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13 pages, 1358 KiB

Open AccessArticle

HPV16 Load Is a Potential Biomarker to Predict Risk of High-Grade Cervical Lesions in High-Risk HPV-Infected Women: A Large Longitudinal French Hospital-Based Cohort Study

by Antoine Baumann, Julie Henriques, Zohair Selmani, Aurélia Meurisse, Quentin Lepiller, Dewi Vernerey, Séverine Valmary-Degano, Sophie Paget-Bailly, Didier Riethmuller, Rajeev Ramanah, Christiane Mougin and Jean-Luc Prétet

Cancers 2021, 13(16), 4149; https://doi.org/10.3390/cancers13164149 - 18 Aug 2021

Cited by 9 | Viewed by 1991

Abstract

High-risk HPV (hrHPV) testing has been implemented as a primary screening tool for cervical cancer in numerous countries. However, there is still a need for relevant triage strategies to manage hrHPV positive women to avoid excessive referral to colposcopy. The objective of this [...] Read more.

High-risk HPV (hrHPV) testing has been implemented as a primary screening tool for cervical cancer in numerous countries. However, there is still a need for relevant triage strategies to manage hrHPV positive women to avoid excessive referral to colposcopy. The objective of this study was to assess, in women infected by hrHPV and presenting no or mild cytological abnormalities, HPV16 and HPV18 viral loads to predict the development of cervical high-grade lesion. Among 2102 women positive for hrHPV, 885 had no lesion or mild cytological abnormalities at baseline and had at least one follow-up (FU) visit. HPV16 and HPV18 prevalence was 25.9% and 8.4%, respectively. Of those women, 15% developed a high-grade lesion during the FU. An HPV16 viral load cut-off set at 3.2 log₁₀GE/10³ cells permitted to identify a subgroup of women at high risk of developing high-grade cervical lesion (HR = 2.67; 95% CI 1.80–3.97; p ≤ 0.0001). No specific HPV18 viral load threshold could have been defined in regard to the present study. In multivariate analysis, HPV16 load (absence/log₁₀GE/10³ cells < 3.2 vs. ≥3.2), RLU/PC 239 (1–100 pg/mL vs. >100 pg/mL) and cytology (normal vs abnormal) were independently associated with a significant increased risk of high-grade lesion development and were used to construct the prognostic score. In conclusion, HPV16 load is a relevant biomarker to identify women at high risk for developing cervical precancerous lesions. Full article

(This article belongs to the Special Issue Cervical Carcinoma)

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16 pages, 7727 KiB

Open AccessArticle

Aptamer-Functionalized Gold Nanoparticles for Drug Delivery to Gynecological Carcinoma Cells

by Jessica Lopes-Nunes, Ana S. Agonia, Tiago Rosado, Eugénia Gallardo, Rita Palmeira-de-Oliveira, Ana Palmeira-de-Oliveira, José Martinez-de-Oliveira, José Fonseca-Moutinho, Maria Paula Cabral Campello, Artur Paiva, António Paulo, Alexa Vulgamott, Andrew D. Ellignton, Paula A. Oliveira and Carla Cruz

Cancers 2021, 13(16), 4038; https://doi.org/10.3390/cancers13164038 - 11 Aug 2021

Cited by 19 | Viewed by 4142

Abstract

Cervical cancer is one of the most common cancers and is one of the major cause of deaths in women, especially in underdeveloped countries. The patients are usually treated with surgery, radiotherapy, and chemotherapy. However, these treatments can cause several side effects and [...] Read more.

Cervical cancer is one of the most common cancers and is one of the major cause of deaths in women, especially in underdeveloped countries. The patients are usually treated with surgery, radiotherapy, and chemotherapy. However, these treatments can cause several side effects and may lead to infertility. Another concerning gynecologic cancer is endometrial cancer, in which a high number of patients present a poor prognosis with low survival rates. AS1411, a DNA aptamer, increases anticancer therapeutic selectivity, and through its conjugation with gold nanoparticles (AS1411-AuNPs) it is possible to improve the anticancer effects. Therefore, AS1411-AuNPs are potential drug carriers for selectively delivering therapeutic drugs to cervical cancer. In this work, we used AS1411-AuNPs as a carrier for an acridine orange derivative (C₈) or Imiquimod (IQ). The AS1411 aptamer was covalently bound to AuNPs, and each drug was associated via supramolecular assembly. The final nanoparticles presented suitable properties for pharmaceutical applications, such as small size, negative charge, and favorable drug release properties. Cellular uptake was characterized by confocal microscopy and flow cytometry, and effects on cellular viability were determined by MTT assay. The nanoparticles were then incorporated into a gel formulation of polyethylene glycol, suitable for topical application in the female genital tract. This gel showed promising tissue retention properties in Franz cells studies in the porcine vaginal epithelia. These findings suggest that the tested nanoparticles are promising drug carriers for cervical cancer therapy. Full article

(This article belongs to the Special Issue Cervical Carcinoma)

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12 pages, 1252 KiB

Open AccessArticle

Human Papillomavirus Same Genotype Persistence and Risk of Cervical Intraepithelial Neoplasia2+ Recurrence

by Anna Daniela Iacobone, Davide Radice, Maria Teresa Sandri, Eleonora Petra Preti, Maria Elena Guerrieri, Ailyn Mariela Vidal Urbinati, Ida Pino, Dorella Franchi, Rita Passerini and Fabio Bottari

Cancers 2021, 13(15), 3664; https://doi.org/10.3390/cancers13153664 - 21 Jul 2021

Cited by 5 | Viewed by 2115

Abstract

To evaluate the significance of HPV persistence as a predictor for the development of CIN2+ recurrence and the impact of multiple genotypes and of HPV 16/18 on recurrence risk. A prospective cohort observational study was carried out at the European Institute of Oncology, [...] Read more.

To evaluate the significance of HPV persistence as a predictor for the development of CIN2+ recurrence and the impact of multiple genotypes and of HPV 16/18 on recurrence risk. A prospective cohort observational study was carried out at the European Institute of Oncology, Milan, Italy, from December 2006 to December 2014. A total of 408 women surgically treated by excisional procedure for pre-neoplastic and neoplastic cervical lesions were enrolled. HPV test was performed at baseline and at first follow-up visit planned at 6 ± 3 months after treatment. Two-year cumulative incidences for relapse were estimated and compared by the Gray’s test. Overall, 96 (23.5%) patients were persistent for at least one genotype at three to nine months from baseline and 21 (5.1%) patients relapsed. The two-year cumulative relapse incidence was higher in HPV persistent patients compared to not-persistent (CIF = 27.6%, 95% CI: 16.2–40.2% versus CIF = 1.7%, 95% CI: 0.3–5.8%, p < 0.001), in women with persistent multiple infections (CIF = 27.2%, 95% CI: 7.3–52.3%, p < 0.001), and with the persistence of at least one genotype between 16 and 18, irrespective of the presence of other HR genotypes (CIF = 32.7%, 95% CI: 17.9–48.3%, p < 0.001), but not significantly different from women positive for single infections or any other HR genotype, but not for 16 and 18. The risk of CIN2+ recurrence should not be underestimated when same HPV genotype infection persists after treatment. Full article

(This article belongs to the Special Issue Cervical Carcinoma)

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12 pages, 1190 KiB

Open AccessArticle

Oncological Results of Laparoscopically Assisted Radical Vaginal Hysterectomy in Early-Stage Cervical Cancer: Should We Really Abandon Minimally Invasive Surgery?

by Aureli Torné, Jaume Pahisa, Jaume Ordi, Pere Fusté, Berta Díaz-Feijóo, Ariel Glickman, Pilar Paredes, Angels Rovirosa, Lydia Gaba, Adela Saco, Carlos Nicolau, Núria Carreras, Núria Agustí, Sergi Vidal-Sicart, Blanca Gil-Ibáñez and Marta del Pino

Cancers 2021, 13(4), 846; https://doi.org/10.3390/cancers13040846 - 17 Feb 2021

Cited by 8 | Viewed by 3913

Abstract

Background: Recent evidence indicates that some minimally invasive surgery approaches, such as laparoscopic and robotic-assisted radical hysterectomy, offer lower survival rates to patients with early-stage cervical cancer than open radical hysterectomy. We evaluated the oncological results of a different minimally invasive surgery approach, [...] Read more.

Background: Recent evidence indicates that some minimally invasive surgery approaches, such as laparoscopic and robotic-assisted radical hysterectomy, offer lower survival rates to patients with early-stage cervical cancer than open radical hysterectomy. We evaluated the oncological results of a different minimally invasive surgery approach, that of laparoscopically assisted radical vaginal hysterectomy (LARVH) in this setting. Methods: From January 2001 to December 2018, patients with early-stage cervical cancer were treated by LARVH. Colpotomy and initial closure of the vagina were performed following the Schauta operation, avoiding manipulation of the tumor. Laparoscopic sentinel lymph node (SLN) biopsy was performed in all cases. Women treated between 2001 and 2011 also underwent pelvic lymphadenectomy. Results: There were 115 patients included. Intraoperative complications occurred in nine patients (7.8%). After a median follow-up of 87.8 months (range 1–216), seven women (6%) presented recurrence. Four women died (mortality rate 3.4%). The 3- and 4.5-year disease-free survival rates were 96.7% and 93.5%, respectively, and the overall survival was 97.8% and 94.8%, respectively. Conclusion: LARVH offers excellent disease-free and overall survival in women with early-stage cervical cancer and can be considered as an adequate minimally invasive surgery alternative to open radical hysterectomy. Full article

(This article belongs to the Special Issue Cervical Carcinoma)

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12 pages, 1154 KiB

Open AccessArticle

Results of a Phase I-II Study on Laser Therapy for Vaginal Side Effects after Radiotherapy for Cancer of Uterine Cervix or Endometrium

by Anna Myriam Perrone, Marco Tesei, Martina Ferioli, Francesca De Terlizzi, Anna Nunzia Della Gatta, Safia Boussedra, Giulia Dondi, Andrea Galuppi, Alessio Giuseppe Morganti and Pierandrea De Iaco

Cancers 2020, 12(6), 1639; https://doi.org/10.3390/cancers12061639 - 21 Jun 2020

Cited by 18 | Viewed by 3652

Abstract

Women who have previously received radiotherapy (RT) for gynecologic cancer often suffer from vaginal fibrosis and stenosis. The success of “non-ablative” laser therapy for postmenopausal vaginal atrophy has led to the idea of testing the laser in patients submitted to RT. In this [...] Read more.

Women who have previously received radiotherapy (RT) for gynecologic cancer often suffer from vaginal fibrosis and stenosis. The success of “non-ablative” laser therapy for postmenopausal vaginal atrophy has led to the idea of testing the laser in patients submitted to RT. In this prospective observational study, we selected patients who underwent pelvic RT followed by vaginal laser treatment. We scheduled three treatment sessions (at T0–T1–T2) and three controls (at T1–T2–T3) one month apart. The follow-up (at T4) was carried out six months after the last treatment. Vaginal Health Index (VHI) and vaginal length were evaluated. Sexual function was assessed through Female Sexual Function Index (FSFI). Overall, 43 patients with severe vaginal shortening, atrophy and stenosis was enrolled and treated with intravaginal non-ablative CO₂ laser. We observed a progressive increase in vaginal length of 9% (p = 0.03) at T2 and 28% (p < 0.0001) at T3; effects were maintained at T4 (p < 0.0001). After the first application VHI showed a significant improvement of 57% at T3 (p < 0.0001). The results were maintained at T4 (p < 0.0001). No changes were found in FSFI. All procedures were well tolerated. In conclusion, laser therapy improved vaginal length and VHI in women undergoing pelvic RT; prospective studies are needed. Full article

(This article belongs to the Special Issue Cervical Carcinoma)

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12 pages, 1124 KiB

Open AccessArticle

Should the Number of Metastatic Pelvic Lymph Nodes Be Integrated into the 2018 Figo Staging Classification of Early Stage Cervical Cancer?

by Luigi Pedone Anchora, Vittoria Carbone, Valerio Gallotta, Francesco Fanfani, Francesco Cosentino, Luigi Carlo Turco, Camilla Fedele, Nicolò Bizzarri, Giovanni Scambia and Gabriella Ferrandina

Cancers 2020, 12(6), 1552; https://doi.org/10.3390/cancers12061552 (registering DOI) - 12 Jun 2020

Cited by 20 | Viewed by 2735

Abstract

Introduction: Lymph node status has become part of the new staging system for cervical cancer (CC). It has been shown that patients staged as IIIC1 had heterogeneous prognoses and, in some cases, experienced better outcomes than patients with lower stages. We evaluated the [...] Read more.

Introduction: Lymph node status has become part of the new staging system for cervical cancer (CC). It has been shown that patients staged as IIIC1 had heterogeneous prognoses and, in some cases, experienced better outcomes than patients with lower stages. We evaluated the impact of the number of metastatic pelvic lymph nodes (MPLNs) among patients with stage IIIC1 cervical cancer. Methods: Survival analyses were conducted in order to identify the best cut-off prognostic value relative to the number of MPLNs. Disease free survival (DFS) was considered the main outcome. Results: 541 patients were included in the study. Eighty-nine patients were of stage IIIC1. The best prognostic cut-off value of the number of MPLNs was 2. Patients with >2 MPLNs (n > 2 group) had worse DFS compared with those having <2 (N1-2 group) (5 yr DFS: 54.7% vs. 78.1%, p value = 0.006). Multivariate analyses demonstrated that the extent of MPLNs had little impact on DFS and that replacement of IIIC1 staging with N1-2 and n > 2 grouping provided a better, statistically significant model (p value = 0.006). Discussion: Using a cut-off value of 2, the number of MPLNs could better predict prognostic outcomes within stage IIIC1 cervical cancer and have potential implications for therapeutic decision-making in the treatment of patients with stage IIIC1 CC. Full article

(This article belongs to the Special Issue Cervical Carcinoma)

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Review

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19 pages, 339 KiB

Open AccessReview

Liquid Biopsy in Cervical Cancer: Hopes and Pitfalls

by Paola Cafforio, Raffaele Palmirotta, Domenica Lovero, Ettore Cicinelli, Gennaro Cormio, Erica Silvestris, Camillo Porta and Stella D’Oronzo

Cancers 2021, 13(16), 3968; https://doi.org/10.3390/cancers13163968 - 5 Aug 2021

Cited by 11 | Viewed by 3746

Abstract

Cervical cancer (CC) is the fourth most common cancer in women worldwide, with about 90% of cancer-related deaths occurring in developing countries. The geographical influence on disease evolution reflects differences in the prevalence of human papilloma virus (HPV) infection, which is the main [...] Read more.

Cervical cancer (CC) is the fourth most common cancer in women worldwide, with about 90% of cancer-related deaths occurring in developing countries. The geographical influence on disease evolution reflects differences in the prevalence of human papilloma virus (HPV) infection, which is the main cause of CC, as well as in the access and quality of services for CC prevention and diagnosis. At present, the most diffused screening and diagnostic tools for CC are Papanicolaou test and the more sensitive HPV-DNA test, even if both methods require gynecological practices whose acceptance relies on the woman’s cultural and religious background. An alternative (or complimentary) tool for CC screening, diagnosis, and follow-up might be represented by liquid biopsy. Here, we summarize the main methodologies developed in this context, including circulating tumor cell detection and isolation, cell tumor DNA sequencing, coding and non-coding RNA detection, and exosomal miRNA identification. Moreover, the pros and cons of each method are discussed, and their potential applications in diagnosis and prognosis of CC, as well as their role in treatment monitoring, are explored. In conclusion, it is evident that despite many advances obtained in this field, further effort is needed to validate and standardize the proposed methodologies before any clinical use. Full article

(This article belongs to the Special Issue Cervical Carcinoma)

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20 pages, 271 KiB

Open AccessReview

Pharmacological Treatment of Patients with Metastatic, Recurrent or Persistent Cervical Cancer Not Amenable by Surgery or Radiotherapy: State of Art and Perspectives of Clinical Research

by Angiolo Gadducci and Stefania Cosio

Cancers 2020, 12(9), 2678; https://doi.org/10.3390/cancers12092678 - 19 Sep 2020

Cited by 9 | Viewed by 3244

Abstract

Cervical cancer patients with distant or loco-regional recurrences not amenable by surgery or radiotherapy have limited treatment options, and their 5-year overall survival (OS) rates range from 5% to 16%. The purpose of this paper is to assess the results obtained with chemotherapy [...] Read more.

Cervical cancer patients with distant or loco-regional recurrences not amenable by surgery or radiotherapy have limited treatment options, and their 5-year overall survival (OS) rates range from 5% to 16%. The purpose of this paper is to assess the results obtained with chemotherapy and biological agents in this clinical setting. Several phase II trials of different cisplatin (CDDP)-based doublets and a phase III randomized trial showing a trend in response rate, progression-free survival, and OS in favor of CDDP + paclitaxel (PTX) compared with other CDDP-based doublets have been reviewed. The factors predictive of response to chemotherapy as well as the benefits and risks of the addition of bevacizumab to CDDP + PTX have been analyzed. The FDA has recently approved pembrolizumab for patients with recurrent or metastatic cervical cancer in progression on or after chemotherapy whose tumors were PD-L1 positive. Interesting perspectives of clinical research are represented by the use of immune checkpoint inhibitors alone or in addition to chemotherapy, whereas PARP inhibitors and PI3K inhibitors are still at the basic research phase, but promising. Full article

(This article belongs to the Special Issue Cervical Carcinoma)

33 pages, 2353 KiB

Open AccessReview

Targeted Gene Delivery Therapies for Cervical Cancer

by Ángela Áyen, Yaiza Jiménez Martínez and Houria Boulaiz

Cancers 2020, 12(5), 1301; https://doi.org/10.3390/cancers12051301 - 21 May 2020

Cited by 27 | Viewed by 13444

Abstract

Despite being largely preventable through early vaccination and screening strategies, cervical cancer is the most common type of gynecological malignancy worldwide and constitutes one of the leading causes of cancer deaths in women. Patients with advanced or recurrent disease have a very poor [...] Read more.

Despite being largely preventable through early vaccination and screening strategies, cervical cancer is the most common type of gynecological malignancy worldwide and constitutes one of the leading causes of cancer deaths in women. Patients with advanced or recurrent disease have a very poor prognosis; hence, novel therapeutic modalities to improve clinical outcomes in cervical malignancy are needed. In this regard, targeted gene delivery therapy is presented as a promising approach, which leads to the development of multiple strategies focused on different aspects. These range from altered gene restoration, immune system potentiation, and oncolytic virotherapy to the use of nanotechnology and the design of improved and enhanced gene delivery systems, among others. In the present manuscript, we review the current progress made in targeted gene delivery therapy for cervical cancer, the advantages and drawbacks and their clinical application. At present, multiple targeted gene delivery systems have been reported with encouraging preclinical results. However, the translation to humans has not yet shown a significant clinical benefit due principally to the lack of efficient vectors. Real efforts are being made to develop new gene delivery systems, to improve tumor targeting and to minimize toxicity in normal tissues. Full article

(This article belongs to the Special Issue Cervical Carcinoma)

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