Single-tube four-target lateral flow assay detects human papillomavirus types associated with majority of cervical cancers.

Isothermal nucleic acid amplification methods have many advantages for use at the point of care. However, there is a lack of multiplexed isothermal amplification tests to detect multiple targets in a single reaction, which would be valuable for many diseases, such as infection with high-risk human papillomavirus (hrHPV). In this study, we developed a multiplexed loop-mediated isothermal amplification (LAMP) reaction to detect the three most common hrHPV types that cause cervical cancer (HPV16, HPV18, and HPV45) and a cellular control for sample adequacy. First, we characterized the assay limit of detection (LOD) in a real-time reaction with fluorescence readout; after 30 min of amplification the LOD was 100, 10, and 10 copies/reaction of HPV16, HPV18, and HPV45, respectively, and 0.1 ng/reaction of human genomic DNA (gDNA). Next, we implemented the assay on lateral flow strips, and the LOD was maintained for HPV16 and HPV18, but increased to 100 copies/reaction for HPV45 and to 1 ng/reaction for gDNA. Lastly, we used the LAMP test to evaluate total nucleic acid extracted from 38 clinical samples; compared to qPCR, the LAMP test had 89% sensitivity and 95% specificity. When integrated with sample preparation, this multiplexed LAMP assay could be useful for point-of-care testing.

A Comprehensive Program to Improve Treatment of Precancerous Cervical Lesions in the Rio Grande Valley of Texas.

OBJECTIVE: To assess the impact of a multicomponent intervention in women with cervical dysplasia who were treated with loop electrosurgical excision procedure (LEEP), as well as the time between colposcopy and treatment. DESIGN: Retrospective cohort study. INTERVENTION: Clinic participation in a multicomponent cervical cancer prevention program that included community outreach, patient in-reach, and navigation, as well as provider capacity building with in-person training and ongoing telementoring through Project ECHO. MAIN OUTCOME MEASURES: Medical records were reviewed to evaluate women with cervical dysplasia undergoing treatment with LEEP within 90 days of colposcopy, as well as time between colposcopy and treatment. Baseline data from year 1 were compared with each subsequent year of implementation. Additional variables examined included patient's age, history of abnormal screening results, and percentage of families living below poverty line based on county of residence, parity, and clinic site. We performed logistic regression and multiple linear regression analyses to assess the programmatic impact in the outcomes of interest by year of program implementation. RESULTS: A total of 290 women were included in the study. The proportion of women undergoing treatment within 90 days of colposcopy increased from 76.2% at baseline to 91.3% in year 3 and 92.9% in year 4 of program implementation. The odds of undergoing treatment within 90 days were 5.11 times higher in year 4 of program implementation than at baseline. The mean time between colposcopy and LEEP decreased from 62 days at baseline to 45 days by year 4 of program implementation. CONCLUSIONS: Implementation of our multicomponent cervical cancer prevention program increased the proportion of women undergoing LEEP within 90 days of colposcopy and decreased the time between colposcopy and LEEP. This program has the potential to support cervical cancer prevention efforts and could be implemented in other low-resource settings.

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.

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.

Cervical lesion assessment using real-time microendoscopy image analysis in Brazil: The CLARA study.

We conducted a prospective evaluation of the diagnostic performance of high-resolution microendoscopy (HRME) to detect cervical intraepithelial neoplasia (CIN) in women with abnormal screening tests. Study participants underwent colposcopy, HRME and cervical biopsy. The prospective diagnostic performance of HRME using an automated morphologic image analysis algorithm was compared to that of colposcopy using histopathologic detection of CIN as the gold standard. To assess the potential to further improve performance of HRME image analysis, we also conducted a retrospective analysis assessing performance of a multi-task convolutional neural network to segment and classify HRME images. One thousand four hundred eighty-six subjects completed the study; 435 (29%) subjects had CIN Grade 2 or more severe (CIN2+) diagnosis. HRME with morphologic image analysis for detection of CIN Grade 3 or more severe diagnoses (CIN3+) was similarly sensitive (95.6% vs 96.2%, P = .81) and specific (56.6% vs 58.7%, P = .18) as colposcopy. HRME with morphologic image analysis for detection of CIN2+ was slightly less sensitive (91.7% vs 95.6%, P < .01) and specific (59.7% vs 63.4%, P = .02) than colposcopy. Images from 870 subjects were used to train a multi-task convolutional neural network-based algorithm and images from the remaining 616 were used to validate its performance. There were no significant differences in the sensitivity and specificity of HRME with neural network analysis vs colposcopy for detection of CIN2+ or CIN3+. Using a neural network-based algorithm, HRME has comparable sensitivity and specificity to colposcopy for detection of CIN2+. HRME could provide a low-cost, point-of-care alternative to colposcopy and biopsy in the prevention of cervical cancer.

Pelvic fractures and changes in bone mineral density after radiotherapy for cervical, endometrial, and vaginal cancer: A prospective study of 239 women.

BACKGROUND: Advances in radiotherapy (RT) have led to improved oncologic outcomes for women with gynecologic cancers; however, the long-term effects and survivorship implications need further evaluation. The purpose of this study was to determine the incidence of pelvic fractures and changes in bone mineral density (BMD) after pelvic RT. METHODS: Two hundred thirty-nine women who had pelvic RT for cervical, endometrial, or vaginal cancer between 2008 and 2015 were prospectively studied. BMD scans and biomarkers of bone turnover were obtained at the baseline and 3 months, 1 year, and 2 years after RT. Imaging studies were assessed for pelvic fractures for up to 5 years. Patients with osteopenia, osteoporosis, or pelvic fractures at any point were referred to the endocrinology service for evaluation and treatment. RESULTS: The median age at diagnosis was 51 years; 132 patients (56%) were menopausal. The primary diagnoses were cervical (63.6%), endometrial (30.5%), and vaginal cancer (5.9%). Sixteen patients (7.8%; 95% confidence interval, 4.5%-12.4%) had pelvic fractures with actuarial rates of 3.6%, 12.7%, and 15.7% at 1, 2, and 3 years, respectively. Fractures were associated with baseline osteoporosis (P < .001), higher baseline bone-specific alkaline phosphatase (P < .001), and older age (P = .007). The proportion of patients with osteopenia/osteoporosis increased from 50% at the baseline to 58%, 59%, and 70% at 3 months, 1 year, and 2 years, respectively. CONCLUSIONS: A high proportion of women had significant decreases in BMD after pelvic RT, with 7.8% diagnosed with a pelvic fracture. BMD screening and pharmacologic intervention should be strongly considered for these high-risk women.

The Capulana study: a prospective evaluation of cervical cancer screening using human papillomavirus testing in Mozambique.

BACKGROUND: Cervical cancer is the leading cause of cancer and related deaths among women in Mozambique. There is limited access to screening and few trained personnel to manage women with abnormal results. Our objective was to implement cervical cancer screening with human papillomavirus (HPV) testing, with navigation of women with abnormal results to appropriate diagnostic and treatment services. METHODS: We prospectively enrolled women aged 30-49 years living in Maputo, Mozambique, from April 2018 to September 2019. All participants underwent a pelvic examination by a nurse, and a cervical sample was collected and tested for HPV using the careHPV test (Qiagen, Gaithersburg, Maryland, USA). HPV positive women were referred for cryotherapy or, if ineligible for cryotherapy, a loop electrosurgical excision procedure. Women with findings concerning for cancer were referred to the gynecologic oncology service. RESULTS: Participants (n=898) had a median age of 38 years and 20.3% were women living with the human immunodeficiency virus. HPV positivity was 23.7% (95% confidence interval 21.0% to 26.6%); women living with human immunodeficiency virus were twice as likely to test positive for HPV as human immunodeficiency virus negative women (39.2% vs 19.9%, p<0.001). Most HPV positive women (194 of 213, 91.1%) completed all steps of their diagnostic work-up and treatment. Treatment included cryotherapy (n=158, 77.5%), loop electrosurgical excision procedure (n=30, 14.7%), or referral to a gynecologist or gynecologic oncologist (n=5, 2.5%). Of eight invasive cervical cancers, 5 (2.8%) were diagnosed in women living with human immunodeficiency virus and 3 (0.4%) in human immunodeficiency virus negative women (p=0.01). CONCLUSION: Cervical cancer screening with HPV testing, including appropriate follow-up and treatment, was feasible in our study cohort in Mozambique. Women living with human immunodeficiency virus appear to be at a significantly higher risk for HPV infection and the development of invasive cervical cancer than human immunodeficiency virus negative women.

Cervical cancer screening abnormalities in immunosuppressed renal transplant women: case-control study in Southern Brazil.

PURPOSE: To evaluate the prevalence of cervical pre-malignancies in the cervical cytology of female renal transplant recipients (RTR) and compare to immunocompetent patients. METHODS: A prospective case-control study of 165 RTR (cases) and 372 immunocompetent women (controls) was carried out from May 2015 to August 2016. The participants completed a questionnaire with demographic characteristics, habits, reproductive history, and information about the renal transplant. Cervical cytology samples were collected at their visit for cervical cancer screening. Relevant medical history was obtained from medical records and previous cervical cytology results were retrieved: from the time of kidney transplantation to the beginning of this study for RTR and all collected throughout life for controls. RESULTS: The mean age was similar between groups (42.6 ± 11.4 vs. 41.8.2 ± 11.1 years, p = 0.447). Considering cervical cytology collected since the kidney transplant, RTR had three times higher rates of abnormal cervical cytology test (24.8% of RTR vs. 6.3% for controls), and the abnormalities were more frequent (p < 0.001) for low squamous intraepithelial lesion (LSIL) (n = 23, 13.9%) and high squamous intraepithelial lesion (HSIL) (n = 9, 5.5%). Cervical cytology collected during the study had normal results in 152 RTR (92.1%) vs. 326 controls (93.9%) (p > 0.05). When the altered results were broken down, a higher frequency of LSIL could be seen in RTR (3.6% vs 0.0%, p = 0.008). CONCLUSION: RTR had significantly higher rates of cervical cytology abnormalities comparing to the control group and most of it was composed of LSIL.

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.

Perineural invasion (PNI) in vulvar carcinoma: A review of 421 cases.

OBJECTIVES: To evaluate the prevalence and associated prognostic indicators in patients with vulvar carcinoma with and without evidence of perineural invasion (PNI). METHODS: A retrospective review identified 421 patients with invasive vulvar carcinoma evaluated at a single institution between 1993 and 2011. Medical records were reviewed for demographic data, pathologic information and presence or absence of PNI, treatment type, and recurrence/outcome information. Variables were compared between patients with PNI to those without PNI. RESULTS: Of the 421 patients included in the study, 32 (7.6%) had tumors with PNI. There were no significant differences in age, race/ethnicity, smoking history, histologic subtype, or grade between the group of patients with PNI and the group without PNI. The group with PNI was more likely to have lichen sclerosus (25.0% vs. 15.4%, p = 0.024), stage III/IV disease (59.4% vs. 36.0%, p = 0.007), lymph node involvement (50.0% vs. 21.6%, p = 0.002), and lymphovascular space invasion (LVSI) (53.1% vs. 15.9%, p < 0.001). A higher proportion of patients in the PNI group underwent primary or adjuvant radiation therapy (68.8% vs. 45.0%, p = 0.016). The median follow-up was 67.1 months (range < 1.0 to 284.3). Patients with PNI had significantly shorter overall survival (OS), median 25.5 vs. 94.3 months (p < 0.001), and progression-free survival (PFS), median 17.5 vs. 29.0 months (p = 0.004). After adjusting for stage, patients with PNI had a greater risk for death and progression (OS: hazard ratio, 2.71; p < 0.001; PFS: hazard ratio, 1.64; p-value = 0.020). CONCLUSION: PNI should be considered an independent poor prognostic factor for patients with vulvar carcinoma, and should be included as part of the pathologic analysis.

Carcinoma of the Bartholin Gland: A Review of 33 Cases.

OBJECTIVE: Primary carcinoma of the Bartholin gland is a rare malignancy that accounts for approximately 5% of vulvar carcinomas. The aim of the study was to compare the outcomes of women with primary Bartholin gland carcinoma (BGC) with those with non-Bartholin gland-related vulvar carcinoma. MATERIALS AND METHODS: A retrospective chart review of 429 patients with invasive vulvar carcinoma evaluated at a single institution between 1993 and 2011 was performed. Medical records were reviewed for demographic data, pathologic information, treatment type, and recurrence/outcome information. These variables were compared between patients with primary BGC and patients with non-Bartholin gland-related vulvar carcinoma. RESULTS: Thirty-three (7.7%) of the 429 patients with invasive vulvar carcinoma had primary carcinoma of the Bartholin gland. Twenty-nine patients (87.9%) had squamous cell histology and 4 patients (12.1%) had adenocarcinoma. When compared with non-Bartholin gland-related vulvar carcinoma, patients with primary BGC had a younger age at diagnosis (median, 57 vs 63 years; P = 0.045), had a higher rate of stage III/IV disease (60.6% vs 35.8%; P = 0.008), and were more likely to receive radiation therapy (78.8% vs 43.9%; P < 0.001). However, there were no significant differences between the 2 groups with regard to histologic subtype, lymphovascular space involvement, perineural invasion, positive margins, recurrence-free survival, or overall survival. CONCLUSIONS: Despite being diagnosed at a more advanced stage, patients with primary carcinoma of the Bartholin gland seem to have similar oncologic outcomes and survival rates to patients with non-Bartholin gland-related vulvar carcinoma.

Prevalence of human papillomavirus infection in pregnant versus non-pregnant women in Brazil.

PURPOSE: To investigate the prevalence of human papillomavirus (HPV) in cervical samples of pregnant and non-pregnant women in South-Brazil. METHODS: A prospective study of 91 pregnant and 92 non-pregnant women with no previous history of cervical dysplasia or cancer was carried out. Cervical samples for HPV testing and cytology were collected in each trimester of pregnancy and in the puerperium for pregnant women and at matched intervals for the non-pregnant women. All samples were analyzed through PCR with consensus primers GP5+/GP6+. Genotyping was performed using specific primers. To control for confounding factors, the analysis of multivariate logistic regression was applied. The measure of odds ratio (OR) and the 95 % confidence interval (95 % CI) were used. The level of statistical significance was set at 5 % (P ≤ 0.05). RESULTS: HPV DNA was detected in 23/91 (25.3 %) cervical samples from the pregnant women and in 12/92 (13 %) cervical samples from non-pregnant women (P = 0.035). There was a significant association among cervical HPV infection and young age, number of lifetime sexual partners, and the presence of abnormal cervical cytology. HPV16 and HPV18 were the viral types more frequently detected. Out of the 23 HPV-positive pregnant women, 17 (73.9 %) had normal cervical cytology. CONCLUSION: Our results suggest a higher prevalence of HPV infection in pregnant vs. non-pregnant women. This finding may be related to the relative immunosuppression observed in pregnant women, outlining the importance of the appropriate monitoring of the viral infection in this specific population.

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.

Conservative Treatment of Stage IA1 Cervical Carcinoma Without Lymphovascular Space Invasion: A 20-year Retrospective Study in Brazil.

PURPOSE: To evaluate recurrence rates and risk factors among women with stage IA1 cervical cancer without lymph vascular space invasion managed conservatively. METHODS: retrospective review of women with stage IA1 squamous cervical cancer who underwent cold knife cone or loop electrosurgical excision procedure, between 1994 and 2015, at a gynecologic oncology center in Southern Brazil. Age at diagnosis, pre-conization findings, conization method, margin status, residual disease, recurrence and survival rates were collected and analyzed. RESULTS: 26 women diagnosed with stage IA1 squamous cervical cancer without lymphovascular space invasion underwent conservative management and had at least 12 months follow-up. The mean follow-up was 44.6 months. The mean age at diagnosis was 40.9 years. Median first intercourse occurred at age 16 years, 11.5% were nulliparous and 30.8% were current or past tobacco smokers. There was one Human immunodeficiency virus positive patient diagnosed with cervical intraepithelial neoplasia grade 2 at 30 months after surgery. However, there were no patients diagnosed with recurrent invasive cervical cancer and there were no deaths due to cervical cancer or other causes in the cohort. CONCLUSION: Excellent outcomes were noted in women with stage IA1 cervical cancer without lymphovascular space invasion and with negative margins who were managed conservatively, even in a developing country.

OBJETIVO: Avaliar recidiva e seus fatores de risco em mulheres com câncer do colo do útero estádio IA1 sem invasão do espaço linfovascular tratadas conservadoramente. MéTODOS:: Estudo de coorte retrospectivo de pacientes com câncer do colo do útero IA1 escamoso submetidas a cone do colo do útero, entre 1994 e 2015, em um centro de ginecologia oncológica do sul do Brasil. Foram revisados e analisados idade no diagnóstico, achados pré-conização, método de conização, margens, doença residual, recorrência e sobrevida. RESULTADOS: 26 mulheres diagnosticadas com câncer do colo do útero estádio escamoso sem invasão do espaço linfovascular foram submetidas a tratamento conservador, com seguimento mínimo de 12 meses. O tempo médio de seguimento foi 44,6 meses. A média de idade no diagnóstico foi 40,9 anos. A primeira relação sexual ocorreu aos 16 anos (mediana), 11,5% eram nulíparas e 30,8% eram tabagistas atuais ou passadas. Houve um caso de recidiva de neoplasia intraepitelial cervical grau 2 aos 30 meses em uma paciente com vírus da imunodeficiência humana. Não houve pacientes diagnosticados com câncer de colo do útero invasor recorrente, e não houve mortes por câncer do colo do útero ou outras causas. CONCLUSãO:: Os resultados observados após tratamento conservador em mulheres com câncer cervical escamoso IA1 sem invasão do espaço linfovascular com margens negativas foram excelentes, mesmo em um país em desenvolvimento.

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.

A low-cost, paper-based hybrid capture assay to detect high-risk HPV DNA for cervical cancer screening in low-resource settings.

Cervical cancer is a leading cause of cancer death for women in low-resource settings. The World Health Organization recommends that cervical cancer screening programs incorporate HPV DNA testing, but available tests are expensive, require laboratory infrastructure, and cannot be performed at the point-of-care. We developed a two-dimensional paper network (2DPN), hybrid-capture, signal amplification assay and a point-of-care sample preparation protocol to detect high-risk HPV DNA from exfoliated cervical cells within an hour. The test does not require expensive equipment and has an estimated cost of <$3 per test without the need for batching. We evaluated performance of the paper HPV DNA assay with short synthetic and genomic HPV DNA targets, HPV positive and negative cellular samples, and two sets of clinical samples. The first set of clinical samples consisted of 16 biobanked, provider-collected cervical samples from a study in El Salvador previously tested with careHPV and subsequently tested in a controlled laboratory environment. The paper HPV DNA test correctly identified eight of eight HPV-negative clinical samples and seven of eight HPV-positive clinical samples. We then performed a field evaluation of the paper HPV DNA test in a hospital laboratory in Mozambique. Cellular controls generated expected results throughout field testing with fully lyophilized sample preparation and 2DPN reagents. When evaluated with 16 residual self-collected cervicovaginal samples previously tested by the GeneXpert HPV assay ("Xpert"), the accuracy of the HPV DNA paper test in the field was reduced compared to testing in the controlled laboratory environment, with positive results obtained for all eight HPV-positive samples as well as seven of eight HPV-negative samples. Further evaluation showed reduction in performance was likely due in part to increased concentration of exfoliated cells in the self-collected clinical samples from Mozambique compared with provider-collected samples from El Salvador. Finally, a formal usability assessment was conducted with users in El Salvador and Mozambique; the assay was rated as acceptable to perform after minimal training. With additional optimization for higher cell concentrations and inclusion of an internal cellular control, the paper HPV DNA assay offers promise as a low-cost, point-of-care cervical cancer screening test in low-resource settings.

Expanding Cervical Cancer Screening in Mozambique: Challenges Associated With Diagnosing and Treating Cervical Cancer.

PURPOSE: Mozambique has one of the highest burdens of cervical cancer globally. Treatment options are few as most women present with advanced disease, and there are limited trained health professionals and health care resources. The objective of this study was to describe the outcomes of women diagnosed with invasive cancer as part of the Mozambican women undergoing cervical cancer screening with human papillomavirus (HPV) testing in conjunction with family planning services (MULHER) study. MATERIALS AND METHODS: Women age 30-49 years were prospectively enrolled in the MULHER study and offered screening with primary HPV testing followed by treatment of screen-positive women with thermal ablation or excision as appropriate. Women with cervical examination findings suspicious for cancer were referred to one of the three gynecologic oncologists in the country. RESULTS: Between January 2020 and January 2023, 9,014 women underwent cervical cancer screening and 30 women were diagnosed with cervical cancer. In this cohort, four patients (13.3%) had early-stage disease, 18 (60.0%) had locally advanced disease, one (3.3%) had distant metastatic disease, and seven (23.3%) did not have staging information available. Five patients (16.6%) died without receiving oncologic treatment, and seven patients (23.3%) are still awaiting treatment. Of the remaining 18 patients, three (17.6%) underwent surgery and four (23.5%) received radiotherapy. Eleven (36.7%) patients received only chemotherapy. CONCLUSION: As cervical screening programs are implemented in low-resource settings, there will likely be an increase in the number of women diagnosed with invasive cervical cancer. Our results in Mozambique demonstrate the need to increase access to advanced surgery, radiation, and palliative care services.