparing Radical Hysterectomy: Short-Term Oncologic, Surgical, and Functional Outcomes
by Mustafa Zelal Muallem, Robert Armbrust, Jörg Neymeyer, Andrea Miranda and Jumana Muallem
Cancers 2020, 12(2), 483; https://doi.org/10.3390/cancers12020483 - 19 Feb 2020
Cited by 24 | Viewed by 9076
Abstract
There is an obvious prevalence of disparity in opinions concerning the technique of nerve-sparing radical hysterectomy and its application, despite agreement on the need to spare the pelvic autonomic nerve system during such a radical operation. Understanding the precise three-dimensional anatomy of paracolpium [...] Read more.
There is an obvious prevalence of disparity in opinions concerning the technique of nerve-sparing radical hysterectomy and its application, despite agreement on the need to spare the pelvic autonomic nerve system during such a radical operation. Understanding the precise three-dimensional anatomy of paracolpium and its close anatomical relationship to the components of the pelvic autonomic nervous system is the key in performing the nerve-sparing radical hysterectomy. A total of 42 consecutive patients with primary cervical cancers, who were operated upon in our institution between January 2017 and June 2019, were analyzed, concerning surgical, urinary functional, and short-term oncologic outcomes. Two thirds of the patients had locally advanced tumors (T > 40 mm or pT ≥ IIA2) with a median tumor size of 44.1 mm. The nerve-sparing radical hysterectomy was combined with the complete recovery of bladder function in 90% of patients directly after surgery and in 97% of patients in the first 2 weeks. The recurrence rate in a median follow-up time of 18 months was 9.5%. The nerve-sparing radical hysterectomy approach, which depends on the comprehensive understanding of the precise entire anatomy of paracolpium, was found to be feasible and applicable, even in locally advanced tumors, with good functional results and convincing short-term oncologic outcomes. Full article
(This article belongs to the Special Issue Therapies in Cervical Cancer)
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8 pages, 227 KiB  
Article
Are Older Patients with Cervical Cancer Managed Differently to Younger Patients? An International Survey
by Maxime Frelaut, Nienke De Glas, Ignacio Zapardiel, Orit Kaidar-Person, Maria Kfoury, Benoit You, Susana Banerjee, Etienne Brain, Claire Falandry and Manuel Rodrigues
Cancers 2019, 11(12), 1955; https://doi.org/10.3390/cancers11121955 - 6 Dec 2019
Cited by 7 | Viewed by 2093
Abstract
Although a quarter of cervical cancers occur after the age of 65 years, there is no treatment consensus for these patients. The aim of this work was to survey how physicians treat patients with advanced cervical cancer, focusing on treatment adjustments according to [...] Read more.
Although a quarter of cervical cancers occur after the age of 65 years, there is no treatment consensus for these patients. The aim of this work was to survey how physicians treat patients with advanced cervical cancer, focusing on treatment adjustments according to age and frailty status. Specialists were invited to an online survey. Data collected included information on respondent and treatment strategy in four cases (FIGO IIb, FIGO IVa, FIGO IVb, metastatic recurrence) with three age scenarios (45-year-old, 75-year-old and fit, 75-year-old and unfit). We received 237 responses of which 117 were fully completed. Thirty-four percent of respondents reported they had available access to a geriatric team and 25% used a frailty screening tool in routine. Therapeutic strategies did not differ between young and old fit patients. However, treatment modalities and intensity were different for old and unfit patients. Physicians answered that they would treat old fit patients as their younger counterparts but would reduce treatment intensity for old unfit patients. However, even if they were willing to adapt their treatment strategy based on frailty status, most of them do not use the tools that would allow distinguishing “fit” and “unfit” older patients, leaving room for improving accurate geriatric evaluation. Full article
(This article belongs to the Special Issue Therapies in Cervical Cancer)
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