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9 pages, 269 KiB

Open AccessArticle

Women with Cervical High-Risk Human Papillomavirus: Be Aware of Your Anus! The ANGY Cross-Sectional Clinical Study

by Martine Jacot-Guillarmod, Vincent Balaya, Jérôme Mathis, Martin Hübner, Fabian Grass, Matthias Cavassini, Christine Sempoux, Patrice Mathevet and Basile Pache

Cancers 2022, 14(20), 5096; https://doi.org/10.3390/cancers14205096 - 18 Oct 2022

Cited by 3 | Viewed by 1442

Abstract

Anogenital human papillomaviruses (HPV) are highly prevalent in sexually active populations, with HR-HPV being associated with dysplasia and cancers. The consequences of cervical HPV infection are well-known, whereas those of the anus are less clear. The correlation of cervical and anal HPVs with [...] Read more.

Anogenital human papillomaviruses (HPV) are highly prevalent in sexually active populations, with HR-HPV being associated with dysplasia and cancers. The consequences of cervical HPV infection are well-known, whereas those of the anus are less clear. The correlation of cervical and anal HPVs with the increasing number of anal cancers in women has not been studied yet. The objective of our prospective study was to determine whether cervical and anal HPV correlated in a cohort of women recruited in a university hospital in Switzerland. Recruitment was conducted in the gynecology clinic, the colposcopy clinic, and the HIV clinic. Cervical and anal HPV genotyping and cytology were performed. Overall, 275 patients were included (360 were initially planned), and among them, 102 (37%) had cervical HR-HPV. Patients with cervical HR-HPV compared to patients without cervical HR-HPV were significantly younger (39 vs. 44 yrs, p < 0.001), had earlier sexual intercourse (17.2 vs. 18.3 yrs, p < 0.01), had more sexual partners (2.9 vs. 2.2, p < 0.0001), more dysplastic cervical cytology findings (42% vs. 19%, p < 0.0001) and higher prevalence of anal HR-HPV (59% vs. 24%, p < 0.0001). Furthermore, the HR-HPV group reported more anal intercourse (44% vs. 29%, p < 0.015). Multivariate analysis retained anal HR-HPV as independent risk factor for cervical HR-HPV (OR3.3, CI 1.2–9.0, p = 0.02). The results of this study emphasize that it is of upmost importance to screen women for anal HR-HPV when diagnosing cervical HR-HPV. Full article

(This article belongs to the Special Issue Cervical Cancer Screening and Treatment in the 21st Century)

7 pages, 386 KiB

Open AccessArticle

Impact of the Coronavirus Disease 2019 (COVID-19) Pandemic on Cervical Cancer Screening in Gynecological Practices in Germany

by Niklas Gremke, Sebastian Griewing, Markus Felgentreff, Karel Kostev and Matthias Kalder

Cancers 2022, 14(19), 4820; https://doi.org/10.3390/cancers14194820 - 2 Oct 2022

Cited by 6 | Viewed by 1601

Abstract

Purpose: the aim of this cross-sectional study was to analyze the impact of the COVID-19 pandemic on Cervical Cancer Screening (CCS) in gynecological practices in Germany. Methods: The basis of the analysis was the Uniform Evaluation Standard (EBM) of the Statutory [...] Read more.

Purpose: the aim of this cross-sectional study was to analyze the impact of the COVID-19 pandemic on Cervical Cancer Screening (CCS) in gynecological practices in Germany. Methods: The basis of the analysis was the Uniform Evaluation Standard (EBM) of the Statutory Health Insurance Scheme. This cross-sectional study included all women aged ≥20 years with at least one CCS (clinical and cytological examination) in 223 gynecological practices in Germany during the period 2018–2021. The number of patients with CCS per practice was shown for each year. The average number of patients per year was compared between the pre-pandemic time period (2018, 2019) and the pandemic time period (2020, 2021) using Wilcoxon tests. Analyses were conducted separately for clinical investigations and cytological investigations and were also stratified by age group (20–34, 35–50, >50 years). Results: CCS in gynecological practices significantly decreased in Germany between the pre-pandemic time period of 2018–2019 and the pandemic years of 2020–2021. This decrease was observed in all age groups but was stronger in women aged 20–34 (−25.6%) and weaker in women aged >50 (−15.2%). Conclusions: We found a statistically and clinically relevant decrease of patients receiving CCS in gynecological practices in Germany. This finding is even more exceptional because the new screening algorithm with direct invitations for each patient started in 2020 and was supposed to lead to a higher number of patients in its first years. However, the observed decline in the detection of cervical precancer lesions may lead to increased cervical cancer burden. Risk-based screening strategies and further measures are necessary to adapt to the ongoing COVID-19 pandemic and return to pre-pandemic CCS numbers. Full article

(This article belongs to the Special Issue Cervical Cancer Screening and Treatment in the 21st Century)

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13 pages, 1576 KiB

Open AccessArticle

Does the New FIGO 2018 Staging System Allow Better Prognostic Differentiation in Early Stage Cervical Cancer? A Dutch Nationwide Cohort Study

by Mieke L. G. Ten Eikelder, Floor Hinten, Anke Smits, Maaike A. Van der Aa, Ruud L. M. Bekkers, Joanna IntHout, Hans H. B. Wenzel and Petra L. M. Zusterzeel

Cancers 2022, 14(13), 3140; https://doi.org/10.3390/cancers14133140 - 27 Jun 2022

Cited by 2 | Viewed by 1705

Abstract

The FIGO 2018 staging system was introduced to allow better prognostic differentiation in cervical cancer, causing considerable stage migration and affecting treatment options. We evaluated the accuracy of the FIGO 2018 staging in predicting recurrence free (RFS) and overall survival (OS) compared to [...] Read more.

The FIGO 2018 staging system was introduced to allow better prognostic differentiation in cervical cancer, causing considerable stage migration and affecting treatment options. We evaluated the accuracy of the FIGO 2018 staging in predicting recurrence free (RFS) and overall survival (OS) compared to FIGO 2009 staging in clinically early stage cervical cancer. We conducted a nationwide retrospective cohort study, including 2264 patients with preoperative FIGO (2009) IA1, IA2 and IB1 cervical cancer between 2007–2017. Kaplan–Meier analyses were used to assess survival outcomes. Logistic regression was used to assess risk factors for lymph node metastasis and parametrial invasion. Stage migration occurred in 48% (22% down-staged, 26% up-staged). Survival data of patients down-staged from IB to IA1/2 disease were comparable with FIGO 2009 IA1/2 and better than patients remaining stage IB1. LVSI, invasion depth and parametrial invasion were risk factors for lymph node metastases. LVSI, grade and age were associated with parametrial invasion. In conclusion, the FIGO 2018 staging system accurately reflects prognosis in early stage cervical cancer and is therefore more suitable than the FIGO 2009 staging. However subdivision in IA1 or IA2 based on presence or absence of LVSI instead of depth of invasion would have improved accuracy. For patients down-staged to IA1/2, less radical surgery seems appropriate, although LVSI and histology should be considered when determining the treatment plan. Full article

(This article belongs to the Special Issue Cervical Cancer Screening and Treatment in the 21st Century)

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11 pages, 2215 KiB

Open AccessArticle

Providing Patients with Locally Advanced Cervical Cancer Access to Brachytherapy: Experience from a Referral Network for Women Treated in Overseas France

by Rita Bentahila, Elie Rassy, Samir Achkar, Florence Sacino, Stefanos Bougas, Alexis Vallard, Vincent Vinh-Hung, Johan Encaoua, Pierre Gustin, Sylvie Mengue, Patricia Pautier, Philippe Morice, Sébastien Gouy, Sophie Espenel, Eric Deutsch and Cyrus Chargari

Cancers 2022, 14(12), 2935; https://doi.org/10.3390/cancers14122935 - 14 Jun 2022

Cited by 1 | Viewed by 1745

Abstract

Image-guided adaptive brachytherapy (IGABT) is part of the standard of care for locally advanced cervical cancer (LACC). Access to IGABT is limited in many regions, thus leading to treatment care disparities. We report the experience of a referral network for women with LACC [...] Read more.

Image-guided adaptive brachytherapy (IGABT) is part of the standard of care for locally advanced cervical cancer (LACC). Access to IGABT is limited in many regions, thus leading to treatment care disparities. We report the experience of a referral network for women with LACC between radiotherapy facilities in Overseas France and Gustave Roussy. This is a retrospective review of patients with LACC referred to Gustave Roussy, for pulsed-dose-rate (PDR) image-guided adaptive BT after initial radiation therapy in the French overseas between 2014 and 2021. Sixty-four patients were eligible to receive IGABT. Overall treatment time (OTT) was 60.5 days (IQR: 51–68.5). The median follow-up time was 17 months. At two years, estimated probabilities of LC, progression-free survival, and overall survival (OS) were 94.6% (95% CI: 88.9–100.0%), 72.7% (95% CI: 61.1–86.5%), and 82.5% (95% CI: 72.0–94.5%). In multivariable analysis, a D90CTVHR < 85GyEQD2 and a CTVHR volume > 40 cm³ were significant for poorer PFS (p = 0.001 and p = 0.009, respectively) and poorer OS (p = 0.004 and p = 0.004). The centralization of this advanced technique to expert centers requires a well-defined workflow and appropriate dimensioning of resources to minimize OTT. Full article

(This article belongs to the Special Issue Cervical Cancer Screening and Treatment in the 21st Century)

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12 pages, 258 KiB

Open AccessArticle

Clinical Epidemiology of Microinvasive Cervical Carcinoma in an Italian Population Targeted by a Screening Programme

by Lauro Bucchi, Silvano Costa, Silvia Mancini, Flavia Baldacchini, Orietta Giuliani, Alessandra Ravaioli, Rosa Vattiato, Federica Zamagni, Paolo Giorgi Rossi, Cinzia Campari, Debora Canuti, Priscilla Sassoli de Bianchi, Stefano Ferretti, Fabio Falcini and on behalf of the Emilia-Romagna Region Workgroup for Cervical Screening Evaluation

Cancers 2022, 14(9), 2093; https://doi.org/10.3390/cancers14092093 - 22 Apr 2022

Cited by 2 | Viewed by 1333

Abstract

(1) Background: This population-based study aimed at identifying the factors associated with the likelihood of detection of stage IA cervical carcinoma—versus the detection of stage IB through IV cervical carcinoma—and the patterns of surgical treatment. (2) Methods: Between 1995–2016, 3750 patients living in [...] Read more.

(1) Background: This population-based study aimed at identifying the factors associated with the likelihood of detection of stage IA cervical carcinoma—versus the detection of stage IB through IV cervical carcinoma—and the patterns of surgical treatment. (2) Methods: Between 1995–2016, 3750 patients living in the Emilia-Romagna Region (northern Italy) were registered with cervical carcinoma, including 2942 eligible patients (median age, 53). Multivariate analysis was performed using binary logistic regression models. (3) Results: The likelihood of stage IA cervical carcinoma (n = 876, 29.8%) did not change over time, decreased with increasing patient age, and was lower for patients with adenocarcinoma and grade 3–4 disease. Three hundred and fifty (40.0%) patients had a conservative treatment, 317 (36.2%) had hysterectomy, 197 (22.5%) had hysterectomy with lymph node dissection (LND), and 12 (1.4%) had a conservative treatment with LND. The proportion of hysterectomy decreased from 70.6% in 1995–1999 to 46.9% in 2011–2016. The likelihood of hysterectomy increased above the age of 40. Among screening-aged (25–64 years) patients, the likelihood of hysterectomy did not differ between screen-detected and non-screen-detected ones. Hysterectomy was increasingly combined with LND. High tumour grade was the strongest determinant of LND during hysterectomy. (4) Conclusions: This study provided a multifaceted overview of stage IA cervical carcinoma over the last decades. Full article

(This article belongs to the Special Issue Cervical Cancer Screening and Treatment in the 21st Century)

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15 pages, 4160 KiB

Open AccessArticle

Lymph Node Involvement in Early-Stage Cervical Cancer: Is Lymphangiogenesis a Risk Factor? Results from the MICROCOL Study

by Matteo Tantari, Stefano Bogliolo, Matteo Morotti, Vincent Balaya, Florent Bouttitie, Annie Buenerd, Laurent Magaud, Fabrice Lecuru, Benedetta Guani, Patrice Mathevet and on behalf of the SENTICOL Group

Cancers 2022, 14(1), 212; https://doi.org/10.3390/cancers14010212 - 2 Jan 2022

Cited by 12 | Viewed by 2851

Abstract

Background: In patients with cervical cancer, the presence of tumoral lymph-vascular space invasion (LVSI) is the main risk factor for pelvic lymph node metastasis (PLNM). The objective of this study was to evaluate the presence of several markers of lymphangiogenesis in early-stage cervical [...] Read more.

Background: In patients with cervical cancer, the presence of tumoral lymph-vascular space invasion (LVSI) is the main risk factor for pelvic lymph node metastasis (PLNM). The objective of this study was to evaluate the presence of several markers of lymphangiogenesis in early-stage cervical cancer and their correlation with PLNM and tumoral recurrence. Materials and Methods: Seventy-five patients with early-stage cervical carcinoma underwent sentinel lymph node (SLN) sampling in association with complete pelvic lymph node dissection. Primary tumors were stained with the following markers: Ki67, D2-40, CD31 and VEGF-C. A 3-year follow-up was performed to evaluate the disease-free survival. Results: Overall, 14 patients (18.6%) had PLNM. Positive LVSI was seen in 29 patients (38.6%). There was a significant correlation between LVSI evidenced by H/E staining and PLNM (p < 0.001). There was no correlation between high Ki67, CD31, D2-40, and VEGF-C staining with PLNM or tumor recurrence. Conclusions: Our data support that lymphatic spread does not require the proliferation of new lymphatic endothelial cells in early-stage cervical cancer. These results emphasize the importance of pre-existing peritumoral lymphatic vessels in the metastatic process in early cervical cancer. None of the markers of lymphangiogenesis and proliferation assessed in this study were predictive of PLNM or recurrence. Full article

(This article belongs to the Special Issue Cervical Cancer Screening and Treatment in the 21st Century)

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Review

Jump to: Research

40 pages, 3654 KiB

Open AccessReview

Gene Therapy for Malignant and Benign Gynaecological Disorders: A Systematic Review of an Emerging Success Story

by Ekati Drakopoulou, Nicholas P. Anagnou and Kalliopi I. Pappa

Cancers 2022, 14(13), 3238; https://doi.org/10.3390/cancers14133238 - 30 Jun 2022

Cited by 7 | Viewed by 3358

Abstract

Despite the major advances in screening and therapeutic approaches, gynaecological malignancies still present as a leading cause of death among women of reproductive age. Cervical cancer, although largely preventable through vaccination and regular screening, remains the fourth most common and most lethal cancer [...] Read more.

Despite the major advances in screening and therapeutic approaches, gynaecological malignancies still present as a leading cause of death among women of reproductive age. Cervical cancer, although largely preventable through vaccination and regular screening, remains the fourth most common and most lethal cancer type in women, while the available treatment schemes still pose a fertility threat. Ovarian cancer is associated with high morbidity rates, primarily due to lack of symptoms and high relapse rates following treatment, whereas endometrial cancer, although usually curable by surgery, it still represents a therapeutic problem. On the other hand, benign abnormalities, such as fibroids, endometriosis, placental, and embryo implantation disorders, although not life-threatening, significantly affect women’s life and fertility and have high socio-economic impacts. In the last decade, targeted gene therapy approaches toward both malignant and benign gynaecological abnormalities have led to promising results, setting the ground for successful clinical trials. The above therapeutic strategies employ both viral and non-viral systems for mutation compensation, suicide gene therapy, oncolytic virotherapy, antiangiogenesis and immunopotentiation. This review discusses all the major advances in gene therapy of gynaecological disorders and highlights the novel and potentially therapeutic perspectives associated with such an approach. Full article

(This article belongs to the Special Issue Cervical Cancer Screening and Treatment in the 21st Century)

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26 pages, 1678 KiB

Open AccessReview

Review of the Standard and Advanced Screening, Staging Systems and Treatment Modalities for Cervical Cancer

by Siaw Shi Boon, Ho Yin Luk, Chuanyun Xiao, Zigui Chen and Paul Kay Sheung Chan

Cancers 2022, 14(12), 2913; https://doi.org/10.3390/cancers14122913 - 13 Jun 2022

Cited by 12 | Viewed by 7223

Abstract

Cancer arising from the uterine cervix is the fourth most common cause of cancer death among women worldwide. Almost 90% of cervical cancer mortality has occurred in low- and middle-income countries. One of the major aetiologies contributing to cervical cancer is the persistent [...] Read more.

Cancer arising from the uterine cervix is the fourth most common cause of cancer death among women worldwide. Almost 90% of cervical cancer mortality has occurred in low- and middle-income countries. One of the major aetiologies contributing to cervical cancer is the persistent infection by the cancer-causing types of the human papillomavirus. The disease is preventable if the premalignant lesion is detected early and managed effectively. In this review, we outlined the standard guidelines that have been introduced and implemented worldwide for decades, including the cytology, the HPV detection and genotyping, and the immunostaining of surrogate markers. In addition, the staging system used to classify the premalignancy and malignancy of the uterine cervix, as well as the safety and efficacy of the various treatment modalities in clinical trials for cervical cancers, are also discussed. In this millennial world, the advancements in computer-aided technology, including robotic modules and artificial intelligence (AI), are also incorporated into the screening, diagnostic, and treatment platforms. These innovations reduce the dependence on specialists and technologists, as well as the work burden and time incurred for sample processing. However, concerns over the practicality of these advancements remain, due to the high cost, lack of flexibility, and the judgment of a trained professional that is currently not replaceable by a machine. Full article

(This article belongs to the Special Issue Cervical Cancer Screening and Treatment in the 21st Century)

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