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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.

The persistent infection of high-risk Human papillomavirus (HR-HPV) induced cervical cancer remains a challenge in women worldwide including India. Recent advances in cancer research have paved the way for advanced cancer treatment modalities including immunotherapy by manipulating the function or number of cytotoxic T cells. It is well established that anaphylatoxins like C3a and C5a of complement system influence tumor growth by evading apoptosis leading to progression of cancer. The role of the complement system, particularly the complement regulatory proteins (CRPs) which are important determinants of immune response play a crucial role in carcinogenesis. In a tumor microenvironment (TME) assisted suppression of immune effector cells may be achieved through CRPs. However, recent advances in pharmacogenomics including drug designing and combination of these approaches have provided a holistic understanding of signaling pathways and their crosstalk, to regulate cellular communications.This review describes the role of complement system; particularly CRPs in HPV induced cervical carcinogenesis which may be used for designing anti- HPV or cervical cancer therapeutics.

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.

Purpose Differences in hysterectomy prevalence by rural or urban residence could distort comparisons of rural-urban cervical and uterine cancer incidence. Using data from a large population-based survey, we sought to understand whether hysterectomy prevalence varies by rural or urban residence and whether the relationship between hysterectomy prevalence and rurality varies by race or ethnicity. Methods Our analysis included 197,759 female respondents to the 2018 Behavioral Risk Factor Surveillance System, aged 20-79 years. We calculated population weighted proportions and 95% confidence intervals for hysterectomy prevalence, stratified by rural-urban residence and 5-year age groups. We also report estimates of hysterectomy prevalence by rural-urban residence for specific race and ethnic groups. Findings Hysterectomy prevalence increased with age and was more common among rural women than urban women. The largest absolute difference occurred among women aged 45-49 years; 28.6% of rural women (95% CI: 25.1-32.2) and 16.6% of urban women (95% CI: 15.3-17.8) reported a hysterectomy. For hysterectomy prevalence by race and ethnicity, rural estimates were higher than urban estimates for the following groups of women: non-Hispanic Asian, non-Hispanic other race, non-Hispanic Black, and non-Hispanic White. Among Hispanic women and non-Hispanic American Indian/Alaska Native women, rural-urban differences in hysterectomy prevalence were not statistically different at the 95% confidence level. Conclusions Our results suggest that variation in hysterectomy prevalence, if not adjusted in the analysis, could produce distorted comparisons in measures of the relationship between rurality and uterine and cervical cancer rates. The magnitude of this confounding bias may vary by race and ethnicity.

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.

Background: Demethylincisterol A3 (DTA3) has been identified as an SHP2 inhibitor and suppresses the growth of many cancer cells. 5-Fluorouracil (5-FU) is widely used for the clinical treatment of various cancers. However, the combination effects of 5-FU and DTA3 on cervical cancer cells remain unknown. Objective: This study evaluates the mechanism of the combination effects of 5-FU and DTA3 in cervical cancer cells. Methods: The synergistic cytotoxic effects of 5-FU and DTA3 in cervical cancer cells were calculated. Apoptosis was analysed by flow cytometry. Western blot analyses were used to examine the related signalling pathways. Results: DTA3 and 5-FU synergized to induce apoptosis and repress proliferation of cervical cancer cells by downregulating the activation of PI3K/AKT and NF-κB signalling pathways. We provided evidence that the upregulation of SHP2 expression by transfection significantly inhibited the cytotoxicity of 5-FU and DTA3. SHP2 knockdown enhanced the anti-proliferation activity of 5-FU, indicating targeting SHP2 sensitized cervical cancer cells to 5-FU. Conclusion: Our study demonstrates that SHP2 inhibitor DTA3 and 5-FU have a synergistic cytotoxic effect on cervical cancer cells. The synergistic combination of SHP2 inhibitor and 5-FU may present a promising strategy for the treatment of cervical cancer.

Accurate cervical lesion detection (CLD) methods using colposcopic images are highly demanded in computer-aided diagnosis (CAD) for automatic diagnosis of High-grade Squamous Intraepithelial Lesions (HSIL). However, compared to natural scene images, the specific characteristics of colposcopic images, such as low contrast, visual similarity, and ambiguous lesion boundaries, pose difficulties to accurately locating HSIL regions and also significantly impede the performance improvement of existing CLD approaches. To tackle these difficulties and better capture cervical lesions, we develop novel feature enhancing mechanisms from both global and local perspectives, and propose a new discriminative CLD framework, called CervixNet, with a Global Class Activation (GCA) module and a Local Bin Excitation (LBE) module. Specifically, the GCA module learns discriminative features by introducing an auxiliary classifier, and guides our model to focus on HSIL regions while ignoring noisy regions. It globally facilitates the feature extraction process and helps boost feature discriminability. Further, our LBE module excites lesion features in a local manner, and allows the lesion regions to be more fine-grained enhanced by explicitly modelling the inter-dependencies among bins of proposal feature. Extensive experiments on a number of 9888 clinical colposcopic images verify the superiority of our method (AP .75=20.45) over state-of-the-art models on four widely used metrics.

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: Acetowhite (AW) region is a critical physiological phenomenon of precancerous lesions of cervical cancer. An accurate segmentation of the AW region can provide a useful diagnostic tool for gynecologic oncologists in screening cervical cancers. Traditional approaches for the segmentation of AW regions relied heavily on manual or semi-automatic methods. OBJECTIVE: To automatically segment the AW regions from colposcope images. METHODS: First, the cervical region was extracted from the original colposcope images by k-means clustering algorithm. Second, a deep learning-based image semantic segmentation model named DeepLab V3+ was used to segment the AW region from the cervical image. RESULTS: The results showed that, compared to the fuzzy clustering segmentation algorithm and the level set segmentation algorithm, the new method proposed in this study achieved a mean Jaccard Index (JI) accuracy of 63.6% (improved by 27.9% and 27.5% respectively), a mean specificity of 94.9% (improved by 55.8% and 32.3% respectively) and a mean accuracy of 91.2% (improved by 38.6% and 26.4% respectively). A mean sensitivity of 78.2% was achieved by the proposed method, which was 17.4% and 10.1% lower respectively. Compared to the image semantic segmentation models U-Net and PSPNet, the proposed method yielded a higher mean JI accuracy, mean sensitivity and mean accuracy. CONCLUSION: The improved segmentation performance suggested that the proposed method may serve as a useful complimentary tool in screening cervical cancer.

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.

Uterocervical motions and organ filling during cervical cancer conformal radiotherapy is complex. This prospective, observational study investigated set-up margins (clinical target vo, ume [CTV] to planning target volume [PTV]) for pelvic nodal CTV and internal margin (CTV to internal target volume [ITV]) expansions for uterocervical movements during cervical cancer radiotherapy.During cervical cancer radiotherapy, a daily kilovoltage, cone-beam computed tomography (CBCT) scan was acquired. Bony anatomy-based rigid co-registration and matching to vessels/pelvic nodal region was carried out to document shifts, errors (systematic and random) and to calculate CTV to PTV margins. Subsequently, soft-tissue matching was carried out at the mid-cervical region and uterine fundus to record shifts, errors and to calculate CTV to ITV margins.In 67 patients, 1380 CBCT scans were analysed. The mean (±standard deviation) couch shifts for CTV pelvic nodal region in all directions were within 4.5-5.3 mm, systematic and random errors 3.0-3.6 mm and set-up margins of within 10 mm (except anterior margin 10.3 mm). For the mid-cervical region, mean shifts were 4.5-5.5 mm, systematic and random errors 2-4 mm amounting to10 mm internal margins (CTV-ITV for cervix) and for uterine fundus mean (±standard deviation) shifts were larger in the superior direction (12.1 mm) but 4.0-7.5 mm in other directions, systematic and random errors 2-7 mm amounting to anisotropic margins in various directions (10 mm in anterior-posterior and lateral directions, 12-20 mm in superior-inferior directions) (CTV-ITV for uterine fundus).Our study suggests anisotropic CTV to ITV and CTV to PTV margins for cervical cancer radiotherapy.

Background Zimbabwe has one of the highest incidence rates of cervical cancer in the world – 61.7 per 100,000 women. The government of Zimbabwe introduced bivalent HPV vaccine with a 0,12 month schedule to all 10–14 year old girls using a pulsed-campaign approach in May 2018 (dose 1) and May 2019 (dose 2). Methods In August 2019, we conducted a population-based, two-stage cluster survey of households with girls who were eligible for the national HPV vaccination program to determine two-dose HPV vaccination coverage in three districts of Zimbabwe. All households with girls currently aged 11 to 15 years were line-listed through a census conducted in the pre-selected clusters from each district prior to survey administration. A simple random sample of eligible households was selected from these lists to estimate HPV vaccine coverage at sufficient power with a margin of error of +/- 5%. Criteria for district selection included estimated vaccine uptake (low, medium, high), rural/urban/peri-urban, geographic area, estimated number of girls not in school, and recent natural disasters or disease outbreaks. We oversampled households with girls aged 13 or 14 years at the time of dose 1. Results On-time dose 1 uptake ranged from 88 to 94% and two-dose HPV vaccine coverage ranged from 75 to 86% across the three districts. Nearly all vaccinations occurred in schools, and less than 2% of girls did not attend school. There were challenges assessing ages of girls at schools prior to vaccination – 9% of girls vaccinated were less than 10 years old at time of dose 1. Discussion Zimbabwe has demonstrated that high uptake and successful completion of 2-dose HPV vaccination can be achieved with an annual dosing schedule. Efforts going forward will need to focus on minimizing dropout between doses and routinizing annual vaccinations in schools for every subsequent new cohort of eligible girls in the country.

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.

Purpose The aim of the study was to compare the dose to vaginal points between two intracavitary applicators used for HDR brachytherapy in Carcinoma Cervix METHODS AND MATERIALS: Patients reporting to our center for Carcinoma cervix intracavitary brachytherapy were randomly allocated to treatment with either Manchester or Fletcher Suit Delclos (FSD) applicator. All patients received an EBRT dose of 50 Gy in 25 fractions along with weekly Cisplatin (40 mg/m2). Brachytherapy was administered using CT based planning. All patients received a dose of 7 Gy to Point A one week apart for a total of three fractions. For vaginal dose reporting, the PIBS points (PIBS, PIBS+1, PIBS+2, PIBS-1, PIBS-2) and dose to vagina at the level of ovoids was compared between the two applicators RESULTS: A total of 30 Carcinoma cervix patients were randomly allocated to receive intracavitary brachytherapy with either Manchester or FSD applicator. The mean vaginal reference length for patients treated with Manchester applicator was 4.3 and for patients treated with FSD applicator was 4.4. On analyzing dose to different vaginal points, patients treated with Manchester applicator received significantly higher mean and median doses to all PIBS points (except PIBS-2 cm) as compared to FSD applicator. On analyzing dose to the upper vagina at the level of the ovoids, the Manchester applicator delivered higher antero-posterior doses as compared to FSD applicator. Conclusions Manchester applicator gives higher dose to the vagina as compared to FSD applicator for intracavitary brachytherapy in Carcinoma Cervix. The choice of using a particular applicator depends on the residual disease at the time of brachytherapy and patient anatomy.

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 prognosis for cervical cancer (CC) patients with lymph node metastasis (LNM) is extremely poor. Lipid droplets (LDs) have a pivotal role in promoting tumor metastasis. The crosstalk mechanism between LDs and LNM modulated in CC remains largely unknown.This study aimed to construct a miRNA-dependent progonostic model for CC patients and investigate whether miR-532-5p has a biological impact on LNM by regualting LDs accumulation.LASSO-Cox regression was applied to establish a prognostic prediction model. miR-532-5p had the lowest P-value in RNA expression (P 0.001) and prognostic prediction (P 0.0001) and was selected for further study. The functional role of the prognostic miR-532-5p-correlated competing endogenous RNA (ceRNA) network was investigated to clarify the crosstalk between LDs and LNM. The underlying mechanism was determined using site-directed mutagenesis, dual luciferase reporter assays, RNA immunoprecipitation assays, and rescue experiments. A xenograft LNM model was established to evaluate the effect of miR-532-5p and orlistat combination therapy on tumor growth and LNM.A novel 5-miRNAs prognostic signature was constructed to better predict the prognosis of CC patient. Further study demonstrated that miR-532-5p inhibited epithelial-mesenchymal transition and lymphangiogenesis by regulating LDs accumulation. Interestingly, we also found that LDs accumulation promoted cell metastasis in vitro. Mechanistically, we demonstrated a miR-532-5p-correlated ceRNA network in which LINC01410 was bound directly to miR-532-5p and effectively functioned as miR-532-5p sponge to disinhibit its target gene-fatty acid synthase (Our findings highlight a LD accumulation-dependent mechanism of miR-532-5p-modulated LNM and support treatment with miR-532-5p/orlistat as novel strategy for treating patients with LNM in CC.

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

Introduction Demonstrating human papillomavirus vaccine impact is critical for informing guidelines to increase vaccination and decrease human papillomavirus‒related outcomes, particularly in states with suboptimal vaccination coverage, such as Tennessee. This study examines the trends in high-grade cervical lesion incidence among Tennessee Medicaid-enrolled women aged 18–39 years and the subset of women who were screened for cervical cancer. Methods Using a validated claims-based model to identify incident cervical intraepithelial neoplasia Grades 2 or 3 or adenocarcinoma in situ events, annual age group‒specific incidence rates from Tennessee Medicaid billing data, 2008–2018, were calculated. Significant trends were determined by Joinpoint. Analyses were conducted in 2020. Results From 2008 to 2018, high-grade cervical lesion incidence significantly declined in women aged 18–20 years (average annual percentage change= −31.9, 95% CI= −38.6, −24.6), 21–24 years (average annual percentage change= −12.9, 95% CI= −22.3, −2.4), and 25–29 years (average annual percentage change= −6.4, 95% CI= −8.1, −4.6). Among screened women, rates significantly declined for ages 18–20 years (average annual percentage change= −20.3, 95% CI= −25.3, −15.0), 21–24 years (average annual percentage change= −10.2, 95% CI= −12.6, −7.8), and 25–29 years (average annual percentage change= −2.6, 95% CI= −3.9, −1.2). Trends from 2008 to 2018 were stable for older age groups (30–34 and 35–39 years). Conclusions Results show reductions in high-grade cervical lesion incidence among ages most likely to have benefited from the human papillomavirus vaccine. Declines among young, screened women suggest causes other than reduction in screening. Evidence of vaccine impact in populations with low-vaccination coverage, such as Tennessee, is promising.

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.

Following successful school-based demonstration programs in 2014-2016, the human papillomavirus (HPV) vaccine was introduced nationwide in Senegal for 9-year-old girls in 2018, using a routine service delivery strategy at health facilities, schools, and other outreach sites. We reviewed the HPV vaccine introduction in Senegal to understand the successes, challenges, and lessons learned. Focusing on three key domains (program decision-making, planning, and implementation), we conducted ten semi-structured interviews during 2019-2020 with purposively selected national-level stakeholders (government, expert advisory committee, key technical and implementation partners) and comprehensive desk reviews of country documents on HPV vaccine introduction. Due to the global HPV vaccine shortage, the introduction was limited to a single-age cohort; therefore, 9-year-old girls were chosen. This strategy enabled Senegal to potentially reach more girls in primary education because school enrolment rates decline thereafter. Vaccination through routine delivery platforms (i.e., health facility, school-based, and community outreach) was perceived to be more cost-effective than a campaign approach. High-level political commitment and collaborations between immunization and education partners were frequently cited by key informants as reasons for a successful vaccine introduction. All key informants reported that the health care worker (HCW) strike, rumors, and vaccine hesitancy negatively impacted the introduction. Other challenges noted included insufficient information on attitudes towards HPV vaccination among HCWs, teachers, and community members. Senegal successfully introduced HPV vaccine into the national immunization schedule, using a routine delivery strategy. Strong leadership and a multi-sectoral approach likely contributed to this success. To build sustainability of the HPV vaccination program in the future, it is important to improve the understanding and engagement among all stakeholders, including HCWs and community members, and to strengthen and innovate communication and crisis management strategies. To better understand the efficiency and effectiveness of Senegal's vaccination strategy, additional assessments of the operational costs and coverage achieved are needed.

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.

Interstitial and intracavitary gynecological HDR brachytherapy involve precise, localized delivery to targets with high dose gradients, sparing adjacent organs at risk (OAR). Due to the proximity of the rectum, bowel and bladder to the target, deviations in the applicator or catheter with respect to patient anatomy can significantly increase dose to OAR. The magnitude and direction of applicator and catheter migration at each fraction was assessed for template interstitial and tandem and ring (TR) cohorts. The cohort included twelve gynecological patients with intact cervical lesions treated with external beam and brachytherapy. Pre-treatment CT images were registered to the simulation CT with respect to the target. Treatment catheter positions transformed into the planning CT coordinate system to evaluate localized catheter displacement and dose distributions calculated at each fraction. Dose was evaluated on the planning CT with planning contours and dwell locations at treatment position. Absolute deviation, depth and deflection angle for all patients were 4.6 ± 4.2 mm, -1.4 ± 4.0 mm, and 3.1 ± 2.3° respectively (n = 516 catheter positions for all treatment fractions and patients, mean ± SD). Absolute catheter deviation and deflection magnitude for interstitial treatments increased overall with each subsequent fraction with an overall increase of catheter retraction at each fraction (p0.005, n = 492 catheters, Kruskal-Wallis). A target EQD2 D90 reduction of 10 ± 10% and 7.7 ± 8.7% of the planned dose for interstitial and TR cohorts respectively. There was an overall increase in bladder and rectal doses at each fraction. Catheter tracking in interstitial and intracavitary gynecological treatments with CT imaging revealed significant changes in catheter positioning with respect to the target volume. Overall deviations increased in magnitude with each subsequent fraction in the interstitial treatments. This caused patient dosimetry deviations, including target dose reduction and adjacent OAR doses changes.

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.

Cervical cancer (CC) is the fourth leading cancer in women in the age group of 15-44 years globally. Experimental as well as epidemiological studies identified that type16 and 18 HPV cause 70% of precancerous cervical lesions as well as cervical cancer worldwide by bringing about genetic as well as epigenetic changes in the host genome. The insertion of the HPV genome triggers various defense mechanisms including the silencing of tumor suppressor genes as well as activation of oncogenes associated with cancer metastatic pathway. E6 and E7 are small oncoproteins consisting of 150 and 100 amino acids, respectively. These oncoproteins affect the regulation of the host cell cycle by interfering with p53 and pRb. Further, these oncoproteins adversely affect the normal functions of the host cell by binding to their signaling proteins. Recent studies demonstrated that E6 and E7 oncoproteins are potential targets for CC. Therefore, this review discusses the role of E6 and E7 oncoproteins in metastasis and drug resistance as well as their regulation, early oncogene mediated signaling pathways. This review also uncovers recent updates on molecular mechanisms of E6 and E7 mediated phytotherapy, gene therapy, immune therapy, and vaccine strategies as well as diagnosis through precision testing. Therefore, understanding the potential role of E6/E7 in metastasis and drug resistance along with targeted treatment, vaccine, and precision diagnostic strategies, could be useful for the prevention and treatment of cervical cancer.

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.

The prevalence of human papillomavirus (HPV) infection and HPV genotypes varies in different regions. However, there is little data on HPV prevalence and genotyping in Guangxi Province, South China. This study conducted a 10-year survey in a health center, to estimate the prevalence characteristics of HPV genotypes.By using polymerase chain reaction (PCR) amplification and nucleic acid molecular hybridization, the HPV genotypes were detected from 77,756 females who were patients of the Department of Obstetrics and Gynecology and those who visited the Health Management Center for a physical examination between August 2011 and November 2020. The prevalence, genotypes, age-related HPV infections, as well as chronological change of HPV prevalence, and the HPV genotype distribution were analyzed.The overall prevalence of HPV infection was 21.14% (16,439/77,756). The HPV infection rate differed significantly between the patients of the Department of Obstetrics and Gynecology and the women who underwent a physical examination (22.98% vs. 9.88%, p 0.05). The prevalence rates of high-risk HPV, low-risk HPV, mixed HPV (mixed high-risk, and low-risk HPV infection), and multiple HPV infections were 18.96% (14,739/77,756), 4.09% (3178/77,756), 1.90% (1478/77,756), and 4.94% (3838/77,756), respectively. The most prevalent genotypes were HPV 52, 16, and 58. The age-associated HPV prevalence showed bimodal curves, with the first peak at25 years and the second peak at56 years.This study provides baseline data on the HPV prevalence in the general female population of Nanning, Guangxi Province. Women25 and56 years old faced the greatest threat of HPV infection, and HPV 52, 16, and 58 were the most common genotypes.

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.