Efficacy of Cobas HPV testing for predicting grade 2+ cervical intraepithelial neoplasia in a cancer prevention center and a gynecologic oncology clinic: A single-institution experience.

BACKGROUND: To evaluate the efficacy of Cobas human papillomavirus (HPV) testing to predict cervical intraepithelial neoplasia of grade 2 or higher (CIN2+), Cobas HPV testing results were correlated with follow-up biopsy in patients from Cancer Prevention Center (CPC) and Gynecologic Oncology Clinic (GOC) of The University of Texas MD Anderson Cancer Center. METHODS: Institutional data for patients who underwent Cobas HPV and Papanicolaou (Pap) cytology cotesting from 2019 to 2020 were retrospectively reviewed. Surgical follow-up results were compared with Cobas HPV testing results in two populations. RESULTS: A total of 2226 patients, including 921 women (mean age, 55.2 years) seen at the CPC and 1305 women (mean age, 49.3 years) seen at the GOC, were included. Specimens from GOC patients had a significantly higher HPV positivity rate than did those from CPC patients (22.9% vs. 10.1%; p < .001). Cobas HPV testing was positive in all seven CPC patients with surgical follow-up results showing CIN2+. Among 36 GOC patients with CIN2+ lesions, five patients had HPV-/Pap+ testing results. Although only seven CPC patients had CIN2+, Cobas HPV testing showed 100% sensitivity for predicting CIN2+ in this group. Sensitivity for CIN2+ was 86.5% in the GOC group, whereas 13.9% of GOC patients with CIN2+ had negative HPV testing results. CONCLUSIONS: Cobas HPV testing was highly efficacious for predicting CIN2+ lesions in the low-risk CPC population, which supports HPV primary screening for cervical cancer in low-risk populations. For high-risk patients, especially those with a history of CIN2+/cervical cancer, HPV/Pap cotesting may still be necessary to maintain a high clinical sensitivity for CIN2+.

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.

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.

HPV-related anal cancer is associated with changes in the anorectal microbiome during cancer development.

Background: Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease. Methods: Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade lower genital tract dysplasia. Anorectal tumor swabs were prospectively collected from patients with biopsy-confirmed locally advanced SCCA prior to receiving standard-of-care chemoradiotherapy (CRT). Patients with high-grade lower genital tract dysplasia without anal dysplasia were considered high-risk (HR Normal). 16S V4 rRNA Microbiome sequencing was performed for anal swabs. Alpha and Beta Diversity and composition were compared for HR Normal, anal dysplasia, and anal cancer. Results: 60 patients with high-grade lower genital tract dysplasia were initially enrolled. Seven patients had concurrent anal dysplasia and 44 patients were considered HR Normal. Anorectal swabs from 21 patients with localized SCCA were included, sequenced, and analyzed in the study. Analysis of weighted and unweighted UniFrac distances demonstrated significant differences in microbial community composition between anal cancer and HR normal (p=0.018). LEfSe identified that all three groups exhibited differential enrichment of specific taxa. Peptoniphilus (p=0.028), Fusobacteria (p=0.0295), Porphyromonas (p=0.034), and Prevotella (p=0.029) were enriched in anal cancer specimens when compared to HR normal. Conclusion: Although alpha diversity was similar between HR Normal, dysplasia and cancer patients, composition differed significantly between the three groups. Increased anorectal Peptoniphilus, Fusobacteria, Porphyromonas, and Prevotella abundance were associated with anal cancer. These organisms have been reported in various gastrointestinal cancers with roles in facilitating the proinflammatory microenvironment and neoplasia progression. Future work should investigate a potential role of microbiome analysis in screening for anal dysplasia and investigation into potential mechanisms of how these microbial imbalances influence the immune system and anal carcinogenesis.

Malignancy in pregnancy: Multimodality imaging and treatment.

The diagnosis of cancer is increasingly made in the pregnant population, thought to be from the increasing average age of pregnancy and the use of prenatal fetal noninvasive screening techniques, leading to incidental detection of cancer in the mother. Complex challenges are associated with imaging, diagnosis, staging, and treatment of cancers in this patient population, which require highly specialized interdisciplinary management. This report discusses the use of multimodality imaging and safety considerations in pregnant patients, reviews the current guidelines for ionizing radiation imaging techniques, and presents a series of commonly and uncommonly encountered cancers in pregnancy with current diagnostic imaging guidelines. The authors also discuss the role of multidisciplinary management and treatment options and provide an overview of therapy-related considerations in the age of novel anticancer therapies. PLAIN LANGUAGE SUMMARY: The diagnosis and management of pregnant patients who have cancer are actively evolving as novel imaging techniques and anticancer therapies are being developed. Radiologically, there are inherent difficulties in balancing the minimization of fetal ionization while acquiring diagnostic quality imaging necessary for the diagnosis, staging, and treatment of maternal disease. Standardized imaging protocols are still being developed, with evolving imaging guidelines coupled with rapidly expanding research and development of novel anticancer therapies, which come with their side effects and complications. Caring for this patient population is especially challenging and requires specialized multidisciplinary attention.

Condyloma and coincidental epidermodysplasia verruciformis acanthoma positive for human papillomavirus-14 and -21.

Epidermodysplasia verruciformis (EDV) is a rare genodermatosis that predisposes individuals to persistent infection with ß-human papillomavirus (HPV) genotypes. The term EDV acanthoma may be applied to lesions with incidental findings of EDV-defining histopathological features without clinical signs of EDV. We report a case of HPV-14- and -21-positive EDV acanthoma arising in association with condyloma in a female patient with a history of low-grade squamous intraepithelial lesion of the cervix positive for high-risk HPV (non-16/18), chronic kidney disease, and systemic lupus erythematosus. The patient had no family or personal history of EDV, but the patient was on immunosuppressive therapy with mycophenolate mofetil and prednisone. A biopsy specimen from one of the perianal lesions revealed histopathologic changes consistent with EDV in the setting of condyloma. Molecular testing showed HPV-14 and -21, which supported the coexistence of condyloma with EDV acanthoma.

A Cross-Sectional Study of the Prevalence of Anal Dysplasia among Women with High-Grade Cervical, Vaginal, and Vulvar Dysplasia or Cancer: The PANDA Study.

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection is a risk factor for anal cancer, yet no anal cancer screening guidelines exist for women with lower genital tract HPV-related disease. We sought to describe the prevalence of anal HR-HPV or cytologic abnormalities in such women. METHODS: This cross-sectional study was performed between October 2018 and December 2021. Inclusion criteria were ≥21 years of age and a prior diagnosis of high-grade dysplasia/cancer of the cervix, vagina, or vulva. Participants underwent anal cytology and anal/cervicovaginal HR-HPV testing. Women with abnormal anal cytology were referred for high-resolution anoscopy (HRA). RESULTS: 324 evaluable women were enrolled. Primary diagnosis was high-grade dysplasia/cancer of the cervix (77%), vagina (9%), and vulva (14%). Anal HR-HPV was detected in 92 patients (28%) and included HPV-16 in 24 (26%), HPV-18 in 6 (7%), and other HR-HPV types in 72 (78%) patients. Anal cytology was abnormal in 70 patients (23%) and included atypical squamous cells of undetermined significance (80%), low-grade squamous intraepithelial lesion (9%), high-grade intraepithelial lesion (HSIL; 1%), and atypical squamous cells-cannot rule out HSIL (10%). Of these patients, 55 (79%) underwent HRA. Anal biopsies were performed in 14 patients: 2 patients had anal intraepithelial neoplasia (AIN) 2/3, 1 patient had AIN 1, and 11 patients had negative biopsies. Both patients with AIN 2/3 had a history of cervical dysplasia. CONCLUSIONS: Our results suggest an elevated risk of anal HR-HPV infection and cytologic abnormalities in women with lower genital tract dysplasia/cancer. IMPACT: These results add to the growing body of evidence suggesting the need for evaluation of screening methods for anal dysplasia/cancer in this patient population to inform evidence-based screening recommendations.

Prospective phase II trial of levonorgestrel intrauterine device: nonsurgical approach for complex atypical hyperplasia and early-stage endometrial cancer.

BACKGROUND: The incidence of complex atypical hyperplasia and early-stage endometrioid endometrial cancer is increasing, in part owing to the epidemic of obesity, which is a risk factor tightly linked to the development of endometrial hyperplasia and cancer. The standard upfront treatment for complex atypical hyperplasia and early-stage endometrial cancer is hysterectomy. However, nonsurgical treatment of early-stage endometrial neoplasia may be necessary owing to medical comorbidities precluding surgery or desired future fertility. OBJECTIVE: This study aimed to evaluate the efficacy of the levonorgestrel intrauterine device to treat complex atypical hyperplasia and grade 1 endometrioid endometrial carcinoma. STUDY DESIGN: A single-institution, single-arm, phase II study of the levonorgestrel intrauterine device (52 mg levonorgestrel, Mirena) was conducted in patients with complex atypical hyperplasia or grade 1 endometrioid endometrial cancer. The primary endpoint was pathologic response rate at 12 months, including complete or partial response. Quality of life and toxicity were assessed. Molecular analyses for proliferation markers, hormone-regulated genes, and wingless-related integration site pathway activation were performed at baseline and 3 months. RESULTS: A total of 57 patients were treated (21 endometrial cancer, 36 complex atypical hyperplasia). The median age was 48.0 years, and the median body mass index was 45.5 kg/m2. Of the 47 evaluable patients, 12-month response rate was 83% (90% credible interval, 72.7-90.3)-37 were complete responders (8 endometrial cancer; 29 complex atypical hyperplasia), 2 were partial responders (2 endometrial cancer), 3 had stable disease (2 endometrial cancer; 1 complex atypical hyperplasia), and 5 had progressive disease (3 endometrial cancer; 2 complex atypical hyperplasia). After stratification for histology, the response rate was 90.6% for complex atypical hyperplasia and 66.7% for grade 1 endometrioid endometrial cancer. Notably, 4 patients (9.5%) experienced relapse after the initial response. Adverse events were mild, primarily irregular bleeding and cramping. Quality of life was not negatively affected. At 3 months, exogenous progesterone effect was present in 96.9% of responders (31 of 32) vs 25% of nonresponders (2 of 8) (P=.001). Nonresponders had higher baseline proliferation (Ki67) and lower dickkopf homolog 3 gene expression than responders (P=.023 and P=.030). Nonresponders had significantly different changes in secreted frizzled-related protein 1, frizzled class receptor 8, and retinaldehyde dehydrogenase 2 compared with responders. CONCLUSION: The levonorgestrel intrauterine device has a substantial activity in complex atypical hyperplasia and grade 1 endometrioid endometrial cancer, with a modest proportion demonstrating upfront progesterone resistance. Potential biomarkers were identified that may correlate with resistance to therapy; further exploration is warranted.

In vivo imaging of cervical precancer using a low-cost and easy-to-use confocal microendoscope.

Cervical cancer incidence and mortality rates remain high in medically underserved areas. In this study, we present a low-cost (<$5,000), portable and user-friendly confocal microendoscope, and we report on its clinical use to image precancerous lesions in the cervix. The confocal microendoscope employs digital apertures on a digital light projector and a CMOS sensor to implement line-scanning confocal imaging. Leveraging its versatile programmability, we describe an automated aperture alignment algorithm to ensure clinical ease-of-use and to facilitate technology dissemination in low-resource settings. Imaging performance is then evaluated in ex vivo and in vivo pilot studies; results demonstrate that the confocal microendoscope can enhance visualization of nuclear morphology, contributing to significantly improved recognition of clinically important features for detection of cervical precancer.

Toward development of a large field-of-view cancer screening patch (CASP) to detect cervical intraepithelial neoplasia.

Cervical cancers are primarily diagnosed via colposcopy, in which the tissue is visually assessed by a clinician for abnormalities, followed by directed biopsies and histologic analysis of excised tissue. Optical biopsy technologies offer a less invasive method of imaging such that subcellular features can be resolved without removing tissue. These techniques, however, are limited in field-of-view by the distal end of the probe. We present a prototype that incorporates a rigid, machinable waveguide that is in direct contact with a fluorescently-labeled sample paired with a scanning fluorescent microscope. The system is capable of imaging large areas of tissue without the need to re-position the tissue-probe interface. A mosaicing algorithm was developed to quantify scanning shifts and stitch neighboring frames together to increase the field-of-view. Our prototype can yield a maximum axial resolution of <5 µm for individual frames and can produce mosaiced images with a field-of-view greater than 15 mm x 15 mm without sacrificing resolution. We validated the system with a 1951 USAF resolution target, fluorescent in vitro standards, and a patient study where ex vivo conization samples of squamous cervical epithelium were imaged. The results of the patient study indicate that architectural features of subcellular components could be detected and differentiated between normal tissue and precancerous lesions.

Low-cost, high-resolution imaging for detecting cervical precancer in medically-underserved areas of Texas.

OBJECTIVE: Cervical cancer rates in the United States have declined since the 1940's, however, cervical cancer incidence remains elevated in medically-underserved areas, especially in the Rio Grande Valley (RGV) along the Texas-Mexico border. High-resolution microendoscopy (HRME) is a low-cost, in vivo imaging technique that can identify high-grade precancerous cervical lesions (CIN2+) at the point-of-care. The goal of this study was to evaluate the performance of HRME in medically-underserved areas in Texas, comparing results to a tertiary academic medical center. METHODS: HRME was evaluated in five different outpatient clinical settings, two in Houston and three in the RGV, with medical providers of varying skill and training. Colposcopy, followed by HRME imaging, was performed on eligible women. The sensitivity and specificity of traditional colposcopy and colposcopy followed by HRME to detect CIN2+ were compared and HRME image quality was evaluated. RESULTS: 174 women (227 cervical sites) were included in the final analysis, with 12% (11% of cervical sites) diagnosed with CIN2+ on histopathology. On a per-site basis, a colposcopic impression of low-grade precancer or greater had a sensitivity of 84% and a specificity of 45% to detect CIN2+. While there was no significant difference in sensitivity (76%, p = 0.62), the specificity when using HRME was significantly higher than that of traditional colposcopy (56%, p = 0.01). There was no significant difference in HRME image quality between clinical sites (p = 0.77) or medical providers (p = 0.33). CONCLUSIONS: HRME imaging increased the specificity for detecting CIN2+ when compared to traditional colposcopy. HRME image quality remained consistent across different clinical settings.

Prevalence of high-grade anal dysplasia among women with high-grade lower genital tract dysplasia or cancer: Results of a pilot study.

OBJECTIVE: To estimate the prevalence of high-grade anal dysplasia in women with high-grade dysplasia or carcinoma of the cervix, vagina or vulva. METHODS: In this cross-sectional study, participants underwent anal cytology, anal HPV testing with Cervista HPV16/18 and high-resolution anoscopy (HRA). Patients with HSIL (high-grade squamous cell intraepithelial lesion) or greater on anal cytology or anal biopsy were referred to a colorectal surgery specialist for further evaluation. RESULTS: Seventy-five women were enrolled in the study, including 47 with cervical (cervix group), 10 with vaginal (vagina group), 15 with vulvar (vulva group), 1 with cervical and vaginal, and 2 with vulvar and vaginal disease. The median age in the cervix group (40 years (range 26-69)) was substantially younger than in the vagina (60 years (38-69)) and the vulva (59 years (36-75)) groups. Anal HSIL based on composite endpoints of the most severe cytology or histology result was diagnosed in 6 patients (8.0%). Anal cytology revealed HSIL in 2 (2.7%), atypical squamous cells of undetermined significance (ASCUS) in 12 (16.0%), low-grade squamous cell intraepithelial lesion (LSIL) in 2 (2.7%), and was normal in 59 (78.7%) patients. Anal HPV16/18 test was positive in 15 (20.0%), negative in 48 (64.0%) and insufficient in 12 (16.0%) patients. Of the 6 women with high-grade anal dysplasia, three (50%) had a positive anal HPV16/18 test. No case of anal cancer was observed. CONCLUSION: Our results suggest that the prevalence of anal HSIL is elevated among women with HPV-related lower genital tract dysplasia or cancer. To further support the inclusion of this high-risk group into screening guidelines for anal dysplasia, further studies are necessary to determine what screening strategy is suited to this population.

Prospective Randomized Biomarker Study of Metformin and Lifestyle Intervention for Prevention in Obese Women at Increased Risk for Endometrial Cancer.

Obesity increases risk of endometrial cancer through dysregulation of estrogen and insulin signaling. The primary aim of this study was to evaluate the impact of metformin or lifestyle intervention on endometrial proliferation in postmenopausal obese women. Secondary aims included evaluating obesity-related biomarkers and adverse events experienced. Obese, postmenopausal women with prediabetes were randomized into four groups for a 16-week intervention using a 2 (metformin 1700 mg/day vs. placebo) × 2 (lifestyle intervention vs. no lifestyle intervention) factorial design. Pre- and postintervention endometrial proliferation, anthropometrics, body composition, and serum biomarkers (sex hormones, sex hormone binding globulin, IGF-I, adiponectin, omentin, insulin, glucose, and others) were assessed. Data were analyzed with linear regression models and false-discovery rate correction. Of 576 women approached for the study, 52 attended initial screening, 29 were eligible and randomized, and 26 completed the study. Lifestyle intervention resulted in significant loss of weight (-4.23 kg, P = 0.006) and total fat mass (-3.23 kg, P < 0.001). Participants receiving metformin lost 3.43 kg of weight (P = 0.023), but this was not statistically significant after multiple comparisons adjustment controlling false-discovery rate to 10%. Endometrial proliferation was low at baseline (mean 7.1%) and remained unchanged by 16 weeks, but included substantial variability. Metformin and lifestyle intervention produced minor changes to serum biomarkers. Lifestyle intervention produced the most significant changes in weight and body composition. While it is known that obese postmenopausal women are at increased risk for endometrial cancer, improved biomarkers are needed to stratify risk and test prevention strategies, particularly at the endometrial tissue level. Cancer Prev Res; 11(8); 477-90. ©2018 AACR.

Gynecologic cancer survivor preferences for long-term surveillance.

BACKGROUND: With ongoing healthcare reform and shrinking numbers of oncologists, appropriate triaging of gynecologic cancer survivor care is crucial. Input from patients is a necessary part of this task. The objective of this study was to assess the preferences of gynecologic cancer survivors for surveillance after the completion of treatment. METHODS: A 38-item questionnaire was developed and launched in conjunction with the Foundation for Women's Cancer (FWC). All women who registered as gynecologic cancer survivors with the FWC were invited to participate. Patients were asked about physician preferences for multiple symptoms and diagnoses, and when they felt comfortable transferring care out of their oncologists' offices. Analyses were performed with chi-square and logistic regression. RESULTS: Six hundred twenty four patients completed the questionnaire. Sixty six percent had ovarian cancer, and 86% were primarily treated by a gynecologic oncologist. Fifty seven percent of the respondents reported being unwilling to see a physician other than their oncologist for survivorship care at any time. Women age > 60 years were less willing to leave their oncologists for survivorship care at any time compared to younger women (OR 1.53 [95% CI 1.03-2.27], p = 0.03). Ovarian cancer survivors were also more likely to report a desire to stay with their oncologists compared with uterine cancer survivors (p < 0.001). With few exceptions, respondents preferred management of non-oncologic medical problems by their oncologists. CONCLUSIONS: Gynecologic cancer survivors prefer that their oncologists remain heavily involved in survivorship care. Reconciling patient needs with physician and financial constraints will be a challenge as the survivor population continues to grow.

Treatment of Low-Risk Endometrial Cancer and Complex Atypical Hyperplasia With the Levonorgestrel-Releasing Intrauterine Device.

OBJECTIVE: To assess efficacy of the levonorgestrel-releasing intrauterine device (LNG-IUD) for treatment of complex atypical hyperplasia or low-grade endometrial cancer. METHODS: This retrospective case series included all patients treated with the LNG-IUD for complex atypical hyperplasia or early-grade endometrial cancer from January 2003 to June 2013. Response rates were calculated and the association of response with clinicopathologic factors, including age, body mass index, and uterine size, was determined. RESULTS: Forty-six patients diagnosed with complex atypical hyperplasia or early-grade endometrial cancer were treated with the LNG-IUD. Of 32 evaluable patients at the 6-month time point, 15 had complex atypical hyperplasia (47%), nine had G1 endometrial cancer (28%), and eight had grade 2 endometrial cancer (25%). Overall response rate was 75% (95% CI 57-89) at 6 months; 80% (95% CI 52-96) in complex atypical hyperplasia, 67% (95% CI 30-93) in grade 1 endometrial cancer, and 75% (CI 35-97) in grade 2 endometrial cancer. Of the clinicopathologic features evaluated, there was a trend toward the association of lack of exogenous progesterone effect in the pathology specimen with nonresponse to the IUD (P=.05). Median uterine diameter was 1.3 cm larger in women who did not respond to the IUD (P=.04). CONCLUSION: Levonorgestrel-releasing IUD therapy for the conservative treatment of complex atypical hyperplasia or early-grade endometrial cancer resulted in return to normal histology in a majority of patients.

Project ECHO: A Telementoring Program for Cervical Cancer Prevention and Treatment in Low-Resource Settings.

Cervical cancer incidence and mortality rates are significantly higher in low- and middle-income countries compared with the United States and other developed countries. This disparity is caused by decreased access to screening, often coupled with low numbers of trained providers offering cancer prevention and treatment services. However, similar disparities are also found in underserved areas of the United States, such as the Texas-Mexico border, where cervical cancer mortality rates are 30% higher than in the rest of Texas. To address these issues, we have adopted the Project ECHO (Extension for Community Healthcare Outcomes) program, a low-cost telementoring model previously proven to be successful in increasing local capacity, improving patient management skills, and ultimately improving patient outcomes in rural and underserved areas. We use the Project ECHO model to educate local providers in the management of cervical dysplasia in a low-resource region of Texas and have adapted it to inform strategies for the management of advanced cervical and breast cancer in Latin America and sub-Saharan Africa. This innovative approach, using ECHO, is part of a larger strategy to enhance clinical skills and develop collaborative projects between academic centers and partners in low-resource regions.

Maternal and Fetal Outcomes After Therapy for Hodgkin or Non-Hodgkin Lymphoma Diagnosed During Pregnancy.

IMPORTANCE: The management of lymphoma diagnosed during pregnancy is controversial and has been guided largely by findings from case reports and small series. OBJECTIVE: To determine maternal and fetal outcomes of women diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) during pregnancy. DESIGN, SETTING, AND PARTICIPANTS: This retrospective analysis studied a cohort of 39 pregnant women diagnosed with HL and NHL (31 HL and 8 NHL) at a single specialized cancer institution between January 1991 and December 2014. MAIN OUTCOMES AND MEASURES: We examined data on disease and treatment characteristics, as well as maternal and fetal complications and outcomes. The Kaplan-Meier method was used to compare progression free survival (PFS) and overall survival (OS) according to receipt of antenatal therapy and other clinical factors. Univariate and multivariate analyses were performed by using Cox proportional hazard regression models to identify potential associations between clinical and treatment factors and survival. RESULTS: The median (range) age of the 39 women in the patient cohort was 28 (19-38) years; 32 women (82%) had stage I or II disease at diagnosis, and 13 had bulky disease. Three women electively terminated the pregnancy to allow immediate systemic therapy; of the remaining 36 women, 24 received antenatal therapy (doxorubicin based combination chemotherapy in 20 of 24 patients), and 12 deferred therapy until after delivery. Four women experienced miscarriage, all of whom had received antenatal systemic therapy and 2 during the first trimester. Delivery occurred at a median (range) of 37 (32-42) weeks and was no different based on receipt of antenatal (median [range], 37 [33-42] weeks) vs postnatal (median [range], 37 [32-42] weeks) therapy (P = .21). No gross fetal malformations or anomalies were detected. At a median (range) follow-up time of 67.9 (8.8-277.5) months since the diagnosis of lymphoma, 5-year rates of PFS and OS were 74.7% and 82.4%, respectively; these rates did not differ according to timing of therapy. On univariate analysis, bulky disease (>10 cm), extranodal nonbone marrow involvement, and poor performance status (Eastern Cooperative Oncology Group score, ≥2) predicted increased risk of disease progression. On multivariate analysis, extranodal nonbone marrow disease and performance status remained significant for both PFS and OS. CONCLUSIONS AND RELEVANCE: Systemic therapy given for lymphoma after the first trimester of pregnancy is likely safe and results in acceptable maternal and fetal outcomes.

Avoidable tragedies: Disparities in healthcare access among medically underserved women diagnosed with cervical cancer.

BACKGROUND: The purpose was to identify barriers including logistical and health belief correlates of late stage presentation of cervical cancer (CxCa) among medically underserved women presenting to a safety net health care system. METHODS: Women presenting with newly diagnosed CxCa were asked to complete a detailed health belief survey that included questions about barriers to care and their knowledge of CxCa. All information was collected prior to initiating cancer treatment. Comparisons were made among women diagnosed at early stages of disease amendable to surgical treatment (≤IB1) and those diagnosed at a stage requiring local-regional or systemic/palliative treatment (≥IB2). RESULTS: Among the 138 women, 21.7% were diagnosed with ≤lB1 disease, while 78.3% were diagnosed with ≥IB2 disease. Late-stage diagnosis was associated with a greater number of emergency room (ER) visits (p<.001) and blood transfusions (p<.001) prior to diagnosis. Compared to 88% with ≤lB1 disease, only 53% of patients with ≥IB2 disease had a car (p=.003). Women with ≥IB2 disease were more likely to be without a primary care provider (75.0% vs. 42.3%, p=.001). CONCLUSION: Access to transportation and lack of a regular primary care provider or a medical home are associated with late-stage of CxCa at diagnosis. Many medically underserved women continue to use the ER as their primary source of health care, and as a result their CxCa is diagnosed in advanced stages, with higher medical costs and lower chances of cure. The lack of Medicaid expansion in Texas may result in a worsening of this situation.

High-Grade Cervical Dysplasia following Radiation Therapy for Invasive Cervical Cancer: A Report of Four Cases.

INTRODUCTION: The standard treatment for locally advanced cervical cancer is chemoradiation, with the majority of patients having a complete response to the therapy. The current surveillance recommendations from the Society of Gynecologic Oncology include annual cytology, with a small proportion of patients subsequently diagnosed with high-grade cervical dysplasia (CIN 2/3). To date, there is limited information regarding the optimal treatment and outcome for patients diagnosed with CIN 2/3. The current report describes the diagnosis, management and outcome of 4 patients diagnosed with CIN 2/3 following chemoradiation. CASE DESCRIPTION: We describe 4 patients who developed CIN 2/3 seven months to 8 years following radiation therapy for locally advanced cervical cancer. All 4 patients were asymptomatic and the abnormalities were first detected by a Pap test. Three of the patients were managed conservatively with observation, and the CIN 2/3 resolved without intervention. One patient underwent 2 cervical conizations followed by a hysterectomy with no residual dysplasia noted on the hysterectomy specimen. CONCLUSION: The majority of patients with recurrent cervical cancer after chemoradiation are symptomatic, and most cases are detected by a physical examination. The role of cytology, colposcopy and biopsies may be of limited value. Furthermore, the significance of the diagnosis of CIN 2/3 in patients previously treated with radiation therapy was not associated with recurrent disease in the 4 patients described. Our results suggest that cytology may be of limited value in detecting recurrence in patients following radiation therapy, even when CIN 2/3 is detected.