Cervical cancer during the covid pandemic: Are patients presenting with more advanced or larger tumours?

OBJECTIVES: Concerns were raised by clinicians at the Oxford Gynaecological Cancer MDT that there was an increasing number of women presenting with large cervical tumours requiring chemo-radiotherapy, possibly due to delays associated with the COVID pandemic. This audit was undertaken to assess whether this was a real event. STUDY DESIGN: This retrospective cohort study collated the data from the central pathology service covering Oxfordshire, in the Oxford Gynaecological cancer centre. The control population consisted of patients treated during the 2 years pre-pandemic (1st Jan 2018-31 Dec 2019) and the study group the 2-year pandemic period (1st Jan 2020 until 31st December 2021). A total of 153 patients (74 control and 79 study) were diagnosed of cervical cancer during the study period. Variables included in the analysis were age, pathway of referral and diagnosis (cytology or clinical), FIGO stage, tumour histology, tumour size (using maximum diameter on MRI) and treatment. Student's t-test was used for continuous and discrete variables, respectively. The X2 test was used for the statistical analysis of proportions. RESULTS: There was no statistically significant differences was noted in the referral pathways during both periods. Statistically significant stage migration from FIGO stage II to III was detected (p < 0.05), though no statistically significant change in tumour size. However, the pattern of tumour volume on case-to-case comparison elicited more cases with larger volumes during the pandemic periods. CONCLUSIONS: Referral pathways of diagnosed cancer cervix was not affected during the pandemic in Oxfordshire. Therapeutic treatment numbers were unchanged - but some changes in tumour volume were likely the reason for the impression more such cases. Whether the stage shift noted here is representative of the wider population requires further studies.

Impact of COVID-19 in Cervical and Breast Cancer Screening and Systemic Treatment in São Paulo, Brazil: An Interrupted Time Series Analysis.

PURPOSE: COVID-19 caused a disruption in cancer management around the world, resulting in an estimated excess burden secondary to screening disruption and excess lag time for treatment initiation. METHODS: We gathered information from primary reimbursement data sets of the public health system of São Paulo, Brazil, from April 2020 to November 2021, and compared these data with those of the pre-COVID-19 period. We used an interrupted time series model to estimate the effect of the COVID-19 pandemic on the rate of key procedures of breast and cervical cancer health care chain. RESULTS: We estimated that 1,149,727, 2,693, and 713,616 pap smears, conizations, and mammograms, respectively, were missed or delayed during the COVID-19 pandemic, compared with those in the years immediately before the COVID-19 stay-at-home restrictions. Specifically, we observed an acute decrease of procedures after the COVID-19 stay-at-home restrictions, with a trend to recovery in the long term. Regarding the systemic treatment analysis, we observed a 25% reduction in the rate of initiation of adjuvant systemic treatment for early breast cancer (stage I/II). However, we did not find a clear effect on the other settings of systemic treatment for breast cancer. We estimated an excess of 156 patients starting palliative care for cervical cancer after the COVID-19 stay-at-home restrictions. CONCLUSION: The COVID-19 pandemic significantly reduced the performance rate of pap smears, conizations, and mammograms. The initiation of adjuvant treatment for early-stage breast cancer was most susceptible to COVID-19's health system disruption. Furthermore, the downward trend of treatment of advanced cervical cancer was interrupted. Therefore, public health policies are urgently needed to decrease the incidence of advanced cervical and breast cancers caused by delayed diagnosis and treatment initiation.The COVID-19 control policies resulted in reduction of cancer patients' delivery of care. This study evaluated the pandemic's influence in key procedures of breast and cervical cancer chain of care in São Paulo, Brazil. We observed a substantial reduction in the number of mammograms, pap smears, and conizations performed since the onset of the COVID-19 pandemic. In addition, stage I and II breast cancer adjuvant treatment presented a reduced realization rate, whereas palliative treatment delivered for advanced cervical cancer increased. Our results support the need for public health policies focused on mitigating the long-term effects of COVID-19 in cancer-related mortality.

Hands-On Training Courses for Cervical Cancer Screening, Diagnosis, and Treatment Procedures in Low- and Middle-Income Countries.

In 2018, there were approximately 570,000 new cases of cervical cancer worldwide. More than 85% of cases occurred in low- and middle-income countries (LMICs), primarily because of poor access to screening and a limited number of medical providers trained to diagnose and treat cervical precancerous lesions. Our objective was to provide locally arranged, hands-on training courses for medical providers in LMICs to learn to perform cervical cancer screening, diagnosis, and treatment procedures. The courses included didactic lectures and hands-on training stations using low-cost simulation models developed by bioengineers and students at Rice University in Houston, TX, United States, and the Malawi Polytechnic in Blantyre, Malawi. The hands-on training stations included visual inspection with acetic acid (VIA), colposcopy, cervical biopsy, endocervical curettage, loop electrosurgical excision procedure (LEEP), and thermal ablation. Provider pre- and postcourse confidence levels in performing the procedures were evaluated. From February 2017 to January 2020, we arranged 15 hands-on training courses in seven cities across six countries (El Salvador, Mozambique, Trinidad and Tobago, Lesotho, Malawi, and Nepal). Overall, there were 506 participants. The average number of participants per course was 38 (range 19-92). The participants included doctors, nurses, and midwives. The course duration varied from 1 to 3 days. Increased confidence in performing VIA, colposcopy and cervical biopsy, ablation, and LEEP was reported by 69%, 71%, 61%, and 76% of participants, respectively. Our findings suggest that locally arranged, hands-on cervical cancer prevention training courses in LMICs can improve provider confidence in performing cervical cancer screening, diagnosis, and treatment procedures. These courses are part of a larger strategy to build local capacity for delivering and improving cervical cancer prevention services in LMICs.

Uterine cervix metastasis from primary colon adenocarcinoma: a case report and review of the literature.

INTRODUCTION: Metastases to the female genital tract from extragenital primary tumors are unusual. We report a rare case of uterine cervix metastasis from colon adenocarcinoma and discuss diagnostic and therapeutic issues. CASE REPORT: We report a case of a 38-year-old North African Caucasian woman treated for a non-metastatic colon adenocarcinoma. She had a sigmoidectomy and incomplete adjuvant chemotherapy. Six months later, she consulted with vaginal bleeding caused by a cervical tumor, which was confirmed to be metastatic disease, and the patient underwent decompressive and hemostatic radiotherapy. CONCLUSION: Uterine cervix metastasis from primary colon adenocarcinoma is rare. The resection remains the standard protocol for the local treatment of resectable metastatic disease. Otherwise, systemic therapy is the preferable option.

Therapeutic DNA Vaccines against HPV-Related Malignancies: Promising Leads from Clinical Trials.

In 2014 and 2021, two nucleic-acid vaccine candidates named MAV E2 and VGX-3100 completed phase III clinical trials in Mexico and U.S., respectively, for patients with human papillomavirus (HPV)-related, high-grade squamous intraepithelial lesions (HSIL). These well-tolerated but still unlicensed vaccines encode distinct HPV antigens (E2 versus E6+E7) to elicit cell-mediated immune responses; their clinical efficacy, as measured by HSIL regression or cure, was modest when compared with placebo or surgery (conization), but both proved highly effective in clearing HPV infection, which should help further optimize strategies for enhancing vaccine immunogenicity, toward an ultimate goal of preventing malignancies in millions of patients who are living with persistent, oncogenic HPV infection but are not expected to benefit from current, prophylactic vaccines. The major roadblocks to a highly efficacious and practical product remain challenging and can be classified into five categories: (i) getting the vaccines into the right cells for efficient expression and presentation of HPV antigens (fusion proteins or epitopes); (ii) having adequate coverage of oncogenic HPV types, beyond the current focus on HPV-16 and -18; (iii) directing immune protection to various epithelial niches, especially anogenital mucosa and upper aerodigestive tract where HPV-transformed cells wreak havoc; (iv) establishing the time window and vaccination regimen, including dosage, interval and even combination therapy, for achieving maximum efficacy; and (v) validating therapeutic efficacy in patients with poor prognosis because of advanced, recurrent or non-resectable malignancies. Overall, the room for improvements is still large enough that continuing efforts for research and development will very likely extend into the next decade.

The Cervical Cancer Research Network (Gynecologic Cancer InterGroup) roadmap to expand research in low- and middle-income countries.

Cervical cancer is a global health problem which disproportionally affects women in low- and middle- income countries. The World Health Organization recently launched its global strategy to eliminate this disease in the next two decades. For those women diagnosed today with cervical cancer better strategies are needed to improve outcome and reduce treatment-related morbidity. Clinical trials are critical to shaping future treatment, and much has been achieved already. However, such opportunities are limited in low resource settings, and the Cervical Cancer Research Network is dedicated to expanding access to new technologies in surgery, radiation, and medical oncology. In this article we review the status of the trials portfolio and outline future objectives, including the launch of a number of research grants for aspiring or established researchers in low- and middle-income settings.

The COVID-19 pandemic and its implications for cervical cancer treatment and prevention in Zimbabwe: perspectives and recommendations.

Cervical cancer is the leading gynaecological malignancy in Zimbabwe, constituting 33% of all female cancers in 2016. Primary prevention through vaccination and secondary prevention through screening are important public health interventions to reduce the cervical cancer burden. Unfortunately, the ongoing COVID-19 pandemic has brought unprecedented challenges to healthcare delivery, posing threats to prevention efforts at a time when the public health sector is extremely fragile. The fragility of the sector has complicated treatment for cervical cancer before and during the COVID-19 pandemic, and is expected to worsen beyond the pandemic. A multi-sectoral intersection between public health experts, clinicians and communities is urgently required to restore preventive and treatment services for cervical cancer and reduce the increased burden, morbidity and mortality stemming indirectly from the pandemic.

The impact of the COVID-19 pandemic on the Ontario Cervical Screening Program, colposcopy and treatment services in Ontario, Canada: a population-based study.

OBJECTIVE: To describe the immediate impact of the COVID-19 pandemic on cervical screening, colposcopy and treatment volumes in Ontario, Canada. DESIGN: Population-based retrospective observational study. SETTING: Ontario, Canada. POPULATION: People with a cervix age of 21-69 years who completed at least one cervical screening cytology test, colposcopy or treatment procedure for cervical dysplasia between January 2019 and August 2020. METHODS: Administrative databases were used to compare cervical screening cytology, colposcopy and treatment procedure volumes before (historical comparator) and during the first 6 months of the COVID-19 pandemic (March-August 2020). MAIN OUTCOME MEASURES: Changes in cervical screening cytology, colposcopy and treatment volumes; individuals with high-grade cytology awaiting colposcopy. RESULTS: During the first 6 months of the COVID-19 pandemic, the monthly average number of cervical screening cytology tests, colposcopies and treatments decreased by 63.8% (range: -92.3 to -41.0%), 39.7% (range: -75.1 to -14.3%) and 31.1% (range: -43.5 to -23.6%), respectively, when compared with the corresponding months in 2019. Between March and August 2020, on average 292 (-51.0%) fewer high-grade cytological abnormalities were detected through screening each month. As of August 2020, 1159 (29.2%) individuals with high-grade screening cytology were awaiting follow-up colposcopy. CONCLUSIONS: The COVID-19 pandemic has had a substantial impact on key cervical screening and follow-up services in Ontario. As the pandemic continues, ongoing monitoring of service utilisation to inform system response and recovery is required. Future efforts to understand the impact of COVID-19-related disruptions on cervical cancer outcomes will be needed. TWEETABLE ABSTRACT: COVID-19 has had a substantial impact on cervical screening and follow-up services in Ontario, Canada.

Association between definitive chemoradiotherapy wait-time and survival in locally-advanced cervical cancer: Implications during the coronavirus pandemic.

OBJECTIVE: The current coronavirus pandemic caused a significant decrease in cancer-related encounters resulting in a delay in treatment of cancer patients. The objective of this study was to examine the survival effect of delay in starting concurrent chemo-radiotherapy (CCRT) in women with locally-advanced cervical cancer. METHODS: This is a retrospective observational study querying the National Cancer Database from 2004 to 2016. Women with stage IB2-IVA squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix who received definitive CCRT with known wait-time for CCRT initiation after cancer diagnosis were eligible (N=13,617). Cox proportional hazard regression model with restricted cubic spline transformation was fitted to assess the association between CCRT wait-time and all-cause mortality in multivariable analysis. RESULTS: The median wait-time to start CCRT was 6 (IQR 4-8) weeks. In a multivariable analysis, older age, non-Hispanic black and Hispanic ethnicity, recent year of diagnosis, Medicaid and uninsured status, medical comorbidities, and absence of nodal metastasis were associated with longer CCRT wait-time (P<.05). Women with aggressive tumor factors (poorer differentiation, large tumor size, nodal metastasis, and higher cancer stage) were more likely to have a short CCRT wait-time (P<.05). After controlling for the measured covariates, CCRT wait-time of 6.1-9.8 weeks was not associated with increased risk of all-cause mortality compared to a wait-time of 6 weeks. Similar association was observed when the cohort was stratified by histology, cancer stage, tumor size, or brachytherapy use. CONCLUSION: An implication of this study for the current coronavirus pandemic is that in the absence of aggressive tumor factors, a short period of wait-time to start definitive CCRT may not be associated with increased risk of mortality in women with locally-advanced cervical cancer.

Impact of COVID-19 on Outcomes for Patients With Cervical Cancer in India.

PURPOSE: The COVID-19 pandemic has placed unprecedented demands on the health system. This led to delays in the initiation and completion of cancer treatment. We assessed the long-term health consequences because of the delay in diagnosis and treatment for cervical cancer due to COVID-19 in India. METHODS: We used a Markov-model-based analysis assessing the lifetime health outcomes of the cohort of women population at risk from cervical cancer in India. The decrease in survival for those with the treatment interruption was calculated based on the number of days the treatment was extended beyond the standard duration. Furthermore, to model the impact of late diagnosis and delayed treatment initiation, the patients were assumed to have upstaged during the delay period, as per natural progression of disease. RESULTS: We estimate 2.52% (n = 795) to 3.80% (n = 2,160) lifetime increase in the deaths caused by cervical cancer with treatment restrictions ranging from 9 weeks to 6 months, respectively, as compared to no delay. On the contrary, 88-238 deaths because of COVID-19 disease are estimated to be saved during this restriction period among the patients with cervical cancer. Overall, the excess mortality because of cervical cancer led to 18,159-53,626 life-years being lost and an increase of 16,808-50,035 disability-adjusted life-years. CONCLUSION: Delays in diagnosis and treatment are likely to lead to more cervical cancer deaths as compared to COVID-19 mortality averted among the patients with cervical cancer. Health systems must reorganize in terms of priority setting for provision of care, starting with prioritizing the treatment of patients with early-stage cervical cancer, increasing use of teleconsultation, and strengthening the role of primary care physicians in provision of cancer care.

ESMO management and treatment adapted recommendations in the COVID-19 era: gynaecological malignancies.

The rapid spread of severe acute respiratory syndrome coronavirus 2 infection and its related disease (COVID-19) has required an immediate and coordinate healthcare response to face the worldwide emergency and define strategies to maintain the continuum of care for the non-COVID-19 diseases while protecting patients and healthcare providers. The dimension of the COVID-19 pandemic poses an unprecedented risk especially for the more vulnerable populations. To manage patients with cancer adequately, maintaining the highest quality of care, a definition of value-based priorities is necessary to define which interventions can be safely postponed without affecting patients' outcome. The European Society for Medical Oncology (ESMO) has endorsed a tiered approach across three different levels of priority (high, medium, low) incorporating information on the value-based prioritisation and clinical cogency of the interventions that can be applied for different disease sites. Patients with gynaecological cancer are at particular risk of COVID-19 complications because of their age and prevalence of comorbidities. The definition of priority level should be based on tumour stage and histology, cancer-related symptoms or complications, aim (curative vs palliative) and magnitude of benefit of the oncological intervention, patients' general condition and preferences. The decision-making process always needs to consider the disease-specific national and international guidelines and the local healthcare system and social resources, and a changing situation in relation to COVID-19 infection. These recommendations aim to provide guidance for the definition of deferrable and undeferrable interventions during the COVID-19 pandemic for ovarian, endometrial and cervical cancers within the context of the ESMO Clinical Practice Guidelines.

Alternative management for gynecological cancer care during the COVID-2019 pandemic: A Latin American survey.

OBJECTIVE: To determine the acceptance rate of treatment alternatives for women with either preinvasive conditions or gynecologic cancers during the COVID-19 pandemic among Latin American gynecological cancer specialists. METHODS: Twelve experts in gynecological cancer designed an electronic survey, according to recommendations from international societies, using an online platform. The survey included 22 questions on five topics: consultation care, preinvasive cervical pathology, and cervical, ovarian, and endometrial cancer. The questionnaire was distributed to 1052 specialists in 14 Latin American countries. A descriptive analysis was carried out using statistical software. RESULTS: A total of 610 responses were received, for an overall response rate of 58.0%. Respondents favored offering teleconsultation as triage for post-cancer treatment follow-up (94.6%), neoadjuvant chemotherapy in advanced stage epithelial ovarian cancer (95.6%), and total hysterectomy with bilateral salpingo-oophorectomy and defining adjuvant treatment with histopathological features in early stage endometrial cancer (85.4%). Other questions showed agreement rates of over 64%, except for review of pathology results in person and use of upfront concurrent chemoradiation for early stage cervical cancer (disagreement 56.4% and 58.9%, respectively). CONCLUSION: Latin American specialists accepted some alternative management strategies for gynecological cancer care during the COVID-19 pandemic, which may reflect the region's particularities. The COVID-19 pandemic led Latin American specialists to accept alternative management strategies for gynecological cancer care, especially regarding surgical decisions.

Recommendations for the surgical management of gynecological cancers during the COVID-19 pandemic - FRANCOGYN group for the CNGOF.

INTRODUCTION: In the context of the COVID-19 pandemic, specific recommendations are required for the management of patients with gynecologic cancer. MATERIALS AND METHOD: The FRANCOGYN group of the National College of French Gynecologists and Obstetricians (CNGOF) convened to develop recommendations based on the consensus conference model. RESULTS: If a patient with a gynecologic cancer presents with COVID-19, surgical management should be postponed for at least 15 days. For cervical cancer, radiotherapy and concomitant radiochemotherapy could replace surgery as first-line treatment and the value of lymph node staging should be reviewed on a case-by-case basis. For advanced ovarian cancers, neoadjuvant chemotherapy should be preferred over primary cytoreduction surgery. It is legitimate not to perform hyperthermic intraperitoneal chemotherapy during the COVID-19 pandemic. For patients who are scheduled to undergo interval surgery, chemotherapy can be continued and surgery performed after 6 cycles. For patients with early stage endometrial cancer of low and intermediate preoperative ESMO risk, hysterectomy with bilateral adnexectomy combined with a sentinel lymph node procedure is recommended. Surgery can be postponed for 1-2 months in low-risk endometrial cancers (FIGO Ia stage on MRI and grade 1-2 endometrioid cancer on endometrial biopsy). For patients of high ESMO risk, the MSKCC algorithm (combining PET-CT and sentinel lymph node biopsy) should be applied to avoid pelvic and lumbar-aortic lymphadenectomy. CONCLUSION: During the COVID-19 pandemic, management of a patient with cancer should be adapted to limit the risks associated with the virus without incurring loss of chance.