HPV-related metastatic retroperitoneal pelvic squamous cell carcinoma of unknown primary origin in a patient previously treated for endometrial cancer.

INTRODUCTION: Cancer of unknown primary (CUP) is metastatic disease with no identifiable site of origin. Retroperitoneal squamous cell carcinoma of unknown primary is extremely rare. There are limited reports regarding treatment recommendations and outcomes for women with this disease. PRESENTATION OF CASE: Here we present the case of a woman with human papillomavirus (HPV)-related metastatic retroperitoneal pelvic squamous cell carcinoma of unknown primary previously treated for endometrial cancer as well as a review of the existing reports on this topic. Surgical removal of the tumor was performed, the treatment had effective immediate results. DISCUSSION: There are a few reports describing CUPs in the retroperitoneal space. Most retroperitoneal tumors are asymptomatic and may be found incidentally during a regular examination, as in the case presented here. A full pelvic exam including inspection of the vulva, colposcopy and anoscopy should be performed, particularly in HPV-associated CUPs. Pathologic testing including immunohistochemistry and special staining and molecular testing of the tumor may be needed. CONCLUSION: It is important to find the primary origin of cancer to treat it successfully. If the primary tumor cannot be identified, immunohistochemistry and molecular testing of the tumor may help identify the nature of malignant disease and help guide appropriate treatment.

Metronidazole and cefazolin vs cefazolin alone for surgical site infection prophylaxis in gynecologic surgery at a comprehensive cancer center.

BACKGROUND: Surgical site infection is one of the most common complications of gynecologic cancer surgery. Current guidelines recommend the administration of cefazolin preoperatively to reduce surgical site infection rates for patients undergoing clean-contaminated surgeries such as hysterectomy. OBJECTIVE: To evaluate the impact of a quality improvement project adding metronidazole to cefazolin for antibiotic prophylaxis on surgical site infection rate for women undergoing gynecologic surgery at a comprehensive cancer center. STUDY DESIGN: This retrospective, single-center cohort study included patients who underwent surgery in the gynecologic oncology department from May 2017 to June 2023. Patients with penicillin allergies and those undergoing concomitant bowel resections and/or joint cases were excluded. The preintervention group patients had surgery from May 2017 to April 2022, and the postintervention group patients had surgery from April 2022 to June 2023. The primary outcome was a 30-day surgical site infection rate. Sensitivity analyses were performed to compare surgical site infection rates on the basis of actual antibiotics received and for those who had a hysterectomy. Factors independently associated with surgical site infection were identified using a multivariable logistic regression model adjusting for confounding variables. RESULTS: Of 3343 patients, 2572 (76.9%) and 771 (23.1%) were in the pre-post intervention groups, respectively. Most patients (74.7%) had a hysterectomy performed. Thirty-four percent of cases were for nononcologic (benign) indications. Preintervention patients were more likely to receive appropriate preoperative antibiotics (95.6% vs 90.7%; P<.001). The overall surgical site infection rate before the intervention was 4.7% compared with 2.6% after (P=.010). The surgical site infection rate for all patients who underwent hysterectomy was 4.9% (preintervention) vs 2.8% (postintervention) (P=.036); a similar trend was seen for benign cases (4.4% vs 2.4%; P=.159). On multivariable analysis, the odds ratio for surgical site infection was 0.49 (95% confidence interval, 0.38-0.63) for the postintervention compared with the preintervention group (P<.001). In a sensitivity analysis (n=3087), the surgical site infection rate was 4.5% for those who received cefazolin alone compared with 2.3% for those who received cefazolin plus metronidazole, with significantly decreased odds of surgical site infection for the cefazolin plus metronidazole group (adjusted odds ratio, 0.40 [95% confidence interval, 0.30-0.53]; P<.001). Among only those who had a hysterectomy performed, the odds of surgical site infection were significantly reduced for those in the postintervention group (adjusted odds ratio, 0.63 [95% confidence interval, 0.47-0.86]; P=.003). CONCLUSION: The addition of metronidazole to cefazolin before gynecologic surgery decreased the surgical site infection rate by half, even after accounting for other known predictors of surgical site infection and differences in practice patterns over time. Providers should consider this combination regimen in women undergoing gynecologic surgery, especially for cases involving hysterectomy.

National Breast, Cervical, and Colorectal Cancer Screening Use in Federally Qualified Health Centers.

Importance: Federally qualified health centers (FQHCs) deliver health care to nearly 30 million underserved persons across the US, yet nationwide and state-level breast, cervical, and colorectal cancer screening use in FQHCs is not described. Furthermore, it is unknown how the underscreened FQHC population contributes to the total underscreened population at national and state levels. Objective: To describe national- and state-level breast, cervical, and colorectal cancer screening use among individuals served by FQHCs in the US and to estimate the percentage of underscreened individuals in the general population served by FQHCs. Design, Setting, and Participants: This cross-sectional analysis of cancer screening used data from January 1 through December 31, 2020, from the FQHC Uniform Data System, reported by 1364 FQHCs across the US, and self-reported estimates from the Behavioral Risk Factor Surveillance System. Participants were 16 696 692 US adults served by FQHCs who were eligible for breast (age, 50-74 years), cervical (age, 21-64 years), and colorectal (age, 50-75 years) cancer screening. Analyses were conducted between January 1 and June 30, 2023. Exposures: Breast, cervical, and colorectal cancer screening. Main Outcomes and Measures: Percentages of breast, cervical, and colorectal cancer screening-eligible individuals up to date on screening. Results: A total of 3 162 882 breast, 7 444 465 cervical, and 6 089 345 colorectal screening-eligible individuals were served by FQHCs in 2020. Nationally, screening use in FQHCs was 45.4% (95% CI, 45.4%-45.5%) for breast cancer, 51.0% (95% CI, 51.0%-51.1%) for cervical cancer, and 40.2% (95% CI, 40.1%-40.2%) for colorectal cancer. Screening use among the US general population was 78.2% (95% CI, 77.6%-78.9%) for breast cancer, 82.9% (95% CI, 82.3%-83.4%) for cervical cancer, and 72.3% (95% CI, 71.7%-72.8%) for colorectal cancer. The contribution of the underscreened population served by FQHCs to the national underscreened general population was 16.9% (95% uncertainty interval [UI], 16.4%-17.4%) for breast cancer, 29.7% (95% UI, 28.8%-30.7%) for cervical cancer, and 14.7% (95% UI, 14.4%-15.0%) for colorectal cancer. Conclusions and Relevance: Findings from this national cross-sectional study indicated major gaps in cancer screening use in FQHCs in the US. Improved prevention is urgently needed to address screening disparities.

Multiscale Optical Imaging Fusion for Cervical Precancer Diagnosis: Integrating Widefield Colposcopy and High-Resolution Endomicroscopy.

OBJECTIVE: Early detection and treatment of cervical precancers can prevent disease progression. However, in low-resource communities with a high incidence of cervical cancer, high equipment costs and a shortage of specialists hinder preventative strategies. This manuscript presents a low-cost multiscale in vivo optical imaging system coupled with a computer-aided diagnostic system that could enable accurate, real-time diagnosis of high-grade cervical precancers. METHODS: The system combines portable colposcopy and high-resolution endomicroscopy (HRME) to acquire spatially registered widefield and microscopy videos. A multiscale imaging fusion network (MSFN) was developed to identify cervical intraepithelial neoplasia grade 2 or more severe (CIN 2+). The MSFN automatically identifies and segments the ectocervix and lesions from colposcopy images, extracts nuclear morphology features from HRME videos, and integrates the colposcopy and HRME information. RESULTS: With a threshold value set to achieve sensitivity equal to clinical impression (0.98 [p = 1.0]), the MSFN achieved a significantly higher specificity than clinical impression (0.75 vs. 0.43, p = 0.000006). CONCLUSION: Our findings show that multiscale optical imaging of the cervix allows the highly sensitive and specific detection of high-grade precancers. SIGNIFICANCE: The multiscale imaging system and MSFN could facilitate the accurate, real-time diagnosis of cervical precancers in low-resource settings.

Phase 1b study of intraperitoneal ipilimumab and nivolumab in patients with recurrent gynecologic malignancies with peritoneal carcinomatosis.

BACKGROUND: Intravenous immune checkpoint blockade (ICB) has shown poor response rates in recurrent gynecologic malignancies. Intraperitoneal (i.p.) ICB may result in enhanced T cell activation and anti-tumor immunity. METHODS: In this phase 1b study, registered at Clinical. TRIALS: gov (NCT03508570), initial cohorts received i.p. nivolumab monotherapy, and subsequent cohorts received combination i.p. nivolumab every 2 weeks and i.p. ipilimumab every 6 weeks, guided by a Bayesian design. The primary objective was determination of the recommended phase 2 dose (RP2D) of the combination. Secondary outcomes included toxicity, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). FINDINGS: The trial enrolled 23 patients: 18 with ovarian cancer, 2 with uterine cancer, and 3 with cervical cancer. Study evaluable patients (n = 16) received a median of 2 prior lines of therapy (range: 1-8). Partial response was observed in 2 patients (12.5%; 1 ovarian, 1 uterine), and complete response was observed in 1 patient (6.3%) with cervical cancer, for an ORR of 18.8% (95% confidence interval: 4.0%-45.6%). The median duration of response was 14.8 months (range: 4.1-20.8), with one complete response ongoing. Median PFS and OS were 2.7 months and not reached, respectively. Grade 3 or higher immune-related adverse events occurred in 2 (8.7%) patients. CONCLUSIONS: i.p. administration of dual ICB is safe and demonstrated durable responses in a subset of patients with advanced gynecologic malignancy. The RP2D is 3 mg/kg i.p. nivolumab every 2 weeks plus 1 mg/kg ipilimumab every 6 weeks. FUNDING: This work was funded by Bristol Myers Squibb (CA209-9C7), an MD Anderson Cancer Center Support Grant (CA016672), the Ovarian Cancer Moon Shots Program, the Emerson Collective Fund, and a T32 training grant (CA101642).

Interventions to increase follow-up of abnormal cervical cancer screening results: A systematic literature review and meta-analysis.

INTRODUCTION: Ensuring timely follow-up of abnormal screening results is essential for eliminating cervical cancer. OBJECTIVE: The purpose of the study was to review single and multicomponent interventions designed to improve follow-up of women with abnormal cervical cancer screening results. We report on effectiveness across studies, and describe what aspects of these interventions might be more impactful. METHODS: Publications were searched between January 2000 and December 2022. The search included observational, quasi-experimental (pre-post studies) and randomized controlled studies describing at least one intervention to increase follow-up of women with abnormal cervical cancer screening results. Outcomes of studies included completion of any follow-up (i.e., attending a follow-up appointment), timely diagnosis (i.e., colposcopy results within 90 days of screening) and time to diagnostic resolution (i.e., days between screening and final diagnosis). We assessed risk of bias for observational and quasi-experimental studies using the Newcastle-Ottawa Scale (NOS) tool and the Cochrane collaboration tool for randomized studies. We conducted a meta-analysis using studies where data were provided to estimate a summary average effect of the interventions on follow-up of patients and to identify characteristics of studies associated with an increased effectiveness of interventions. We extracted the comparison and intervention proportions of women with follow-up before and after the intervention (control and intervention) and plotted the odds ratios (ORs) of completing follow-up along with the 95% confidence intervals (CIs) using forest plots for the interventions vs. controls when data were available. FINDINGS: From 7,457 identified studies, 28 met the inclusion criteria. Eleven (39%) of the included studies had used a randomized design. Most studies (63%) assessed completion of any follow-up visit as the primary outcome, whereas others measured time to definite diagnosis (15%) or diagnostic resolution (22%). Navigation was used as a type of intervention in 63% of the included studies. Most interventions utilized behavioral approaches to improve outcomes. The overall estimate of the OR for completion of follow-up for all interventions was 1.81 (1.36-2.42). The highest impact was for programs using more than one approach (multicomponent interventions) to improve outcomes with OR = 3.01 (2.03-4.46), compared with studies with single intervention approaches with OR = 1.56 (1.14-2.14). No statistical risks were noted from publication bias or small-study effects in the studies reviewed. CONCLUSION: Our findings revealed large heterogeneity in how follow-up of abnormal cervical cancer screening results was defined. Our results suggest that multicomponent interventions were more effective than single component interventions and should be used to improve follow-up after abnormal cervical cancer screening results. Navigation appears to be an important tool for improving follow-up. We also provide recommendations for future studies and implications for policy in terms of better defining outcomes for these interventions.

The global burden of cervical cancer requiring surgery: database estimates.

BACKGROUND: Scaling up surgical services for cervical cancer in low and middle income countries requires quantification of the need for those services. The aim of this study was to estimate the global burden of cervical cancer for which access to surgery is required. METHODS: This was a retrospective analysis of publicly available data. Cervical cancer incidence was extracted for each country from the World Health Organization, International Agency for Research, Global Cancer Observatory. The proportion of cases requiring surgery was extrapolated from the United States Surveillance, Epidemiology and End-Result database. The need for cervical cancer surgery was tested against development indicators. RESULTS: Data were available for 175 countries, representing 2.9 billion females aged 15 and over. There were approximately 566,911 women diagnosed with cervical cancer (95% CI 565,462-568,360). An estimated 56.9% of these women (322,686) would require surgery for diagnosis, treatment or palliation (95% CI 321,955 - 323,417). Cervical cancers for which surgery is required represent less than 1% of cancers in high income countries, and nearly 10% of cancers in low income countries. CONCLUSIONS: At least 300,000 cervical cancer cases worldwide require access to surgical services annually. Gathering data on available cervical cancer surgery services in LMIC are a critical next step.

Efficacy, safety, and feasibility of Apixaban for postoperative venous thromboembolism prophylaxis following open gynecologic cancer surgery at a comprehensive cancer center.

OBJECTIVES: To evaluate safety, efficacy, and feasibility of apixaban for postoperative venous thromboembolism (VTE) prophylaxis following open gynecologic cancer surgery at a comprehensive cancer center. METHODS: This retrospective, cohort study included patients with gynecologic cancer who underwent open surgery between 3/2021 and 3/2023 and received 28-day postoperative VTE prophylaxis. Patients on therapeutic anticoagulation preoperatively were excluded. Predictors of 90- and 30-day VTE and 30-day bleeding events were determined using multivariable logistic regression, adjusting for known confounders. RESULTS: 452 patients were included in the cohort: 348 received apixaban and 104 received enoxaparin. Those who received enoxaparin were more likely to be American Society of Anesthesiologists class III/IV (compared to I/II) (p = 0.033), current or former smokers (p = 0.012) and have a higher BMI (p < 0.001), Charlson Comorbidity Index (p = 0.005), and age (p = 0.046). 30-day VTE rate was significantly lower in the apixaban group (0.6%) compared to the enoxaparin group (6.2%) (adjusted OR 0.13, 95% CI 0.03-0.56; p = 0.006). 90-day VTE rate was 2.7% and 6.2% in the apixaban and enoxaparin groups, respectively (adjusted OR 0.85, 95% CI 0.38-1.92; p = 0.704). Major bleeding complications (2.4% vs. 2.0%) and minor bleeding complications (0.9% vs. 3.0%) were similar in the apixaban and enoxaparin groups, respectively, on multivariate analyses. The median patient out of pocket cost was $10 (IQR 0.0-40.0) for apixaban and $20 (IQR 3.7-67.7) for enoxaparin (p = 0.001). CONCLUSIONS: Our findings along with previously published data suggest that apixaban should be considered the standard of care for VTE prophylaxis in patients undergoing open surgery for gynecologic malignancies.

Self-Sampling for Human Papillomavirus Testing: Acceptability in a U.S. Safety Net Health System.

INTRODUCTION: Self-sampling for human papillomavirus testing is increasingly recognized as a strategy to expand cervical cancer screening access and utilization. Acceptability is a key determinant of uptake. This study assesses the acceptability of and experiences with mailed self-sampling kits for human papillomavirus testing among underscreened patients in a safety net health system. METHODS: A nested telephone survey was administered between 2021 and 2023 to a sample (n=272) of the 2,268 participants enrolled in the Prospective Evaluation of Self-Testing to Increase Screening trial. Trial participants include patients of a safety net health system aged 30-65 years who were not up to date on screening. Participants were asked about barriers to provider-performed screening. Kit users and nonusers were asked about their experiences. RESULTS: Prevalent barriers to provider-performed screening included perceived discomfort of pelvic examination (69.4%), being uncomfortable with male providers (65.4%), and embarrassment (57.0%). Among participants who reported using the mailed kit (n=164), most reported good experiences (84.8%). Most reported self-sampling as more/equally convenient (89.0%), less/equally embarrassing (99.4%), and less/equally stressful (95.7%) than provider-performed screening. Among kit nonusers (n=43), reasons for not using the kit included forgetting about it (76.7%), preferring provider-performed screening (76.7%), and fearing cancer (67.4%). CONCLUSIONS: Prospective Evaluation of Self-Testing to Increase Screening trial participants generally had a positive experience with self-sampling for human papillomavirus testing. Increased comfort and reduced embarrassment/anxiety with self-sampling are relevant attributes because these were the most prevalent reported barriers to provider-performed screening. High acceptability suggests potentially high uptake when self-sampling for human papillomavirus testing receives regulatory approval and is available in safety net health systems.

Exploratory analysis of the cervix tumoral HPV antigen-specific T-cell repertoire during chemoradiation and after brachytherapy.

BACKGROUND: Chemoradiation (CRT) may modulate the immune milieu as an in-situ vaccine. Rapid dose delivery of brachytherapy has unclear impact on T-cell repertoires. HPV-associated cancers express viral oncoproteins E6/E7, which enable tracking antigen/tumor-specific immunity during CRT. METHODS: Thirteen cervical cancer patients on a multi-institutional prospective protocol from 1/2020-1/2023 underwent standard-of-care CRT with pulsed-dose-rate brachytherapy boost (2 fractions). Cervix swabs at various timepoints underwent multiplex DNA deep sequencing of the TCR-ß/CDR3 region with immunoSEQ. Separately, HPV-responsive T-cell clones were also expanded ex vivo. Statistical analysis was via Mann-Whitney-U. RESULTS: TCR productive clonality, templates, frequency, or rearrangements increased post-brachytherapy in 8 patients. Seven patients had E6/E7-responsive evolution over CRT with increased productive templates (ranges: 1.2-50.2 fold-increase from baseline), frequency (1.2-1.7), rearrangements (1.2-40.2), and clonality (1.2-15.4). Five patients had HPV-responsive clonal expansion post-brachytherapy, without changes in HPV non-responsive clones. Epitope mapping revealed VDJ rearrangements targeting cervical cancer-associated antigens in 5 patients. The only two patients with disease recurrence lacked response in all metrics. A lack of global TCR remodeling correlated with worse recurrence-free survival, p = 0.04. CONCLUSION: CRT and brachytherapy alters the cervical cancer microenvironment to facilitate the expansion of specific T-cell populations, which may contribute to treatment efficacy.

Malignant neoplasms of the vagina: A 30-year review from the Republic of Belarus.

Objective: To perform a retrospective review of patients diagnosed with vaginal malignant neoplasms (VMN) in the Republic of Belarus. Methods: The Belarusian Cancer Registry was reviewed for patients diagnosed with VMN from 1990 to 2019. The data collected included age at diagnosis, demographic information, histology, stage, treatment modalities, and outcomes. Data were compared across decades (1990-1999, 2000-2009, and 2010-2019). Results: A total of 868 patients were diagnosed with VMN in Belarus between 1990 and 2019. The estimated age-standardized incidence rate of VMN per 100,000 female population increased from 0.1 in 1999 to 0.4 in 2019 (p < 0.05). The mortality rate for this period was 0.0-0.2 per 100,000 female population. Of all newly diagnosed cases of VMN, 70.9% (n = 615) lived in urban centers and 29.1% (n = 253) lived in rural areas. The most common histological type was squamous cell carcinoma, accounting for 78.4% of cases. The median age at diagnosis was 63.4 years (range, 15.0-87.0 years). When compared across the three decades, the number of stage I cases increased slightly more than twofold (from 19.1% to 38.5% for 1990-1999 to 2010-2019). Furthermore, the number of stage III cases decreased from 30.3% to 13.0% from 1990 to 1999 to 2010-2019. There were no significant changes in the number of patients diagnosed with stage II or IV disease over time. The overall 5-year survival rate for the entire group was 68.7 ± 5.1%, with no statistically significant difference between women living in urban centers vs. rural areas (67.8 ± 5.1% vs. 65.8 ± 10.4%; p = 0.99). However, there was a 26.2% increase in the 5-year survival rate for the entire group over the study period. This increase was higher for women living in rural areas (+61.7%) than for those in urban centers (+51.3%); p > 0.05. Furthermore, a comparison of 5-year adjusted survival rates between 2000 and 2015 showed increased survival for stages I, II, and III, with the most significant increase noted for stage III disease (2.4-fold increase). Conclusions: This retrospective study found that the survival rates of women with VMN in Belarus have improved over the past 30 years. This is likely due to improvements in early detection as well as improved approaches to treatment, particularly for those living in rural areas. Additional study is needed to further understand and improve the outcomes of women diagnosed with VMN in Belarus.

Addressing cervical cancer disparities in Texas: Expansion of a community-based prevention initiative for medically underserved populations.

Although cervical cancer is preventable, significant disparities exist in access to screening and prevention services. In medically underserved areas (MUAs) of Texas, these rates are 55% higher compared to the remainder of the US. In 2019, we expanded a multicomponent, comprehensive program to improve cervical cancer prevention in partnership with 13 clinics and mobile vans in MUAs of Texas. Our multicomponent intervention program consists of community education and patient navigation coupled with a training/mentoring program for local medical providers to perform diagnostic procedures and treatment for patients with abnormal screening results. Hands-on training courses to learn these skills are coupled with biweekly telementoring conferences using Project ECHO® (Extension for Community Healthcare Outcomes). This program was implemented in 2015 and expanded to other MUAs in Texas in 2019. From March 2019 to August 2022, 75,842 individuals were educated about cervical cancer screening and HPV vaccination. A total of 44,781 women underwent screening for cervical cancer, and 2,216 underwent colposcopy and 264 underwent LEEP. High-grade cervical dysplasia was diagnosed in 658 individuals and invasive cervical cancer in 33 individuals. We trained 22 providers to perform colposcopy and/or LEEP. In addition, 78 Project ECHO telementoring sessions were held with an average of 42 attendees per session, with 72 individual patient cases discussed. Our comprehensive community-based prevention initiative for medically underserved populations has led to a significant number of individuals undergoing cervical cancer screening in MUAs, as well as improved access to colposcopy and LEEP services.

Retroperitoneal Hematoma as an Atypical Presentation of Choriocarcinoma: A Case Report.

A 38-year-old female with an etonogestrel implant in place and history of previous ectopic pregnancy presented with acute abdominal pain and vaginal bleeding. She was found to have a beta-hCG of >12,000 mIU/mL and free fluid noted on a focused assessment with sonography in trauma exam. She underwent an emergent diagnostic laparoscopy due to the suspicion of a ruptured ectopic pregnancy. Findings at the time of surgery included a normal-appearing uterus and left fallopian tube, a surgically absent right fallopian tube and large volume hemoperitoneum with a rapidly expanding left retroperitoneal hematoma. A postoperative computerized tomography (CT) angiogram suggested active bleeding from a pseudoaneurysm of the left renal artery which was successfully embolized by interventional radiology. Biopsy confirmed gestational trophoblastic neoplasia (GTN) after metastases to the brain. In this report, we describe the details of this case of GTN with an atypical presentation.

Müllerian-Type Clear Cell Carcinoma of Donor Origin in a Male Patient with a Kidney Transplant: Ascertained by Molecular Testing.

Clear cell carcinomas of Müllerian origin have a strong female predominance and only extremely rarely will arise within the kidney, presumably due to ectopic Müllerian embryogenesis. Herein, we report a unique case of metastatic Müllerian type clear cell carcinoma in a 37-year-old patient who had previously received a transplanted kidney from his father at age 11 (due to severe bilateral vesicoureteral reflux) and remained on chronic immunosuppression. The tumor was highly aggressive and demonstrated somatic mutations in NF2 and SETD2. Imaging of the transplanted kidney did not reveal any clear evidence of malignancy. However, targeted multigene sequencing and short tandem repeat testing revealed that the cancer was of donor origin, presumably from ectopic Müllerian tissue transplanted to the patient along with the kidney graft. The tumor was resistant to first-line therapy with a triple combination of carboplatin plus paclitaxel plus bevacizumab, as well as to second-line immunotherapy with nivolumab plus ipilimumab after tapering down the patient's immunosuppression. Despite the tumor being genetically distinct from the host, the use of immune checkpoint therapy with nivolumab plus ipilimumab did not yield a response. This unique case showcases the value of molecular testing in determining the tumor origin in patients with solid organ transplants who present with cancers of unknown primary. This can prompt the potential investigation of other recipients from the same donor.

The Mulher Study: cervical cancer screening with primary HPV testing in Mozambique.

OBJECTIVE: To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally. METHODS: Women aged 30-49 years were prospectively enrolled and offered primary HPV testing using either self-collected or provider-collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation. If ineligible, they were referred for excision with a loop electrosurgical excision procedure, for cold knife conization, or for cervical biopsy if malignancy was suspected. RESULTS: Between January 2020 and January 2023, 9014 patients underwent cervical cancer screening. Median age was 37 years (range 30-49) and 4122 women (45.7%) were patients living with HIV. Most (n=8792, 97.5%) chose self-collection. The HPV positivity rate was 31.1% overall and 39.5% among patients living with HIV. Of the 2805 HPV-positive patients, 2588 (92.3%) returned for all steps of their diagnostic work-up and treatment, including ablation (n=2383, 92.1%), loop electrosurgical excision procedure (n=169, 6.5%), and cold knife conization (n=5, 0.2%). Thirty-one patients (1.2%) were diagnosed with cancer and referred to gynecologic oncology. CONCLUSION: It is feasible to perform cervical cancer screening with primary HPV testing and follow-up in low-resource settings. Participants preferred self-collection, and the majority of screen-positive patients completed all steps of their diagnostic work-up and treatment. Our findings provide important information for further implementation and scale-up of cervical cancer screening and treatment services as part of the WHO global strategy for the elimination of cervical cancer.

Scanning darkfield high-resolution microendoscope for label-free microvascular imaging.

Characterization of microvascular changes during neoplastic progression has the potential to assist in discriminating precancer and early cancer from benign lesions. Here, we introduce a novel high-resolution microendoscope that leverages scanning darkfield reflectance imaging to characterize angiogenesis without exogenous contrast agents. Scanning darkfield imaging is achieved by coupling programmable illumination with a complementary metal-oxide semiconductor (CMOS) camera rolling shutter, eliminating the need for complex optomechanical components and making the system portable, low-cost (<$5,500) and simple to use. Imaging depth is extended by placing a gradient-index (GRIN) lens at the distal end of the imaging fiber to resolve subepithelial microvasculature. We validated the capability of the scanning darkfield microendoscope to visualize microvasculature at different anatomic sites in vivo by imaging the oral cavity of healthy volunteers. Images of cervical specimens resected for suspected neoplasia reveal distinct microvascular patterns in columnar and squamous epithelium with different grades of precancer, indicating the potential of scanning darkfield microendoscopy to aid in efforts to prevent cervical cancer through early diagnosis.

Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring.

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other body sites are also significantly associated with survival in colorectal, lung, head and neck, and skin cancers. Our findings demonstrate that lactic acid bacteria in the tumor microenvironment can alter tumor metabolism and lactate signaling pathways, causing therapeutic resistance. Lactic acid bacteria could be promising therapeutic targets across cancer types.

Elimination of cervical cancer in Latin America (Project ECHO-ELA): lessons from phase one of implementation.

We describe the outcomes of The Extension for Community Healthcare Outcomes-Elimination of Cervical Cancer in The Americas (ECHO-ELA) program, which was developed as a tri-lateral cooperation between Pan American Health Organization (PAHO), the U.S. National Cancer Institute (NCI) and The University of Texas MD Anderson Cancer Center (MD Anderson). The program's purpose is to disseminate strategies for cervical cancer prevention and is structured around the three pillars of the World Health Organization's (WHO) Cervical Cancer Elimination Strategy and the associated 90-70-90 target goals. The target audience includes health authorities from Latin American and Caribbean countries, as well as PAHO's non-communicable disease Focal Points in country offices as well as clinical and public health collaborators. The virtual sessions are held in Spanish for 1.5 hours every month using the ECHO® format. From May 2020 to June 2021, 14 ECHO sessions were held with an average of 74 participants per session (range: 46 - 142). We conducted two anonymous surveys (baseline and follow up) and two focus groups. Respondents stated that the topics they learned the most about included the state of HPV vaccination in the region and strategies for implementing HPV vaccination. Identified needs included support between ECHO sessions and country-specific technical assistance. The ECHO-ELA program provides a forum for increased collaboration between countries in Latin America/Caribbean and the dissemination of best-practice strategies to reach the WHO Cervical Cancer Elimination target goals.

Se describen los resultados del programa ECHO® (Extension for Community Healthcare Outcomes) para la eliminación del cáncer cervicouterino en las Américas (ECHO-ELA), que se concibió como una cooperación trilateral entre la Organización Panamericana de la Salud (OPS), el Instituto Nacional del Cáncer de los Estados Unidos (NCI) y el centro contra el cáncer MD Anderson (MD Anderson) de la Universidad de Texas. La finalidad del programa es difundir las estrategias para la prevención del cáncer cervicouterino, y está estructurado en torno a los tres pilares de la estrategia para la eliminación del cáncer cervicouterino de la Organización Mundial de la Salud (OMS) y los objetivos 90-70-90 conexos. El público destinatario comprende autoridades de salud de países de América Latina y el Caribe, así como los puntos focales de la OPS para las enfermedades no transmisibles en las Representaciones en los países, además de colaboradores en el ámbito clínico y de la salud pública. Las sesiones virtuales se llevan a cabo en español, durante 1,5 horas cada mes, utilizando el formato ECHO®. De mayo del 2020 a junio del 2021 se celebraron 14 sesiones de ECHO, con un promedio de 74 participantes por sesión (límites: 46-142). Se realizaron dos encuestas anónimas (al inicio y de seguimiento) y dos grupos de opinión. Los encuestados declararon que los temas sobre los que más aprendieron fueron la situación de la vacunación contra el VPH en la región y las estrategias para poner en marcha la vacunación contra el VPH. Entre las necesidades mencionadas figuraban el apoyo entre las sesiones de ECHO y la asistencia técnica específica para cada país. El programa ECHO-ELA brinda un foro para una mayor colaboración entre los países de América Latina y el Caribe y para difundir las estrategias sobre las mejores prácticas, a fin de alcanzar los objetivos de la OMS de eliminación del cáncer cervicouterino.

Este trabalho descreve os resultados do programa Extension for Community Healthcare Outcomes para eliminação do câncer do colo do útero nas Américas (ECHO ELA), desenvolvido na forma de cooperação trilateral entre a Organização Pan-Americana da Saúde (OPAS), o Instituto Nacional do Câncer dos Estados Unidos (NCI) e o MD Anderson Cancer Center da Universidade do Texas (MD Anderson). O programa visa a disseminar estratégias para a prevenção do câncer do colo do útero e está estruturado em torno dos três pilares da estratégia de eliminação do câncer do colo do útero da Organização Mundial da Saúde (OMS) e das Metas 90-70-90 associadas. O público-alvo inclui autoridades sanitárias de países da América Latina e do Caribe, bem como os pontos focais de doenças não transmissíveis nas representações da OPAS nos países, além de colaboradores clínicos e de saúde pública. Todos os meses, são realizadas sessões virtuais de uma hora e meia em espanhol usando o formato ECHO®. No período de maio de 2020 a junho de 2021, foram realizadas 14 sessões do ECHO, com uma média de 74 participantes por sessão (variação: 46 a 142). Foram realizadas duas enquetes anônimas (linha de base e acompanhamento) e dois grupos focais. Os entrevistados afirmaram que os tópicos sobre os quais mais aprenderam foram a situação da vacinação contra o HPV na região e as estratégias para implementar a vacinação contra o HPV. As necessidades identificadas incluíam apoio entre as sessões do ECHO e assistência técnica específica para o país. O programa ECHO ELA oferece um fórum para aumentar a colaboração entre os países da América Latina e do Caribe e difundir melhores práticas para atingir as metas de eliminação do câncer do colo do útero da OMS.