Management of Early Stage Cervical Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (15 June 2022) | Viewed by 37602

Special Issue Editors

Gynecologic Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
Interests: cervical cancer; minimally invasive surgery; fertility sparing treatments; translational medicine; sentinel lymph node concept; gynecological cancers
Special Issues, Collections and Topics in MDPI journals
Gynecologic Oncology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
Interests: cervical cancer; minimally invasive surgery; translational medicine; sentinel lymph node; gynecological cancers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cervical carcinoma is a common gynecological malignancy, still representing a challenge for oncologic gynecologists around the world.

A proper and accurate preoperative staging of early-stage disease, obtained through advancements of diagnostic procedures (US, MRI, PET scan), allows personalized treatments. Modulation of surgical radicality, fertility sparing therapies, sentinel node technique, concept of ovarian preservation, introduction of translational medicine, and molecular investigations are the cornerstones of cervical cancer treatment that, in recent years, have become increasingly tailored. In this context, management of cervical cancer requires a multidisciplinary approach involving oncologic gynecologists, medical oncologists, radiologists, radiotherapists, and pathologists. The aim of this Special Issue is to focus on new evidence regarding diagnosis and treatment of early-stage cervical cancer, which could lead to an improvement in clinical practice or could set up new research frontiers in the management of this disease.

Dr. Valerio Gallotta
Dr. Luigi Pedone Anchora
Guest Editors

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Keywords

  • cervical cancer
  • fertility sparing
  • sentinel lymph node
  • radical surgery
  • diagnosis and staging
  • prognostic characterization
  • personalized treatment
  • adjuvant therapy
  • molecular investigations
  • translational medicine

Published Papers (11 papers)

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Editorial

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4 pages, 203 KiB  
Editorial
Special Issue: “Management of Early Stage Cervical Cancer”
Cancers 2023, 15(8), 2343; https://doi.org/10.3390/cancers15082343 - 18 Apr 2023
Viewed by 865
Abstract
Cervical carcinoma is a common gynecological malignancy that remains a challenge for oncologic gynecologists around the world [...] Full article
(This article belongs to the Special Issue Management of Early Stage Cervical Cancer)

Research

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9 pages, 1399 KiB  
Communication
Ultrastaging of the Parametrium in Cervical Cancer: A Clinicopathological Study
Cancers 2023, 15(4), 1099; https://doi.org/10.3390/cancers15041099 - 09 Feb 2023
Cited by 2 | Viewed by 1383
Abstract
Occult parametrial involvement in apparent early-stage cervical cancer might be overlooked with standard pathologic assessment. The primary endpoint of the present study was to assess the rate of positive parametrial lymph nodes and of microscopic continuous or discontinuous parametrial involvement. This is a [...] Read more.
Occult parametrial involvement in apparent early-stage cervical cancer might be overlooked with standard pathologic assessment. The primary endpoint of the present study was to assess the rate of positive parametrial lymph nodes and of microscopic continuous or discontinuous parametrial involvement. This is a retrospective, single-center, observational study including patients with FIGO 2018 stage IA1–IIA1 and IIIC1p in whom bilateral sentinel lymph node (SLN) detection and ultrastaging of SLN were performed according to institutional protocol, with surgery as primary treatment performed between May 2017 and February 2021, as well as type B2/C1/C2 (Querleu–Morrow) radical hysterectomy and usual histology (squamous cell, adenocarcinoma and adenosquamous carcinoma). Thirty-one patients were included in the study period. Six (18.7%) patients had metastatic lymph nodes, of whom four had only SLN metastasis (two cases of ITC, one case of micrometastasis and one case of macrometastasis). We found a macroscopic deposit of cancer cells in the parametrial lymph node of one patient (3.1%). There was a positive statistical correlation between the incidence of parametrial lymph node involvement and the metastatic pelvic lymph nodes (p = 0.038). When performed per patient, the sensitivity, negative predictive value and accuracy of parametrial lymph node involvement in predicting pelvic lymph node metastasis were 16.7%, 83.3% and 83.9%, respectively. Ultrastaging of parametrial tissue did not identify any occult continuous or discontinuous parametrial metastasis. In conclusion, the incidence of lymph node parametrial involvement in a retrospective series of early-stage cervical cancer was 3.1% of all included patients. Lymph node involvement of the parametrium was associated with lymph node metastasis. The sensitivity of parametrial lymph node involvement to predict pelvic lymph node metastasis was low. The lack of parametrial involvement revealed by parametrial ultrastaging could be related to the number of patients with tumors with a pathologic diameter < 2 cm (54.8%). Further prospective studies are needed to analyze the role of parametrial ultrastaging in early-stage cervical cancer and to assess whether it can be considered the “sentinel” of the sentinel lymph node. Full article
(This article belongs to the Special Issue Management of Early Stage Cervical Cancer)
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13 pages, 1079 KiB  
Article
Trends in Pregnancy-Associated Cervical Cancer in Japan between 2012 and 2017: A Multicenter Survey
Cancers 2022, 14(13), 3072; https://doi.org/10.3390/cancers14133072 - 23 Jun 2022
Cited by 1 | Viewed by 2086
Abstract
Large-scale data on maternal and neonatal outcomes of pregnancy-associated cervical cancer in Japan are scarce, and treatment strategies have not been established. This multicenter retrospective observational study investigated clinical features and trends in pregnancy-associated cervical cancer treatments at 523 hospitals in Japan. We [...] Read more.
Large-scale data on maternal and neonatal outcomes of pregnancy-associated cervical cancer in Japan are scarce, and treatment strategies have not been established. This multicenter retrospective observational study investigated clinical features and trends in pregnancy-associated cervical cancer treatments at 523 hospitals in Japan. We included cervical cancer cases that were histologically diagnosed (between 1 January 2012, and 31 December 2017), and their clinical information was retrospectively collected. Of 40 patients diagnosed with pregnancy-associated cervical cancer at ≥22 gestational weeks, 34 (85.0%) were carefully followed until delivery without intervention. Of 163 diagnosed at <22 gestational weeks, 111 continued and 52 terminated their pregnancy. Ninety patients with stage IB1 disease had various treatment options, including termination of pregnancy. The 59 stage IB1 patients who continued their pregnancy were categorized by the primary treatment into strict follow-up, conization, trachelectomy, and neoadjuvant chemotherapy groups, with no significant differences in progression-free or overall survival. The birth weight percentile at delivery was smaller in the neoadjuvant chemotherapy group than in the strict follow-up group (p = 0.029). Full-term delivery rate was relatively higher in the trachelectomy group (35%) than in the other groups. Treatment decisions for pregnancy-associated cervical cancer are needed after estimating the stage, considering both maternal and fetal benefits. Full article
(This article belongs to the Special Issue Management of Early Stage Cervical Cancer)
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10 pages, 1627 KiB  
Article
Utility of 3T MRI in Women with IB1 Cervical Cancer in Determining the Necessity of Less Invasive Surgery
Cancers 2022, 14(1), 224; https://doi.org/10.3390/cancers14010224 - 04 Jan 2022
Cited by 3 | Viewed by 1738
Abstract
Purpose: Cervical cancer that is invisible on magnetic resonance imaging (MRI) may suggest lower tumor burden than physical examination. Recently, 3 tesla (3T) MRI has been widely used prior to surgery because of its higher resolution than 1.5T MRI. The aim was to [...] Read more.
Purpose: Cervical cancer that is invisible on magnetic resonance imaging (MRI) may suggest lower tumor burden than physical examination. Recently, 3 tesla (3T) MRI has been widely used prior to surgery because of its higher resolution than 1.5T MRI. The aim was to retrospectively evaluate the utility of 3T MRI in women with early cervical cancer in determining the necessity of less invasive surgery. Materials and methods: Between January 2010 and December 2015, a total of 342 women with FIGO stage IB1 cervical cancer underwent 3T MRI prior to radical hysterectomy, vaginectomy, and lymph node dissection. These patients were classified into cancer-invisible (n = 105) and cancer-visible (n = 237) groups based on the 3T MRI findings. These groups were compared regarding pathologic parameters and long-term survival rates. Results: The cancer sizes of the cancer-invisible versus cancer-visible groups were 11.5 ± 12.2 mm versus 30.1 ± 16.2 mm, respectively (p < 0.001). The depths of stromal invasion in these groups were 20.5 ± 23.6% versus 63.5 ± 31.2%, respectively (p < 0.001). Parametrial invasion was 0% (0/105) in the cancer-invisible group and 21.5% (51/237) in the cancer-visible group (odds ratio = 58.3, p < 0.001). Lymph node metastasis and lymphovascular space invasion were 5.9% (6/105) versus 26.6% (63/237) (5.8, p < 0.001) and 11.7% (12/105) versus 40.1% (95/237) (5.1, p < 0.001), respectively. Recurrence-free and overall 5-year survival rates were 99.0% (104/105) versus 76.8% (182/237) (p < 0.001) and 98.1% (103/105) versus 87.8% (208/237) (p = 0.003), respectively. Conclusions: 3T MRI can play a great role in determining the necessity of parametrectomy in women with IB1 cervical cancer. Therefore, invisible cervical cancer on 3T MRI will be a good indicator for less invasive surgery. Full article
(This article belongs to the Special Issue Management of Early Stage Cervical Cancer)
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12 pages, 1415 KiB  
Article
Oncologic Outcomes of Laparoscopic Radical Hysterectomy Using the No-Look No-Touch Technique for Early Stage Cervical Cancer: A Propensity Score-Adjusted Analysis
Cancers 2021, 13(23), 6097; https://doi.org/10.3390/cancers13236097 - 03 Dec 2021
Cited by 15 | Viewed by 2776
Abstract
We evaluated oncologic outcomes of laparoscopic radical hysterectomy using the no-look no-touch technique (NLNT). We analyzed patients with early stage (IA2, IB1, and IIA1, FIGO2008) cervical cancer treated between December 2014 and December 2019. The primary endpoint was disease-free survival (DFS). We compared [...] Read more.
We evaluated oncologic outcomes of laparoscopic radical hysterectomy using the no-look no-touch technique (NLNT). We analyzed patients with early stage (IA2, IB1, and IIA1, FIGO2008) cervical cancer treated between December 2014 and December 2019. The primary endpoint was disease-free survival (DFS). We compared the outcomes of the abdominal radical hysterectomy (ARH) and NLNT groups using a Cox model with inverse probability of treatment weighting (IPTW), according to propensity scores. We also evaluated NLNT’s non-inferiority to ARH using an evaluation of heterogeneity between the results of the Laparoscopic Approach to Cervical Cancer (LACC) trial and our study. ARH and NLNT were performed in 118 and 113 patients, respectively. The median follow-up duration was 3.2 years. After IPTW adjustment, the 3-year DFS rates (NLNT 92.4%; ARH 94.0%) and overall survival rates did not differ significantly between the groups. Furthermore, the 3-year DFS rates for patients with tumor sizes ≥ 2 cm in the NLNT (85.0%) and ARH (90.3%) groups did not differ significantly. No significant heterogeneity was observed between the LACC trial and our study (I2 = 60.5%, p = 0.111), although there was a trend toward a lower hazard ratio in our study. Laparoscopic radical hysterectomy using NLNT provides a favorable prognosis for early stage cervical cancer. Full article
(This article belongs to the Special Issue Management of Early Stage Cervical Cancer)
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14 pages, 321 KiB  
Article
Can Conization Specimens Predict Sentinel Lymph Node Status in Early-Stage Cervical Cancer? A SENTICOL Group Study
Cancers 2021, 13(21), 5423; https://doi.org/10.3390/cancers13215423 - 29 Oct 2021
Cited by 4 | Viewed by 1573
Abstract
Background: The prognosis of patients with cervical cancer is significantly worsened in case of lymph node involvement. The goal of this study was to determine whether pathologic features in conization specimens can predict the sentinel lymph node (SLN) status in early-stage cervical cancer. [...] Read more.
Background: The prognosis of patients with cervical cancer is significantly worsened in case of lymph node involvement. The goal of this study was to determine whether pathologic features in conization specimens can predict the sentinel lymph node (SLN) status in early-stage cervical cancer. Methods: An ancillary analysis of two prospective multicentric database on SLN biopsy for cervical cancer (SENTICOL I and II) was carried out. Patients with IA to IB2 2018 FIGO stage, who underwent preoperative conization before SLN biopsy were included. Results: Between January 2005 and July 2012, 161 patients from 25 French centers fulfilled the inclusion criteria. Macrometastases, micrometastases and Isolated tumor cells (ITCs) were found in 4 (2.5%), 6 (3.7%) and 5 (3.1%) patients respectively. Compared to negative SLN patients, patients with micrometastatic and macrometastatic SLN were more likely to have lymphovascular space invasion (LVSI) (60% vs. 29.5%, p = 0.04) and deep stromal invasion (DSI) ≥ 10 mm (50% vs. 17.8%, p = 0.04). Among the 93 patients with DSI < 10 mm and absence of LVSI on conization specimens, three patients (3.2%) had ITCs and only one (1.1%) had micrometastases. Conclusions: Patients with DSI < 10 mm and no LVSI in conization specimens had lower risk of micro- and macrometastatic SLN. In this subpopulation, full node dissection may be questionable in case of SLN unilateral detection. Full article
(This article belongs to the Special Issue Management of Early Stage Cervical Cancer)
12 pages, 2135 KiB  
Article
Transcription Factor Homeobox D9 Drives the Malignant Phenotype of HPV18-Positive Cervical Cancer Cells via Binding to the Viral Early Promoter
Cancers 2021, 13(18), 4613; https://doi.org/10.3390/cancers13184613 - 15 Sep 2021
Cited by 4 | Viewed by 2621
Abstract
Persistent infections with two types of human papillomaviruses (HPV), HPV16 and HPV18, are the most common cause of cervical cancer (CC). Two viral early genes, E6 and E7, are associated with tumor development, and expressions of E6 and E7 are primarily regulated [...] Read more.
Persistent infections with two types of human papillomaviruses (HPV), HPV16 and HPV18, are the most common cause of cervical cancer (CC). Two viral early genes, E6 and E7, are associated with tumor development, and expressions of E6 and E7 are primarily regulated by a single viral promoter: P97 in HPV16 and P105 in HPV18. We previously demonstrated that the homeobox D9 (HOXD9) transcription factor is responsible for the malignancy of HPV16-positive CC cell lines via binding to the P97 promoter. Here, we investigated whether HOXD9 is also involved in the regulation of the P105 promoter using two HPV18-positive CC cell lines, SKG-I and HeLa. Following the HOXD9 knockdown, cell viability was significantly reduced, and E6 expression was suppressed and was accompanied by increased protein levels of P53, while mRNA levels of TP53 did not change. E7 expression was also downregulated and, while mRNA levels of RB1 and E2F were unchanged, mRNA levels of E2F-target genes, MCM2 and PCNA, were decreased, which indicates that the HOXD9 knockdown downregulates E7 expression, thus leading to an inactivation of E2F and the cell-cycle arrest. Chromatin immunoprecipitation and promoter reporter assays confirmed that HOXD9 is directly associated with the P105 promoter. Collectively, our results reveal that HOXD9 drives the HPV18 early promoter activity to promote proliferation and immortalization of the CC cells. Full article
(This article belongs to the Special Issue Management of Early Stage Cervical Cancer)
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Review

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19 pages, 562 KiB  
Review
Neoadjuvant Chemotherapy Prior Fertility-Sparing Surgery in Women with FIGO 2018 Stage IB2 Cervical Cancer: A Systematic Review
Cancers 2022, 14(3), 797; https://doi.org/10.3390/cancers14030797 - 04 Feb 2022
Cited by 6 | Viewed by 2023
Abstract
Nowadays, the optimal management of patients with cervical cancers measuring 2–4 cm desiring to maintain fertility is still uncertain. In this systematic review, we assessed the reliability of neoadjuvant chemotherapy (NACT) prior to fertility-sparing (FS) surgery in International Federation of Gynecology and Obstetrics [...] Read more.
Nowadays, the optimal management of patients with cervical cancers measuring 2–4 cm desiring to maintain fertility is still uncertain. In this systematic review, we assessed the reliability of neoadjuvant chemotherapy (NACT) prior to fertility-sparing (FS) surgery in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB2 cervical cancer, in terms of pathologic response, oncological and obstetric outcomes. The review of the literature was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data, using MEDLINE and PubMed, were searched for from 1 January 2005 up to 1 December 2020. We identified 20 articles and 114 women with IB2 disease, possible candidates for NACT prior to FS surgery. However, uterine conservation was achieved only in 76.7% of them. Patients reached optimal pathological response to NACT in 60.9% of cases and a TIP (cisplatin, ifosfamide and paclitaxel) regime was related to the best response. Suboptimal response to NACT appeared to be an independent negative prognostic factor. Up to 9.2% of patients recurred with a median 7.4-months DFS, and 4.6% of patients died of disease. Fifty percent of women tried to conceive after treatment and NACT prior to conization appeared to be the most promising alternative to upfront radical trachelectomy in terms of obstetric outcomes. In conclusion, NACT prior to FS surgery is an option, but the literature about this issue is still weak and FS should be carefully discussed with patients. Full article
(This article belongs to the Special Issue Management of Early Stage Cervical Cancer)
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17 pages, 1005 KiB  
Review
Management of Early-Stage Cervical Cancer: A Literature Review
Cancers 2022, 14(3), 575; https://doi.org/10.3390/cancers14030575 - 24 Jan 2022
Cited by 28 | Viewed by 8354
Abstract
Cervical cancer (CC) remains a public health issue worldwide despite preventive measures. Surgical treatment in the early-stage CC has evolved during the last decades. Our aim was to review the advances in the literature and summarize the ongoing studies on this topic. To [...] Read more.
Cervical cancer (CC) remains a public health issue worldwide despite preventive measures. Surgical treatment in the early-stage CC has evolved during the last decades. Our aim was to review the advances in the literature and summarize the ongoing studies on this topic. To this end, we conducted a literature review through PubMed focusing on English-language articles on the surgical management of early-stage CC. The emergent topics considered here are the FIGO 2018 staging system update, conservative management with less radical procedures for selected patients, lymph node staging, fertility preservation, preferred surgical approach, management of tumors up to 2 cm, and prognosis. In terms of updating FIGO, we highlight the inclusion of lymph node status on staging and the possibility of imaging. Regarding the preferred surgical approach, we emphasize the LACC trial impact worldwide in favor of open surgery; however, we discuss the controversial application of this for tumors < 2 cm. In summary, all topics show a tendency to provide patients with tailored treatment that avoids morbidity while maintaining oncologic safety, which is already possible in high-income countries. We believe that efforts should focus on making this a reality for low-income countries as well. Full article
(This article belongs to the Special Issue Management of Early Stage Cervical Cancer)
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14 pages, 2878 KiB  
Review
Useful MRI Findings for Minimally Invasive Surgery for Early Cervical Cancer
Cancers 2021, 13(16), 4078; https://doi.org/10.3390/cancers13164078 - 13 Aug 2021
Cited by 7 | Viewed by 5242
Abstract
According to the recent International Federation of Gynecology and Obstetrics (FIGO) staging system, Stage III cervical cancer indicates pelvic or paraaortic lymph node metastasis. Accordingly, the new FIGO stage accepts imaging modalities, such as MRI, as part of the FIGO 2018 updated staging. [...] Read more.
According to the recent International Federation of Gynecology and Obstetrics (FIGO) staging system, Stage III cervical cancer indicates pelvic or paraaortic lymph node metastasis. Accordingly, the new FIGO stage accepts imaging modalities, such as MRI, as part of the FIGO 2018 updated staging. Magnetic resonance imaging (MRI) is the best imaging modality to estimate the size or volume of uterine cancer because of its excellent soft tissue contrast. As a result, MRI is being used increasingly to determine treatment options and follow-up for cervical cancer patients. Increasing availability of cancer screening and vaccination have improved early detection of cervical cancer. However, the incidence of early cervical cancers has increased compared to that of advanced cervical cancer. A few studies have investigated if MRI findings are useful in management of early cervical cancer. MRI can precisely predict tumor burden, allowing conization, trachelectomy, and simple hysterectomy to be considered as minimally invasive treatment options for early cervical cancer. This imaging modality also can be used to determine whether there is recurrent cancer following minimally invasive treatments. The purpose of this review is to highlight useful MRI features for managing women with early cervical cancer. Full article
(This article belongs to the Special Issue Management of Early Stage Cervical Cancer)
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Other

13 pages, 6234 KiB  
Perspective
A New Anatomic and Staging-Oriented Classification of Radical Hysterectomy
Cancers 2021, 13(13), 3326; https://doi.org/10.3390/cancers13133326 - 02 Jul 2021
Cited by 9 | Viewed by 7325
Abstract
The current understanding of radical hysterectomy more is centered on the uterus and little is being discussed about the resection of the vaginal cuff and the paracolpium as an essential part of this procedure. This is because that the current classifications of radical [...] Read more.
The current understanding of radical hysterectomy more is centered on the uterus and little is being discussed about the resection of the vaginal cuff and the paracolpium as an essential part of this procedure. This is because that the current classifications of radical hysterectomy are based only on the lateral extent of resection. This way is easier to be understood but does not reflect the anatomical and surgical conception of radical hysterectomy and the three-dimensional ways of tumour spreading, neither meet the need of adjusting the radicality according to the different stages of FIGO classification, which depends—at least in the early stages—on the tumour volume and the infiltration in the vagina (but not on the directly spread in the parametrium). The new classification presented in this paper does not base anymore on the lateral extent of resection only but too on the depth of resection in the small pelvic and the extent of the resected vaginal vault without or with its three-dimensional paracolpium. This classification takes into account the tumour size, stage, localization and infiltration in the vaginal vault and may offer the optimal tool to adjust and tailor the surgery according to these important variables. Full article
(This article belongs to the Special Issue Management of Early Stage Cervical Cancer)
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