Search

A woman in her mid-20s presented with bleeding at 18 weeks gestation from a cervical ‘polyp’. Histopathology demonstrated a rare small cell neuroendocrine of the cervix. There were only 18 cases of neuroendocrine tumours of the cervix in and around pregnancy in the literature, so the evidence base for treatment was scarce. She was treated with neoadjuvant chemotherapy, using a regimen used for small cell neuroendocrine tumours of the lung, to allow for fetal lung maturity. Disease initially responded, then progressed and she was delivered at 32 weeks by caesarean radical hysterectomy. Adjuvant treatment included further chemotherapy and radical pelvic radiotherapy. The woman and her child are doing well over 6 years after treatment, although the woman has significant side effects of both radical surgery and radiotherapy. This case emphasises the need for excellent communication between multidisciplinary professionals, patients and their families and using external colleagues to help with rare clinical problems.

Rationale and Objectives To investigate the feasibility and value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and texture parameters of primary lesions and lymph nodes for predicting pelvic lymph node metastasis in patients with cervical cancer. Materials and Methods A total of 143 patients with cervical cancer confirmed by surgical pathology were analyzed retrospectively and 125 patients were enrolled in primary lesions study, 83 patients and 134 lymph nodes were enrolled in lymph nodes study. Patients and lymph nodes were randomly divided into training group and test group at a ratio of 2: 1. The IVIM-DWI parameters and 3D texture features of primary lesions and lymph nodes of all patients were measured. The least absolute shrinkage and selection operator algorithm, spearman's correlation analysis, independent two-sample t-test and Mann-Whitney U-test were used to select texture parameters. Multivariate Logistic regression analysis and receiver operating characteristic curves were used to model and evaluate diagnostic performances. Results In primary lesions study, model 1 was constructed by combining f value, original_shape_Sphericity and original_firstorder_Mean of primary lesions. In lymph nodes study, model 2 was constructed by combining short diameter, circular enhancement and rough margin of lymph nodes. Model 3 was constructed by combining ADC, f value and original_glszm_Small Area Emphasis of lymph nodes. The areas under curve of model 1, 2 and 3 in training group and test group were 0.882, 0.798, 0.907 and 0.862, 0.771, 0.937 respectively. Conclusion Models based on IVIM-DWI and texture parameters of primary lesions and lymph nodes both performed well in diagnosing pelvic lymph node metastasis of cervical cancer and were superior to morphological features of lymph nodes. Especially, parameters of lymph nodes showed higher diagnostic efficiency and clinical significance.

Functional imaging allows the evaluation of numerous biological properties that could be considered at all steps of the therapeutic management of patients treated with brachytherapy. Indeed, it enables better initial staging of the disease, and some parameters may also be used as predictive biomarkers for treatment response, allowing better selection of patients eligible for brachytherapy. It may also improve the definition of target volumes with the aim of dose escalations by dose-painting. Finally, it could be useful during the follow-up to assess response to treatment. In this review, we report how functional imaging is integrated at the present time during the brachytherapy procedure, and what are its potential future contributions in the main tumour locations where brachytherapy is recommended. Functional imaging has great potential in the contact of brachytherapy, but still, several issues remain to be resolved before integrating it into clinical practice, especially as a biomarker or in dose painting strategies.

Purpose: This study aimed to evaluate patient- and treatment-related risk factors for late persistent fatigue within the prospective, multicenter EMBRACE-I study.Methods and Materials: Fatigue was prospectively assessed (Common Terminology Criteria for Adverse Events, version 3) at baseline and during regular follow up in 993 patients with locally advanced cervical cancer after treatment with chemoradio-therapy and magnetic resonance imaging-guided brachytherapy. Risk factors for baseline and late persistent fatigue were evaluated with multivariable logistic regression. Late persistent fatigue was defined when either grade >= 1 or >= 2 was scored in at least half of the follow ups.Results: The median follow-up time was 57 months. Baseline fatigue grade >= 1/>= 2 (35.8%/6.3%, respectively) was associated with preexisting comorbidities, World Health Organization performance status, being underweight, severe pain, and tumor volume. Late persistent grade >= 1/>= 2 fatigue (36.3%/5.8%, respectively) was associated with patient-related factors (baseline fatigue, younger age, obesity) along with the size of irradiated volumes and the level of radiation doses from external beam radiation therapy (EBRT) and brachytherapy (EBRT: V43Gy, V57Gy; EBRT + brachytherapy: V60Gy equivalent dose in 2-Gy fractions). Large-volume lymph node (LN) boost increased the risk for late persistent fatigue grade >= 2 by 18% and 5% in patients with and without baseline fatigue, respectively, compared with no LN boost. The risk for late persistent fatigue grade >= 1 increased by 7% and 4% with V43Gy 3000 cm(3) in patients with and without baseline fatigue, respectively. Late persistent grade >= 1 fatigue occurred in 13% of patients without late persistent organ-related symptoms (gastrointestinal, genitourinary, and vaginal) versus 34% to 43%, 50% to 58%, and 73% in patients suffering from persistent symptoms involving 1, 2, or 3 organs, respectively.Conclusions: Late persistent fatigue occurs in a considerable number of patients after chemoradiotherapy, and is associated with patient-related factors, the size of volumes irradiated to intermediate and high EBRT and brachytherapy doses, and other persistent organ-related morbidity. These findings support the importance of ongoing efforts to better tailor the target dose and reduce irradiation of healthy tissue without compromising target coverage, using highly conformal EBRT and brachytherapy techniques. (C) 2021 Elsevier Inc. All rights reserved.

BACKGROUND: This study aims to understand how criminal-legal involved women from three U.S. cities navigate different health resource environments to obtain cervical cancer screening and follow-up care. METHODS: We conducted a cross-sectional study of women with criminal-legal histories from Kansas City KS/MO; Oakland, CA; and Birmingham, AL. Participants completed a survey that explored influences on cervical cancer prevention. Responses from all women with/without up-to-date cervical cancer screening and women with abnormal Pap testing who did/did not obtain follow-up care were compared. Proportions and associations were tested with chi-square or analysis of variance tests. Multivariable regression was performed to identify variables independently associated with up-to-date cervical cancer screening and reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: There were n = 510 participants, including n = 164 Birmingham, n = 108 Kansas City, and n = 238 Oakland women. Criminal-legal involved women in Birmingham (71.3%) and Kansas City (68.9%) were less likely to have up-to-date cervical cancer screening than women in Oakland (84.5%, p = 0.01). More women in Birmingham (14.6%) and Kansas City (16.7%) needed follow-up for abnormal Pap than women in Oakland (6.7%, p = 0.003), but there were no differences in follow-up rates. Predictors for up-to-date cervical cancer screening included access to a primary care provider (OR: 3.3, 95% CI: 1.4–7.7), health literacy (OR: 0.3, 95% CI: 0.2–0.7), and health behaviors, including avoiding tobacco (OR: 0.4, 95% CI: 0.1–0.9) and HPV vaccination (OR: 3.4, 95% CI: 1.0–10.9). CONCLUSIONS: Cervical cancer screening and follow-up varied by study site. The results suggest that patient level factors coupled with the complexity of accessing care in different health resource environments impact criminal-legal involved women's cervical cancer prevention behaviors.

Japan recently approved a quadrivalent human papillomavirus (HPV) vaccine for males, but the 9-valent vaccine has only been approved for females. Given the low female vaccination rate due to concerns about adverse events in Japan, quantifying the risks and benefits of the HPV vaccination for males may help in deciding whether to vaccinate adolescent boys in Japan. Using quality-adjusted life years, the risk-benefit ratio for an adolescent boy receiving the 9-valent HPV vaccination was calculated. The male HPV vaccination reduced the QALYs gained due to head and neck cancer, anal cancer, penile cancer, genital warts, and recurrent respiratory papillomatosis by 401.63, 20.38, 9.40, 28.79, and 69.13 per 100,000 vaccinated persons, respectively. The total risk of vaccination was 11.85. The risk-benefit ratio for a 12-year-old boy who received the HPV vaccination series was found to be 0.022 (benefit-risk ratio, 44.670). In the sensitivity analysis, the risk-benefit ratio ranged from 0.0001 to 0.11 for all scenarios. Hence, much larger benefits than risks linked with the male HPV vaccination were observed from an individual perspective. The results support the inclusion of sex-neutral HPV vaccinations into the national immunization program as well as strengthens the decision for adolescent boys to receive the vaccination.

As gender-affirming surgery is becoming more common, it is important for pathologists to recognize potential benign findings to avoid misinterpretation. Cervical transitional cell metaplasia and superficial clusters of small basophilic cells have been described in the context of gender-affirming testosterone therapy; these findings may be misdiagnosed as high-grade squamous intraepithelial lesions or endometrial cells on Pap smears. Prostatic metaplasia has been reported in the surface squamous epithelium of the vagina and the uterine cervix in individuals undergoing gender-affirming androgen therapy; this finding is often associated with NKX3.1-positive basal keratinocytes. The aim of this study was to assess the morphological and immunohistochemical features of the uterine cervix in gender-affirming hysterectomies in comparison with benign hysterectomies from cisgender women.We assessed the morphological and immunohistochemical features of the uterine cervix in 49 gender-affirming hysterectomies as compared with 57 hysterectomies from cisgender patients to establish the relative prevalences of surface prostatic metaplasia, NKX3.1-positive basal keratinocytes, transitional cell metaplasia, and small basophilic cells in the cervical squamous epithelium. The cervical tissue from the gender-affirming therapy cohort showed significantly higher prevalences of NKX3.1-positive basal keratinocytes (86% versus 1.8%), transitional cell metaplasia (80% versus 3.5%), superficial clusters of small basophilic cells (67% versus 7%), and surface prostatic metaplasia (43% versus 3.5%).NKX3.1-positive basal keratinocytes, transitional cell metaplasia, small basophilic cells and surface prostatic metaplasia are all more prevalent in the cervices of individuals receiving gender-affirming testosterone therapy; awareness of this fact allows pathologists to avoid the overdiagnosis of dysplasia or the recommendation of unnecessary follow-up procedures.

Background Cervical cancer is the leading cause of cancer among women in Tanzania, with approximately 10,000 new cases and 7,000 deaths annually. In April 2018, the Government of Tanzania introduced 2 doses of human papillomavirus (HPV) vaccine nationally to adolescent girls to prevent cervical cancer, following a successful 2-year pilot introduction of the vaccine in the Kilimanjaro Region. Methods We interviewed key informants at the national level in Tanzania from February to November 2019, using a semi-structured tool to better understand national decision-making and program implementation. We conducted a comprehensive desk review of HPV vaccine introduction materials and reviewed administrative coverage data. Results Ten key informants were interviewed from the Ministry of Health, Community Development, Gender, Elderly, and Children, the World Health Organization, and other partners, and HPV vaccine planning documents and administrative coverage data were reviewed during the desk review. Tanzania introduced HPV vaccine to a single-age cohort of 14-year-old girls, with the decision-making process involving the Tanzania Immunization Technical Advisory Group and the national Interagency Coordination Committee. HPV vaccine was integrated into the routine immunization delivery strategy, available at health facilities and through outreach services at community sites, community mobile sites (>10 km from the health facility), and primary and secondary schools. Pre-introduction activities included trainings and microplanning workshops for health workers and school personnel at the national, regional, council, and health facility levels. Over 6,000 health workers and 22,000 school personnel were trained nationwide. Stakeholder and primary health care committee meetings were also conducted at the national level and in each of the regions as part of the advocacy and communication strategy. Administrative coverage of the first dose of HPV vaccine at the end of 2019 was 78%, and second dose coverage was 49%. No adverse events following HPV vaccination were reported to the national level. Discussion Tanzania successfully introduced HPV vaccine nationally targeting 14-year-old girls, using routine delivery strategies. Continued monitoring of vaccination coverage will be important to ensure full 2-dose vaccination of eligible girls. Tanzania can consider periodic intensified vaccination and targeted social mobilization efforts, as needed.

Background In April 2018, Tanzania introduced the human papillomavirus (HPV) vaccine nationally to 14-year-old girls, utilizing routine delivery strategies (i.e. vaccinating girls at health facilities and community outreach, including schools). We sought to assess awareness, feasibility, and acceptability of the HPV vaccination program among health workers and community-level stakeholders. Methods We conducted cross-sectional in-person surveys among health workers, school personnel, community leaders, and council leaders in 18 council areas across six regions of Tanzania in October–November 2019. Regions were purposively selected to provide demographic, geographic, and vaccination coverage variability; sub-regional levels used random or stratified random sampling. Surveys included questions on HPV vaccine training and knowledge, delivery strategy, target population, and vaccine and program acceptability. Descriptive analysis was completed for all variables stratified by respondent groups. Results Across the 18 councils, there were 461 respondents, including health workers (165), school personnel (135), community leaders (143), and council leaders (18). Over half of each respondent group (50–78%) attended a training or orientation on HPV vaccine. Almost 75% of the health workers and school personnel respondent groups, and less than half (45%) of community leaders correctly identified the target age group for HPV vaccine. Most (80%) of the health workers indicated HPV vaccination was available at health facilities and schools; most (79%) indicated that the majority of girls receive HPV vaccine in school. Approximately half (52%) of all respondents reported hearing misinformation about HPV vaccine, but 97% of all respondents indicated that HPV vaccine was either “very accepted” or “somewhat accepted” in their community. Conclusion The HPV vaccination program in Tanzania was well accepted by community stakeholders in 18 councils; adequate knowledge of HPV vaccine and the HPV vaccination program was demonstrated by health workers and school personnel. However, continued technical support for integration of HPV vaccination as a routine immunization activity and reinforcement of basic knowledge about HPV vaccine in specific community groups is needed. The Tanzania experience provides an example of how this vaccine can be integrated into routine immunization delivery strategies and can be a useful resource for countries planning to introduce HPV vaccine as well as informing global partners on how to best support to countries in operationalizing their HPV vaccine introduction plans.

Summary Objective Radiotherapy remains an essential part of the management of locally advanced cervical cancer. Post-treatment surveillance allows for tumor response assessment and early detection of progressive prosecutions or local recurrences that may benefit from salvage treatment. The objective of this work is to assess the effectiveness of this therapeutic modality. Materials methods This is a retrospective study of 69 patients treated with concomitant radiation chemotherapy followed by high dose rate intracavitary brachytherapy. The tumor response was assessed by gynecologic physical examination at three months after the end of treatment. Results Median age of patients is 54.9 years (33–78 years). The most common histological type is squamous cell carcinoma (89.9%). The average dose received during external radiotherapy is 52.2 Gy (46–60 Gy). The average dose received during brachytherapy is 27.5 Gy (18–28 Gy). Three months after completion of treatment, 95.6% of patients had complete tumor remission, and only 4.4% had a tumor residue of 1 cm. Conclusion Radiation chemotherapy with brachytherapy allows for improved short-term local control in cervical cancer.

The HPV vaccine was introduced nationally in Malawi in 2019 and administered to 9-year-old girls. In order to drive uptake of the HPV vaccine Girl Effect utilised their youth brand, Zathu, to deliver messaging on the HPV vaccine. A Zathu 'mini magazine' was created specifically for 9-year-old girls to provide information, prompt household conversations and build empowerment around the HPV vaccine. This evaluation assessed the effectiveness of the Zathu mini magazine against two outcomes: (1) Girls are more informed & motivated to receive the HPV vaccine and (2) Girls talk to their caregivers about the HPV vaccine.A quasi-experimental approach was adopted using both qualitative and quantitative data collection to measure the results against these outcomes. The study found positive correlations between consumption of the Zathu mini magazine and awareness of cervical cancer, and positive attitudes towards the HPV vaccine among girls and parents in the exposed group compared to the non-exposed group. The Zathu mini magazine also encouraged household discussions on the HPV vaccine. Most significantly, consumption of the mini magazine was also positively correlated with uptake of the HPV vaccine among girls. This study highlights the value of girl-centred communications in demand generation for the HPV vaccine. There is potential to learn from and replicate this approach in other comparable settings.

Objective Studies on the effect of long-term use of combined oral contraceptives (COCs) on cervical dysplasia and/or cancer risk have been inconsistent. Less is known about the effects of other forms of hormonal contraception (HC). We examine whether HC use increases the risk of incident cervical intraepithelial neoplasia (CIN) 2, 3 and/or cancer after accounting for preexisting human papillomavirus (HPV) infection. Study Design Systematic review of prospective studies on HC use as risk factor for cervical dysplasia with HPV infection documented prior to outcome assessment including PubMed and EMBASE records between January 2000 and February 2020 (Prospero #CRD42019130725). Results Among 9 eligible studies, seven described recency and type of HC use and therefore comprise the primary analysis; two studies limit comparisons to ever versus never use and are summarized separately. All seven studies explored the relationship between oral contraceptive (OC) use and cervical dysplasia/cancer incidence: two found increased risk (adjusted odds ratio, aOR=1.5-2.7), one found no association but decreased risk when restricted to women with persistent HPV (adjusted hazard ratio=0.5), and four found no association. None of the seven studies differentiated between COC and progestin-only pills (POPs) by use recency or duration. The only study that included injectable progestin-only contraception (DMPA) found increased CIN3 incidence among current versus never users (aOR=1.6). The one study that included Norplant found no association. Two studies included intrauterine device (IUD) use, but did not differentiate between hormonal and copper IUDs, and found no association. Conclusion We found no consistent evidence that OC use is associated with increased risk for cervical dysplasia/cancer after controlling for HPV infection. There were too few studies of progestin-only injectables, implants or IUDs to assess their effect on cervical dysplasia/cancer risk. Implications Use of single self-reported HC measures and insufficient distinction by hormonal constituent cloud our understanding of whether some HCs increase risk for cervical cancer. Methodologically rigorous studies with distinct HCs measured as time-varying exposures are needed to inform cervical cancer prevention efforts and improve our understanding of cervical cancer etiology.

A WHO global strategy launched in November 2020 sets out an ambitious pathway towards the worldwide elimination of cervical cancer as a public health problem within the next 100 years. Achieving this goal will require investment in innovative approaches. This review aims to describe integrated approaches that combine human papillomavirus (HPV) vaccination and cervical cancer screening in low- and middle-income countries (LMIC), and their efficacy in increasing uptake of services. A systematic review was conducted analyzing relevant papers from Embase, Medline, CINAHL and CAB Global Health databases, as well as grey literature. Narrative synthesis was performed on the included studies. Meta-analysis was not appropriate due to the heterogeneity and nature of included studies. From 5,278 titles screened, 11 uncontrolled intervention studies from four countries (from Africa and east Asia) were included, all from the past 12 years. Four distinct typologies of integration emerged that either increased awareness of HPV and/or cervical cancer screening, and/or coupled the delivery of HPV vaccination and cervical cancer screening programs. The synthesis of findings suggests that existing HPV vaccination programs can be a useful pathway for educating mothers and other female caregivers about cervical cancer screening; through in person conversations with care providers (preferred) or take-home communications products. Integrated service delivery through outreach and mobile clinics may overcome geographic and economic barriers to access for both HPV vaccination and cervical cancer screening, however these require significant program and system resources. One study promoted HPV vaccination as part of integrated service delivery, but there were no other examples found that examined use of cervical cancer screening platforms to promote or educate on HPV vaccination. This review has demonstrated gaps in published literature on attempts to integrate HPV vaccination and cervical cancer screening. The most promising practices to date seem to relate to integrated health communications for cervical cancer prevention. Future research should further explore the opportunities for integrated health communications to support the efforts towards the new global cervical cancer elimination agenda, and costs and feasibility of integrated service delivery for underserved populations.

BACKGROUND To compare the rate, time and, pattern of recurrence of cervical cancer between patients with and without HIV infection and to determine factors predicting cervical cancer recurrence in patients evaluated by 18F-FDG-PET/CT. METHODS We reviewed the 18F-FDG-PET/CT images of patients with histologically proven cervical carcinoma who were presenting with suspected recurrence. We extracted epidemiologic data, previous treatment, histologic subtype, HIV status, viral load and CD4 counts from the electronic laboratory database and the referral form for the 18F-FDG-PET/CT study. RESULTS We studied 303 women including 112 HIV-infected patients. FIGO stage III disease was present in 131 patients. Of 198 patients with recurrence, 74 were HIV-infected while 124 were not (p=0.849). HIV infected patients were younger (41.99 ± 9.30 years) compared to HIV-uninfected (50.19 ± 11.09), p

Background Cervical cancer is a leading cause of cancer-associated mortality among women in India, with 96,922 new cases and 60,078 deaths each year, almost one-fifth of the global burden. In 2018, Sikkim state in India introduced human papillomavirus (HPV) vaccine for 9–13-year-old girls, primarily through school-based vaccination, targeting approximately 25,000 girls. We documented the program’s decision-making and implementation processes. Methods We conducted a post-introduction evaluation in 2019, concurrent with the second dose campaign, by interviewing key stakeholders (state, district, and local level), reviewing planning documents, and observing cold chain sites in two purposefully-sampled community areas in each of the four districts of Sikkim. Using standard questionnaires, we interviewed health and education officials, school personnel, health workers, community leaders, and age-eligible girls on program decision-making, planning, training, vaccine delivery, logistics, and communication. Results We conducted 279 interviews and 29 observations in eight community areas across four districts of Sikkim. Based on reported administrative data, Sikkim achieved >95% HPV vaccination coverage among targeted girls for both doses via two campaigns; no severe adverse events were reported. HPV vaccination was well accepted by all stakeholders; minimal refusal was reported. Factors identified for successful vaccine introduction included strong political commitment, statewide mandatory school enrollment, collaboration between health and education departments at all levels, and robust social mobilization strategies. Conclusions Sikkim successfully introduced the HPV vaccine to multiple-age cohorts of girls via school-based vaccination, demonstrating a model that could be replicated in other regions in India or similar low- and middle-income country settings.

The introduction of the Human papillomavirus (HPV) vaccine has shown potential to not only prevent cervical cancer but also drive adolescents’ access to other health care services, even in low-income countries. Few studies have been conducted to date to identify best practices and estimate the acceptance, operational challenges and benefits of including broader adolescent health interventions into immunization efforts, knowledge which is essential to supporting widespread integration. In this paper we review the efforts undertaken by the government of Togo to integrate adolescent health programming with the HPV vaccination roll out. With the support of partners (GAVI, WHO, UNFPA and UNICEF), the country successfully completed, in 2017, two years of an HPV vaccine demonstration project, which entailed vaccinating 10-year-old girls against HPV in two selected districts of the country and integrating a health education component focused on puberty education / menstrual hygiene and hand washing practice. Our study is a post-implementation program evaluation, using mixed methods to assess key questions of feasibility and acceptability of an integrated adolescent package of care. It showed that the HPV vaccination in conjunction with the health education sessions was well received by the majority of health care providers, teachers and parents. Our study confirmed that in Togo it proved feasible to combine education and HPV vaccination in school-based service delivery. However, more operational research is neded to understand how to increase the impact and sustainability of the co-delivery of interventions. We did not analyze the health impact and cost implications of the intervention, which will be an important consideration for scaling up such integration efforts alongside routine immunization.

Background: Cervical cancer screening with high-risk human papillomavirus (HrHPV) testing is being introduced. Most HrHPV infections are transient, requiring triage tests to identify individuals at highest risk for progression to cervical cancer. Head-to-head comparisons of available strategies for screening and triage are needed. Endometrial and ovarian cancers could be amenable to similar testing. Methods: Between 2016 and 2020, discarded cervical cancer screening specimens from women ages 25 to 65 undergoing screening at Kaiser Permanente Northern California were collected. Specimens were aliquoted, stabilized, and stored frozen. Human papillomavirus (HPV), cytology, and histopathology results as well as demographic and cofactor information were obtained from electronic medical records (EMR). Follow-up collection of specimens was conducted for 2 years, and EMR-based data collection was planned for 5 years. Results: Collection of enrollment and follow-up specimens is complete, and EMR-based follow-up data collection is ongoing. At baseline, specimens were collected from 54,957 HPV-positive, 10,215 HPV-negative/Pap-positive, and 12,748 HPV-negative/Pap-negative women. Clinical history prior to baseline was available for 72.6% of individuals, of which 53.9% were undergoing routine screening, 8.6% recently had an abnormal screen, 30.3% had previous colposcopy, and 7.2% had previous treatment. As of February 2021, 55.7% had one or more colposcopies, yielding 5,563 cervical intraepithelial neoplasia grade 2 (CIN2), 2,756 cervical intraepithelial neoplasia grade 3 (CIN3), and 146 cancer histopathology diagnoses. Conclusions: This robust population-based cohort study represents all stages of cervical cancer screening, management, and posttreatment follow-up. Impact: The IRIS study is a unique and highly relevant resource allowing for natural history studies and rigorous evaluation of candidate HrHPV screening and triage markers, while permitting studies of biomarkers associated with other gynecologic cancers.

Purpose: To evaluate patient-reported sexual outcomes after chemoradiation therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer in the observational, prospective, multicenter EMBRACE-I study. Methods and Materials: Sexual outcomes were assessed prospectively with the European Organization for Research and Treatment of Cancer Qualify of Life Questionnaire (EORTC-QLQ-CX24) at baseline and follow-up. Crude incidence and prevalence rates of sexual activity, vaginal functioning problems (dryness, shortening, tightening, pain during intercourse), and sexual enjoyment were evaluated. Associations between pain during intercourse and vaginal functioning problems or sexual enjoyment were calculated, pooling observations over all follow-ups (Spearman correlation coefficient). In patients who were frequently sexually active (≥50% of follow-ups), the effects of regular hormonal replacement therapy (HRT) on vaginal functioning problems were evaluated (Pearson χ 2). Results: The analysis involved 1045 patients with a median follow-up of 50 months. Sexual activity was reported by 22% of patients at baseline and by 40% to 47% of patients during follow-up (prevalence rates). Vaginal functioning problems in follow-up were dryness (18%-21%), shortening (15%-22%), tightening (16%-22%), pain during intercourse (9%-21%), and compromised enjoyment (37%-47%). Pain during intercourse was significantly associated with vaginal tightening (r = 0.544), shortening (r = 0.532), and dryness (r = 0.408) and negatively correlated with sexual enjoyment (r = –0.407). Regular HRT was associated with significantly less vaginal dryness (P = .015), shortening (P = .024), pain during intercourse (P = .003), and borderline higher sexual enjoyment (P = .062). Conclusions: Vaginal functioning problems are associated with pain and compromised sexual enjoyment. Further effort is required for the primary prevention of vaginal morbidity with dose optimization and adaptation. Secondary prevention strategies, including HRT for vaginal and sexual health after radiation therapy in locally advanced cervical cancer, should be considered and sexual rehabilitation programs should be developed further.

Background The introduction of primary HPV screening has doubled the number of colposcopy referrals because of the direct referral of HPV-positive women with a borderline or mild dyskaryosis (BMD) cytology (ASC-US/LSIL) triage test. Further risk-stratification is warranted to improve the efficiency of HPV-based screening. Methods This study evaluated the discriminative power of FAM19A4/miR124-2 methylation, HPV16/18 genotyping and HPV16/18/31/33/45 genotyping in HPV-positive women with BMD (n = 294) in two Dutch screening trials. Absolute CIN3+ risks and colposcopy referrals within one screening round were calculated. Results Methylation analysis discriminated well, yielding a CIN3+ risk of 33.1% after a positive result and a CIN3+ risk of 9.8% after a negative result. HPV16/18 and HPV16/18/31/33/45 genotyping resulted in a 27.6% and 24.6% CIN3+ risk after a positive result, and a 13.2% and 9.1% CIN3+ risk after a negative result. Colposcopy referral percentages were 41.2%, 43.2%, and 66.3% for FAM19A4/miR124-2 methylation, HPV16/18 and HPV16/18/31/33/45 genotyping, respectively. The CIN3+ risk after a negative result could be lowered to 2.8% by combining methylation and extended genotyping, at the expense of a higher referral percentage of 75.5%. Conclusion The use of FAM19A4/miR124-2 methylation and/or HPV genotyping in HPV-positive women with BMD can lead to a substantial reduction in the number of direct colposcopy referrals.

Objective: This study aimed to evaluate the effect of waiting time from diagnosis to initiation of definitive concurrent chemoradiation (CCRT) on overall survival in patients with cervical cancer. Methods: Patients with cervical cancer who had definitive CCRT between 2000 and 2017 were retrospectively reviewed. Time from pathological diagnosis to definitive CCRT was analyzed both as a continuous variable (per day) and as a categorical variable in 2 groups (Group 1 median, Group 2 > median). Patients with waiting time more than 60 days were excluded. Associations between waiting time, patients baseline characteristics, and survivals were analyzed using the Cox proportional-hazards model. Results: The median waiting time was 14 days (0-60). There were differences between Group 1 and Group 2 in age and type of chemotherapy. However, no significant difference was found in the FIGO stage, cell type, and the number of cycles of chemotherapy received during CCRT. Longer waiting time was associated with poorer overall survival on the Kaplan-Meir curve (Group 1 vs. Group 2, P = .042). On multivariate analysis, intervals as either a continuous variable (HR; 1. 023, 95% CI; 1.0061.040, P = .007) or a categorical variable (HR; 1.513, 95% CI; 1.0732.134, P = .018), FIGO stage, cell type, and the number of cycles of chemotherapy received during CCRT were significant independent prognostic factors for overall survival. Conclusion: Longer waiting time from pathological diagnosis to definitive CCRT was associated with worse overall survival. Our findings suggest that stakeholders in healthcare, including physicians and policymakers, should make an effort to minimize waiting time by rethinking factors involved in waiting time, such as referral time and time from decision making to treatment.

Objective Cervical cancer (CC) is a major public health problem in women, and its early detection can help reduce morbidity and mortality. The objective of this study was to compare serum levels of soluble major histocompatibility complex class I-related chain A (sMICA) levels in various body fluids between women diagnosed with CC and healthy women.Methods A case-control study was conducted at a tertiary care hospital and a cancer center in Kolhapur, India. Overall, 150 individuals (100 CC patients and 50 healthy women) participated after providing informed written consent. Demographic data, histopathology history, parity, and tumor, node, and metastasis (TNM) staging data were collected. Pap smears, saliva, blood, and urine samples were collected. Pap smears were examined microscopically, and sMICA levels in all samples were determined by enzyme-linked immunoassay (ELISA).Results The mean age of women with cervical cancer was 49.86±8.18 years. Squamous cell carcinoma (70%) was the most common histological variant in CC patients. Serum soluble sMICA levels differed significantly with parity and TNM staging (P

The adjuvant and post-surgical treatment of gynaecological cancers has historically been guided by the estimation of relapse risk based on clinicopathological factors determined at the time of cancer diagnosis. The recent advancement of genomic and molecular characterisation of gynaecological cancers has begun to shift paradigms in the selection of adjuvant treatment strategy. Recent data regarding the predictive and/or prognostic value of molecular tests in the treatment of advanced ovarian cancer as well as early stage endometrial cancer have been the first such examples to enter adjuvant treatment guidelines for these diseases. In this article, we discuss the current state and future development of molecular assays for gynaecological cancers and how they impact upon treatment selection for ovarian, endometrial and cervical cancers in the post-surgical setting.

OBJECTIVES This study aimed to evaluate the most updated worldwide distribution, risk factors, and temporal trends of cervical cancer for different countries and age groups. METHODS The Global Cancer Observatory database was retrieved for the age-standardized rates (ASRs, per 100,000 persons) for incidence and mortality of cervical cancer in 2018. The associations with risk factors were examined by multivariable regression analysis, adjusting for human development index (HDI) and gross domestic products (GDP) per capita. Joinpoint regression analysis was used to calculate the 10-year annual average percent change (AAPC) for incidence and mortality. RESULTS A total of 568,847 new cases (ASR, 13.1) and 311,365 deaths (ASR, 6.9) of cervical cancer were reported globally in 2018. The highest incidence and mortality were observed in Southern Africa (ASRs, 43.1 and 20.0) and countries with low HDI (ASRs, 29.8 and 23.0). Countries with higher incidence and mortality had lower HDI (β = -8.19, 95% CI -11.32 to -5.06, p

Primary surgical management is successful as the sole therapeutic modality in the majority of women with early-stage cervical, vaginal and vulvar cancer, but the presence of certain risk factors in the surgico-pathological specimen indicates a poorer prognosis. Adjuvant treatment can improve overall survival in such cases. Important risk factors in cervical cancer include intermediate-risk factors (large tumor size, deep cervical stromal invasion, lymph-vascular space invasion) and high-risk factors (positive or close margins, lymph nodes, or parametrial involvement). In vulvar cancer, positive margins and lymph nodes are the two most important factors for adjuvant therapy. Radiation therapy has been the mainstay of adjuvant therapy in these cancers, supplemented by chemotherapy. Recent advances have witnessed the inclusion of newer therapeutic modalities such as immunotherapy. This review addresses the current status of various adjuvant therapeutic modalities for these gynecological cancers.

Introduction The objectives of our study were to identify factors contributing to false-negative Papanicolaou (Pap) tests in patients with endocervical adenocarcinoma (EA) or adenocarcinoma in situ (AIS), and to analyze the impact of educational instruction on interobserver agreement in these cases. Materials and methods False-negative Pap tests from patients with EA/AIS were reviewed by a consensus group and by 12 individual reviewers in 2 rounds, with an educational session on glandular neoplasia in Pap tests conducted between the 2 rounds. Results Of 79 Pap tests from patients with EA/AIS, 57 (72.2%) were diagnosed as abnormal and 22 (27.8%) as negative. Of the 22 false-negative cases, 10 remained negative on consensus review, with false-negative diagnoses attributed to sampling variance. The other 12 cases were upgraded to epithelial abnormalities (including 8 to glandular lesions). The false-negative diagnoses were attributed to screening variance in 2 cases and interpretive variance in 10 cases. On individual review, abnormal cells were misinterpreted as reactive glandular cells or endometrial cells in 7 of 8 and 5 of 8 cases upgraded to glandular abnormalities, respectively. With education, the proportion of individual reviewers demonstrating at least moderate agreement with the consensus diagnosis (Cohen’s kappa >0.4) increased from 33% (4 of 12) to 75% (9 of 12). Conclusions Sampling and interpretive variance each accounted for nearly one-half of the false-negative Pap tests, with underclassification as reactive glandular or endometrial cells the main source of the interpretive variances. Educational instruction significantly decreased the interpretive variance and interobserver variability in the diagnosis of glandular abnormalities.

The study aimed to compare the performance of human papillomavirus (HPV)-based strategies to cytology for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in routine program in China. The study included 50,434 women ages 30–64 years from January 2015 to December 2019, to assess four strategies: cytology with HPV triage (strategy 1), primary HPV testing with reflex cytology (strategy 2), primary HPV testing with HPV-16/18 genotyping and reflex cytology for non-16–18 high-risk HPV genotypes (strategy 3), and co-testing (strategy 4). The main outcomes were sensitivity for CIN3+ and colposcopy referral rate. Overall, the rates of HPV positivity and cytologic abnormality were 7.0% [95% confidential interval (CI), 6.8–7.2] and 3.5% (95% CI, 3.3–3.6], respectively. The sensitivity for CIN3+ were 88.5% for strategy 4, 83.2% for strategy 3, 64.6% for strategy 1, and 60.1% for strategy 2. The relative sensitivity of strategy 4 and strategy 3 compared with strategy 1 for detecting CIN3+ were 1.38 (95% CI, 1.24–1.54) and 1.29 (95% CI, 1.14–1.46), respectively. The colposcopy referral rates of strategies 4 and 3 were significantly higher than that of strategy 1 (2.4% and 2.2% vs. 1.4%, P < 0.001). In conclusion, co-testing and primary HPV testing with HPV-16/18 genotyping and reflex cytology improved the sensitivity for CIN3+ compared with cytology but increased the colposcopy referral rate. Long-term negative predicted value for HPV-negative women should be studied to determine the screening interval. Our study provides further evidence to the introduction of HPV-based strategies in China. Prevention Relevance: Both co-testing and primary HPV testing with HPV-16/18 genotyping and reflex cytology triage provided higher sensitivity for detecting CIN3+; however, the number of colposcopy referrals also increased compared with cytology in a routine program. It has great public health implications for the introduction of HPV-based screening strategies in China.

Background Cervical cancer, caused by human papillomavirus infection, is the source of significant personal and societal burden, and robs more than one hundred thousand Indian women and their families of the chances of a healthy and productive life each year. As outlined by the World Health Organization, the three-pronged approach of screening, vaccination, and reduction in mortality by early treatment presents the possibility of the elimination of cervical cancer as a public health problem in the next decade. 1 Unfortunately, these approaches are all associated with significant barriers in India. Objectives Given that the main mandate of palliative care practitioners to prevent and relieve suffering, here we make the case for these practitioners to offer education around vaccination and screening to female relatives of women encountered with cervical cancer. Conclusion Offering prevention strategies for human papillomavirus aligns with the idea of preventing suffering and is within the scope of palliative care clinicians.

Although advancements in cervical cancer prevention have helped reduce the incidence, mortality, and prevalence, access to these preventive services has not been experienced equally by all women in the United States. The purpose of this study was to learn about the factors that affect access to preventive services in a low-income, primarily Black community. Using a community-based participatory research approach, women were recruited to participate in 7 focus groups, with 6 to 8 women per group (N = 45). Participants were mainly Black (64%), with a mean age of 46 years, and 60% reporting completing at least some college. The discussions were transcribed, and text data were organized using Dedoose software. Guided by qualitative content analysis, the data were analyzed through an iterative process of coding and condensing the codes into themes. Ten types of barriers and 11 facilitators relating to cervical cancer screening access were identified and grouped into 7 themes. Participants provided suggestions for promoting cervical cancer screening in their community. On the basis of the findings of the data, the researchers conceptualized and mapped culturally and geographically appropriate interventions to promote cervical cancer screening within the community of interest.

International audience; Objectives: To compare oncologic outcomes of patients with early-stage cervical cancer and negative nodes who underwent sentinel lymph node biopsy alone (SLNB) versus pelvic lymphadenectomy (PL).Methods: An ancillary analysis of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) was conducted. Only patients with early-stage cervical cancer (IA to IIA FIGO stage), bilateral detection of SLN, negative SLN after ultrastaging and negative non-SLN after final pathologic examination were included. Risk-factors of recurrence and disease-specific mortality were determined by Cox proportional hazard models.Results: Between January 2005 and July 2012, 259 node-negative patients were analyzed: 87 in the SLNB group and 172 in the PL group. The median follow-up was 47 months [4-127]. During the follow-up, 21 patients (8.1%) experienced recurrences, including 4 nodal recurrences (1.9%), and 9 patients (3.5%) died of cervical cancer. Disease-free survival (DFS) and disease-specific survival (DSS) were similar between SLNB and PL groups, 85.1% vs. 80.4%, p = 0.24 and 90.8% vs. 97.2%, p = 0.22 respectively. By Cox multivariate analysis, SLNB compared to PL was not associated with DFS (HR = 1.78, 95%CI = [0.71-4.46], p = 0.22) neither with DSS (HR = 3.02, 95%CI = [0.69-13.18], p = 0.14). Only pathologic risk level according to the Sedlis criteria was an independent predictor of DFS and DSS.Conclusions: Omitting full pelvic lymphadenectomy for patients with bilateral negative SLN does not seem to be associated with an increased risk of recurrence in this series. Survival non-inferiority needs to be confirmed by prospective trials.

PURPOSE The Radiation Oncology Alternative Payment Model (RO Model) will test prospective radiotherapy episode-based payments for 16 common disease sites. We created an automated analytics platform to calculate the impact of the RO Model vs historical fee-for-service episode reimbursements for brachytherapy treatments within five community oncology practices for prostate, uterine, and cervical cancer. METHODS AND MATERIALS Claims data between January 1, 2017 and October 2, 2019 for prostate, uterine, and cervical cancer were analyzed as per the RO Model Final Rule methodology. Expected professional and technical component (PC and TC) reimbursements were compared for episodes that utilized brachytherapy alone vs combination modality (external beam and brachytherapy) in the RO Model vs historical reimbursements. RESULTS 6,022 RO Model-defined episodes (60% prostate, 28% uterine, 13% cervical) were generated. Brachytherapy monotherapy episodes (14%) would have an average positive reimbursement in the RO Model (+$2,163 for prostate, +$711 for uterine, +$533 for cervical for the PC; +$12,168 for prostate, +$8,181 for uterine, +$11,322 for cervical for the TC), while combination modality episodes (15%) would have an average negative reimbursement in the RO Model (-$183 for prostate, -$1,701 for uterine, -$2,195 for cervical for the PC; -$374 for prostate, -$5,026 for uterine, -$2,801 for cervical for the TC). CONCLUSIONS Brachytherapy monotherapy episodes for prostate, uterine, and cervical cancer will benefit from an increase in payment, whereas combination modality episodes will receive lower reimbursement. Large shifts in episodic payment may be related to practice-wide adjustments and pricing based on partial episodes of care that may ultimately limit access to care for vulnerable patient populations with cancer.

Background This study aimed to validate the performance of the Korean Gynecologic Oncologic Group (KGOG)-1024 risk model in predicting the risk of distant failure after chemoradiation in patients with locally advanced cervical cancer (LACC). Methods In a retrospective cohort of 297 patients who received concurrent chemoradiation for advanced cervical cancer, individual risk was calculated using the KGOG-1024 risk model. The cohort was categorized into three risk groups (low-, intermediate-, and high-risk groups) according to the calculated risk. The means of the calculated and observed risks were compared within each group. Results The study population was classified into low-, intermediate-, and high-risk groups according to the KGOG-1024 risk model (27.2%, 49.3%, and 23.5% of patients, respectively). The calculated and observed 5-year cumulative incidence rates were 12.4% vs. 16.4% in the low-risk group, 23.2% vs. 25.9% in the intermediate-risk group, and 50.7% vs. 36.3% in the high-risk group. Overall, the calculated and observed risk was 26.7% vs. 25.6%. Conclusions The KGOG-1024 risk assessment model accurately predicted distant recurrence after chemoradiation in patients with LACC, especially in the low- and intermediate-risk groups. The model may be helpful for identifying patients for future trials assessing the possible benefit of adjuvant systemic treatment after chemoradiation.

PurposeTo test effects of positron emission tomography (PET)-based bone marrow-sparing (BMS) image-guided intensity modulated radiation therapy (IG-IMRT) on efficacy and toxicity for patients with locoregionally advanced cervical cancer.Methods and materialsIn an international phase II/III trial, patients with stage IB-IVA cervical carcinoma were treated with either PET-based BMS-IG-IMRT (PET-BMS-IMRT group) or standard image-guided IMRT (IMRT group), with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy. The phase II component nonrandomly assigned patients to PET-BMS-IMRT or standard IMRT. The phase III trial randomized patients to PET-BMS-IMRT versus IMRT, with a primary endpoint of progression-free survival (PFS) but was closed early for futility. Phase III patients were analyzed separately and in combination with phase II patients, comparing acute hematologic toxicity, cisplatin delivery, PFS, overall survival (OS), and patterns of failure. In a post-hoc exploratory analysis, we investigated the association between pretreatment absolute lymphocyte count (ALC) and OS.ResultsIn total, 101 patients were enrolled on the phase II/III trial, including 29 enrolled in phase III (PET-BMS-IMRT group: 16; IMRT group: 13) before early closure. Median follow-up was 33 months for phase III patients and 39 months for all patients. PFS and OS at 5 years for all patients were 73.6% (95% confidence interval [CI], 64.9%-84.3%) and 84% (95% CI, 76%-92.9%]), respectively. There were no differences in number of cisplatin cycles, OS, PFS, or patterns of failure between groups for the combined cohort. The incidence of acute grade ≥ 3 neutropenia was significantly lower in the PET-BMS-IMRT group compared with IMRT for randomized patients (19% vs 54%, χ2P=.048) and in the combined cohort (13% vs 35%, χ2P=.01). Patients with pretreatment ALC ≤ 1.5 k/µL had nonsignificantly worse OS on multivariable analysis (HR 2.85; 95% CI, 0.94-8.62; adjusted P=.216), compared with patients with ALC > 1.5 k/µL. There was no difference in posttreatment ALC by treatment group.ConclusionsPET-BMS-IMRT significantly reduced acute grade ≥3 neutropenia, but not treatment-related lymphopenia, compared with standard IMRT. We found no evidence that PET-BMS-IMRT affected chemotherapy delivery or long-term outcomes, and weak evidence of an association between pretreatment ALC and OS.

Summary Objective Recent studies have shown that minimally invasive surgery (MIS) is associated with a higher recurrence rate in patients with early-stage cervical cancer. In this study, we aim to report the survival outcomes of patients with early-stage cervical cancer who received MIS, performed in a single center by the same surgeon. Methods Eligible participants included patients with early-stage cervical cancer in stage IA1 with lymphovascular space invasion (LVSI+), IA2, and IB1. The surgeries were carried out by a single surgeon and survival outcomes of the 137 patients were evaluated retrospectively. Results The median follow-up time for the 137 patients was 53 (25–94) months, with the five-year disease-free survival (DFS) rate of 96.4% and the five-year overall survival (OS) rate of 96.8%. Among them, six (4.38%) patients relapsed and four (2.92%) of whom died. The five-year DFS rate was significantly higher in patients with tumor≤2 cm in size than in those with tumor >2 cm (P = 0.013), however, with no significant difference in the five-year OS rate (P = 0.219). Conclusion According to the existing literature and the results of this study, for MIS, the proficiency levels of a surgeon may be associated with survival outcomes of cancer patients. Tumor size may also be an important factor affecting survival outcomes of cervical cancer patients.

Summary We conducted a critical appraisal of published Phase 2 and 3 efficacy trials in relation to the prevention of cervical cancer in women. Our analysis shows the trials themselves generated significant uncertainties undermining claims of efficacy in these data. There were 12 randomised control trials (RCTs) of Cervarix and Gardasil. The trial populations did not reflect vaccination target groups due to differences in age and restrictive trial inclusion criteria. The use of composite and distant surrogate outcomes makes it impossible to determine effects on clinically significant outcomes. It is still uncertain whether human papillomavirus (HPV) vaccination prevents cervical cancer as trials were not designed to detect this outcome, which takes decades to develop. Although there is evidence that vaccination prevents cervical intraepithelial neoplasia grade 1 (CIN1) this is not a clinically important outcome (no treatment is given). Trials used composite surrogate outcomes which included CIN1. High efficacy against CIN1+ (CIN1, 2, 3 and adenocarcinoma in situ (AIS)) does not necessarily mean high efficacy against CIN3+ (CIN3 and AIS), which occurs much less frequently. There are too few data to clearly conclude that HPV vaccine prevents CIN3+. CIN in general is likely to have been overdiagnosed in the trials because cervical cytology was conducted at intervals of 6–12 months rather than at the normal screening interval of 36 months. This means that the trials may have overestimated the efficacy of the vaccine as some of the lesions would have regressed spontaneously. Many trials diagnosed persistent infection on the basis of frequent testing at short intervals, i.e. less than six months. There is uncertainty as to whether detected infections would clear or persist and lead to cervical changes.

Pelvic organ prolapse and carcinoma of the cervix are common entities but their association is rare. In more than 60% of the cases, the uterine prolapse is present for at least 10 years.[1][1] The displacement of the uterine cervix from the natural environment of the vagina is thought to explain a

This phase II randomized clinical trial aimed to assess the efficacy and toxicity of Endostar, an antiangiogenesis inhibitor, combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Patients with LACC were randomly assigned to either CCRT plus Endostar (CCRT+E arm) or CCRT alone (CCRT arm). All patients received pelvic intensity-modulated radiation therapy (IMRT) and brachytherapy. Weekly cisplatin was administered concurrently with IMRT. Patients in the CCRT+E arm also received concurrent Endostar every 3 weeks for two cycles. The primary endpoint was progression-free survival (PFS) and acute toxicities. The exploratory endpoint was the impact of vascular endothelial growth factor receptor-2 (VEGFR2) expression on long-term survival. A total of 116 patients were enrolled. Patients in the CCRT+E arm and in the CCRT arm had similar acute and late toxicity profile. The 1- and 2-year PFS were 91.4% versus 82.1% and 80.8% versus 63.5% (p=0.091), respectively. The 1- and 2-year distance metastasis-free survival (DMFS) were 92.7% versus 81.1% and 86.0% versus 65.1% (p=0.031), respectively. Patients with positive VEGFR2 expression had significant longer PFS and overall survival (OS) compared with those with negative VEGFR2 expression. Patients in the CCRT+E arm had significantly longer PFS, OS, and DMFS than those in the CCRT arm when VEGFR2 expression was positive. In conclusion, CCRT plus Endostar significantly improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival for patients with positive VEGFR2 expression.

Implementation of quality control measures ensures acceptable performance by a laboratory. This study aims to assess the quality of cervical cytopathology reporting using quality metrics like atypical squamous cells (which include both atypical squamous cells of undetermined significance and atypical squamous cell -cannot rule out high grade squamous intraepithelial lesion)/squamous intraepithelial lesion (ASC/SIL), cytohistological correlation (CHC) and positive predictive value (PPV) of Papanicolaou (Pap) smears for squamous lesions of cervix.A retrospective study of Pap smears from 2015 to 2020 was performed. The quality metrics analysed include diagnoses of ASCUS, ASC-H and ASCUS/SIL ratio, CHC and PPV. Cases with cervical biopsies/hysterectomy were included for CHC, and discrepancy was defined as discordance in diagnostic category between cytology and histology in the CHC.A total of 22,695 cervical cytology smears were reported. Unsatisfactory smears (n = 290) were excluded. Squamous lesions were reported in 233 smears, and the Bethesda system of nomenclature was followed. A definitive diagnosis (SILs and SCC) was given in 74% of cases. ASCUS and ASC-H were reported in 47 and 14 cases, respectively. The most common lesion on Pap smear was high-grade squamous intraepithelial lesion (HSIL; n = 92), followed by low-grade squamous intraepithelial lesion (LSIL; n = 64), and two were ungradable SIL. Squamous cell carcinoma (SCC) was reported in 14 smears. The ASC/SIL ratio was 0.38. CHC (n = 139) was 100% for ASC-H, LSIL, SCC and 84.7% for HSIL. A review of discrepant cases suggested sampling and interpretational discrepancy in five and one cases, respectively. The PPV of Pap smear for squamous lesions was 96.4%.It is essential to have good quality cytopathology reports for early identification, which enables appropriate management. The most commonly used quality indicator for cytopathology is the ASCUS/SIL ratio. This study suggests the inclusion of the CHC and PPV values as quality metrics for Pap smear, since these are easily measurable and serve as a good indicator of quality in cervical cytopathology reporting.

Human papillomavirus genotypes (HPVs) have been confirmed to be the major cause of cervical intraepithelial neoplasia (CIN) that remains to be one of the most common women cancers around the world. It seems other risk factors have synergistic effects on cervical cancer occurrence including smoking, dietary pattern, sexual behavior, ethnicity, epigenetics, and environmental hazardous materials. Our study characterized the potential cancerous role of lead (Pb) as a common toxic environmental pollutant agent on CIN outcomes. Lead concentration was quantified using an atomic absorption spectrometer in liquid-based cytology specimens of 40 CIN-HPV positive subjects, 50 HPV infected non-cancerous cases, and 43 non-HPV infected/non-cancerous women. Pb concentration was 5.5 (4.7–6.4) μg/dL, 4.7 (4.2–8.7) μg/dL, and 4.7 (4.5–5.4) μg/dL in the CIN-HPV positive group, HPV infected non-cancerous cases, and non-HPV infected/non-cancerous group, respectively. The results showed higher Pb concentration is associated with higher risk for cervical malignancy in comparison with non-HPV infected/non-cancerous subjects, after controlling for age effect (aOR = 4.55, 95% CI: 1.55–15.07, P < 0.01). Our finding suggested a direct significant association between Pb accumulation and CIN existence. The consequences need to be further validated by including more relevant risk factors and controlling the confounders for better understating of Pb impact from outdoor air pollution on cervical cancer progression.

Purpose Tumor mutational burden (TMB) is a surrogate biomarker of neo-antigens and high TMB status is associated with favorable response to immune-checkpoint inhibitors (ICIs). This study aimed to elucidate the association between TMB and the outcome of definitive radiotherapy in patients with cervical cancer. Materials and methods TMB and treatment outcome were retrospectively analyzed in patients with newly diagnosed cervical cancer treated with definitive radiotherapy available with somatic mutation data of pre-treatment tumors obtained using a commercially available gene panel. Results The study enrolled 98 patients (median follow-up period, 61 months). The median TMB was 9.5 mutations per megabase (range, 3.0–35.5 mutations per megabase). After dichotomization based on this median value, the 5-year overall survival (OS) for TMB-high patients was significantly worse than that of TMB-low patients (61.1% vs. 82.2%). Multivariate analysis identified high TMB status as a significant prognostic factor for worse OS, along with advanced stage, para-aortic lymph node involvement, and absence of concurrent chemotherapy. Conclusion These data indicate that TMB is a potential prognostic factor for worse survival in patients with cervical cancer treated with definitive radiotherapy, thereby providing a rationale for treatment of TMB-high cervical cancers with a combination of ICIs plus radiotherapy. Secondary abstract This retrospective study of 98 patients demonstrates for the first time that tumor mutational burden (TMB) is an independent prognostic factor for worse overall survival of patients treated with definitive radiotherapy, providing a rationale for treatment of TMB-high cervical cancers with a combination of immune-checkpoint inhibitors plus radiotherapy.

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.

An unacceptable number of women continue to die from cervical cancer around the world each year. Despite established primary and secondary prevention measures, and a natural history of disease which provides a long latent phase in which to intervene, there are still more than 500,000 women diagnosed with cervical cancer globally each year, and 300,000 related deaths. Approximately 90% of these cervical cancer cases and deaths occur in low- and middle-income countries (LMIC). The World Health Organization (WHO) recently launched a Global Strategy to Accelerate the Elimination of Cervical Cancer that outlines 3 key steps: (i) vaccination against human papillomavirus (HPV); (ii) cervical screening; and (iii) treatment of precancerous lesions and management of invasive cancer. Successful implementation of all 3 steps could reduce more than 40% of new cervical cancer cases and 5 million related deaths by 2050. However, this initiative requires high level commitment to HPV immunization programs, innovative approaches to screening, and strengthening of health systems to provide treatment for both precancerous lesions as well as invasive cervical cancer.

Metabolic reprogramming is a common feature of tumor cells and is associated with tumorigenesis and progression. In this study, a metabolic gene-associated prognostic model (MGPM) was constructed using multiple bioinformatics analysis methods in cervical carcinoma (CC) tissues from The Cancer Genome Atlas (TCGA) database, which comprised fifteen differentially expressed metabolic genes (DEMGs). Patients were divided into a high-risk group with shorter overall survival (OS) and a low-risk group with better survival. Receiver operating characteristic (ROC) curve analysis showed that the MGPM precisely predicted the 1-, 3- and 5-year survival of CC patients. As expected, MGPM exhibited a favorable prognostic significance in the training and testing datasets of TCGA. And the clinicopathological parameters including stage, tumor (T) and metastasis (M) classifications had significant differences in low- and high-risk groups, which further demonstrated the MGPM had a favorite prognostic prediction ability. Additionally, patients with low-ESTMATEScore had a shorter OS and when those combined with high-risk scores presented a worse prognosis. Through “CIBERSORT” package and Wilcoxon rank-sum test, patients in the high-risk group with a poor prognosis showed lower levels of infiltration of T cell CD8 (P < 0.001), T cells memory activated (P = 0.010) and mast cells resting (P < 0.001), and higher levels of mast cells activated (P < 0.001), and we also found these patients had a worse response for immunosuppressive therapy. These findings demonstrate that MGPM accurately predicts survival outcomes in CC patients, which will be helpful for further optimizing immunotherapies for cancer by reprogramming its cell metabolism.

Background Inflammation is emerging as a potential mechanism of cervical carcinogenesis. However, few studies have investigated the association between host inflammatory status and the natural course of cervical precursor lesion. The aim of this study was to assess the probability of LSIL regression, associated with an inflammatory biomarker, high-sensitivity C-reactive protein (hs-CRP). Methods In a longitudinal cohort study, female participants were examined annually or biannually using cervical cytology between 2006 and 2015. Incident LSIL cases were included in the analysis, with regression defined as at least one consecutive normal cytologic result. A total of 520 women aged 22-64 years were followed up for LSIL regression. The multivariable-adjusted hazard ratios (HRs) for LSIL regression were estimated using a parametric proportional hazards model. Results During 827.5 person-years of follow-up, 486 out of 520 subjects (93.5%) showed LSIL regression. After adjusting several important potential confounders, a higher quartile of hs-CRP levels was significantly associated with a lower rate of regression (for quartile 4 vs quartile 1, inverse HR 1.33; 95% CI, 1.04-1.69; P for trend = 0.028). Conclusions The low rate of spontaneous regression recorded in women with higher hs-CRP lends support to the role of the perturbated host inflammatory status in cervical carcinogenesis, and suggests that hs-CRP level could help monitor LSIL.

Gynecologic cancers contribute to a significant portion of cancer morbidity and mortality among women in the United States and across the globe. This article provides a comprehensive review of current screening guidelines and novel techniques that have promise in the prevention and early detection of gynecologic cancers in the future. The authors anticipate a move toward less invasive testing modalities, use of cancer biomarkers, and the prevention and treatment of high-risk factors such as human papilloma virus infection and obesity.

Objective To evaluate the prognostic and predictive significance of lymphovascular invasion (LVI) and lymph node metastasis of intratumoral budding (ITB) and its correlation with clinicopathological parameters in patients with cervical cancer. Methods Total 151 patients with cervical cancer who underwent radical hysterectomy with pelvic and/or paraaortic lymphadenectomy were included. We assessed the status of ITB and peritumoral budding (PTB) in all available hematoxylin and eosin-stained specimens. Univariate and multivariate analyses were performed for ITB, PTB, and other clincopathological parameters as predictors of recurrence. Results ITBhigh (≥3TB/HPF) was significantly associated with large tumor size, deep stromal invasion, LVI, parametrial invasion, and lymph node metastasis. The numbers of ITBs and PTBs were positively correlated (r2 = 0.754, p Conclusion ITBhigh is an independent prognostic factor for tumor recurrence. ITB is a surrogate marker for predicting LVI in cervical cancers. The evaluation of ITB may be readily applied in the clinical setting for improved prognosis and to guide the clinical management of patients with cervical cancer.

Background Cervical cancer is the fourth most common cancer in the world, affecting mainly women residing in low- and middle-income countries. Progression from a pre-invasive phase to that of an invasive phase generally takes years and provides a window of opportunity to screen for and treat precancerous lesions. Methods This study is being conducted at four sites in north Karnataka, India. Community sensitization activities have been organized in the study areas to create awareness among stakeholders, including elected representatives, physicians, health care workers, and potential participants. Organized community based as well as hospital-based screening is being conducted using visual inspection with acetic acid (VIA). Screen positive women are referred to respective study hospitals for colposcopy and directed biopsy. Participants with confirmed high-grade cervical dysplasia (high-grade squamous intraepithelial lesions or HSIL) who fit all other eligibility criteria will be recruited to the study and will receive cryotherapy using CryoPop®, an innovative new cryotherapy device. Discussion There is a need to develop an inexpensive, simple, and effective cryotherapy device for use by frontline health care providers at locations where screening and timely treatment can be given, accelerating access to cervical cancer prevention services and minimizing loss to follow-up of women with precancerous lesions who need treatment. Trial registration Clinical Trial Registry - India CTRI/2019/01/017289 ClinicalTrials.Gov number NCT04154644. Registered on November 6, 2019.

PURPOSE We assessed the impact of mHealth on Pap test screening uptake and also determined the factors that affect screening uptake among women in Lagos, Nigeria. MATERIALS AND METHODS A randomized controlled trial was carried out among women in two tertiary health institutions in Lagos, Nigeria, between July 2020 and March 2021. Participants were randomly assigned to either a text message (mHealth) intervention or usual care arm. The main study outcome was the uptake of Pap smear testing within 6 months of enrollment in the study. We tested the associations between two groups of continuous variables using the unpooled independent-sample t-test (normal distribution) and that of two groups of categorical variables with the chi-square (χ2) test. Using a multinomial logistic regression model, we adjusted for relevant sociodemographic and clinical predictors of uptake of Pap smear screening. Statistical significance was defined as P < .05. RESULTS There was a significantly higher rate of uptake of Pap smear screening among women in the mHealth arm compared with those in the usual care arm (51.0% v 35.7%, P = .031). Following adjustment in the final multivariate model, level of income (odds ratio [OR] = 5.13, 95% CI, 1.55 to 16.95), awareness of Pap smear (OR = 16.26; 95% CI, 2.49 to 76.64), General Outpatient clinic attendance, and introduction of mHealth intervention during follow-up (OR = 4.36; 95% CI, 1.44 to 13.22) were the independent predictors of Pap smear uptake. CONCLUSION The use of mHealth technologies intervention via short-text message services is a feasible solution for cervical cancer prevention in low- and middle-income countries, and thus, the widespread use of mHealth services by health care providers and policymakers could contribute to the implementation of cervical cancer prevention services in Nigeria and in the settings of other low- and middle-income countries.

PURPOSE Major improvements have occurred in access to invasive cervical cancer (ICC) screening in HIV-infected women over the past decade in sub-Saharan Africa. However, there is limited information on changes in the burden of HIV-related ICC at a population level. Our objective was to compare HIV-related ICC over a decade and document factors associated with HIV infection in women with ICC in Côte d'Ivoire. METHODS A repeated cross-sectional study was conducted in referral hospitals of Abidjan, Côte d'Ivoire, through the 2009-2011 and 2018-2020 periods. Women diagnosed with ICC were systematically tested for HIV. Demographics, ICC risk factors, cancer stage (International Federation of Gynecology and Obstetrics), and HIV characteristics were collected through questionnaires. Characteristics of HIV-related ICC were compared between the periods, and factors associated with HIV in women diagnosed with ICC in 2018-2020 were documented through a multivariable logistic model. RESULTS During the 2009-2011 and 2018-2020 periods, 147 and 297 women with ICC were diagnosed with estimated HIV prevalence of 24.5% and 21.9% ( P = .53), respectively. In HIV-infected women, access to antiretroviral treatment increased from 2.8% to 73.8% ( P < 10−4) and median CD4 cell count from 285 (IQR, 250-441) to 492 (IQR, 377-833) cells/mm3 ( P = .03). In women diagnosed with ICC during the 2018-2020 period, HIV infection was associated with a less advanced clinical stage (International Federation of Gynecology and Obstetrics I or II stage) (adjusted OR, 2.2 [95% CI, 1.1 to 4.4]) and with ICC diagnosis through a systematic screening (adjusted OR, 10.5 [95% CI, 2.5 to 45.5]). CONCLUSION Despite a persistently high proportion of HIV-related ICC over time in Côte d'Ivoire, HIV was associated with less advanced clinical stage at ICC diagnosis. Recent improvements in ICC screening services across HIV clinics might explain this association and support their implementation across non-HIV health facilities.

Cervical cancer is the leading cause of death among women in Nepal. The American Society of Clinical Oncology (ASCO) and The University of Texas MD Anderson Cancer Center collaborated with international and local experts to hold a cervical cancer prevention course in Nepal in November 2019. The course included didactic lectures and a hands-on workshop. The didactic lectures included the epidemiology of cervical cancer globally and locally, cervical cancer screening guidelines, human papillomavirus vaccination, colposcopy and visual inspection with acetic acid (VIA), cervical dysplasia, and cervical cancer treatment. The hands-on workshop consisted of four stations: (1) VIA; (2) colposcopy, cervical biopsy, and endocervical curettage; (3) thermal ablation; and (4) loop electrosurgical excision procedure (LEEP). A train-the-trainer model short course was held by the international faculty to assist six local faculty to become familiar with the instruments, procedures, and models used in the hands-on training stations. Forty-two people (84% gynecologist, 8% radiation oncologist, and 8% other) attended the course. Following the course, the international faculty visited the regional hospitals for additional educational activities. Increased knowledge in cervical cancer screening guidelines and ability in performing VIA, colposcopy and cervical biopsy, thermal ablation, and LEEP were reported by 89%, 84%, 84%, 87%, and 84% of participants, respectively, from the postcourse on-site evaluations. From the 6-month follow-up survey, all respondents reported that they had made practice changes based on what they learned in the course and had implemented or tried to implement the cervical cancer screening guidelines presented at the course. In conclusion, the course evaluations suggested an improvement in participants' ability to perform cervical cancer screening and diagnostic procedures and reported the changes in practices after training.

Background Hepatitis B virus (HBV) infection has been associated with an increased risk of a few malignancies. However, the prognostic impact of HBV infection remains unclear in cervical cancer. Objective To explore the association between HBV infection and survival outcomes of patients with primary cervical cancer, using overall survival (OS) and disease‐free survival (DFS) as primary endpoints. Methods This analysis was performed retrospectively with newly diagnosed cervical cancer patients admitted to the Department of Gynecologic Oncology at the Sun Yat‐sen Memorial Hospital of Sun Yat‐sen University from June 2013 to October 2019, who were enrolled and followed up. The Kaplan–Meier method and Cox proportional hazard analysis were used to examine the performance of HBV infection in predicting OS and DFS. Results Patients were followed up for a median of 37.17 months (95% CI, 34.69–39.65). Among the 695 patients, 87 (12.5%) were serologically positive for hepatitis B surface antigen (HBsAg), and 276 (39.7%) had a prior history of HBV infection. There was no significant difference between HBsAg‐positive group and HBsAg‐negative patients concerning OS or DFS. Multivariate analysis showed prior HBV infection was an independent favorable prognosticator for OS (HR, 0.335; 95% CI, 0.153–0.0.734; p = 0.006) and DFS (HR, 0.398; 95% CI, 0.208–0.691; p = 0.002). Conclusion We provide the first clinical evidence that suggests prior HBV infection as an independent favorable prognostic factor for patients with primary cervical cancer., Our study was based on a retrospective cohort study, to explore the association between HBV infection and survival outcomes of patients with primary cervical cancer, using overall survival (OS) and disease‐free survival (DFS) as main endpoints. In this study, we find HBsAg has no significance for the prognosis of cervical cancer, and provide the first clinical evidence that previous hepatitis B infection with cervical cancer as an positive effect on the prognosis as an independent favorable prognostic factor for patients with primary cervical cancer.