Search

More common than cervical cancer, cervical intraepithelial neoplasia (CIN) represents a precursor lesion of cervical carcinoma, being associated with HPV infection. Due to the bidirectional relationship between HPV and estrogen and progesterone in pregnancy, most of the published data claim that precancerous lesions remain stable or even regress during pregnancy, although several studies have indicated the tendency of HSILs to persist. It is considered that pregnancy-related cervical precancerous lesions undergo a postpartum regression, due to stimulatory effects of the immune microenvironment. Due to the rarity of publications on this subject, we aimed to offer a concise overview of and new insights into the current knowledge regarding the pathogenesis, diagnosis, and evolution of pregnancy-associated precancerous lesions, as well as their impact upon gestation and fertility. [ABSTRACT FROM AUTHOR]

Abstract Background The World Health Organization has set ambitious goals to eliminate cervical cancer, necessitating evidence on increasing coverage and access to screening and treatment in high-burden areas. We implemented a pilot program to assess the feasibility of obtaining self-collected specimens for high-risk human papillomavirus (hr-HPV) testing in Nzulezo stilt village, a hard-to-reach community in Ghana, and inviting only hr-HPV-positive women to a central location for colposcopy and possible treatment. Subsequently, this study aimed to investigate the prevalence of hr-HPV infection and cervical lesions among the women and to explore factors potentially associated with hr-HPV infection among them. Methods This pilot community-based cross-sectional study utilized data from screening sessions held from 2 to 20 November 2021 with specimens collected by participants using Evalyn brushes. HPV DNA testing was performed using the Sansure MA-6000 platform, while visual inspection utilized the Enhanced Visual Assessment (EVA) mobile colposcope. Univariate and multivariable nominal logistic regression was employed to explore factors associated with hr-HPV positivity. Results Among 100 women screened (mean age, 43.6 ± 14.5 years), the overall hr-HPV prevalence rate was 39.0% (95% CI, 29.4–49.3). The prevalence rates of hr-HPV genotypes were stratified as follows: HPV16–8.0% (95% CI, 3.5–15.2), HPV18–5.0% (95% CI, 1.6–11.2), and other genotype(s) – 31.0% (95% CI, 22.1–41.0). Single-genotype infections with HPV16 and HPV18 were found in 4.0% (95% CI, 1.1–9.9) and 3.0% (95% CI, 0.6–8.5) of women, respectively. Mixed infections were observed in 1.0% (95% CI, 0.0–5.4) for HPV16 + 18, 3.0% (95% CI, 0.6–8.5) for HPV16 + other type(s), and 1.0% (95% CI, 0.0–5.4) for HPV18 + other type(s). The prevalence of cervical lesions among hr-HPV-positive women screened via colposcopy was 11.4% (95% CI, 3.2–26.7). In the multivariable model, reliance on other sources for medical bill payment was associated with hr-HPV infection (aOR, 0.20; 95% CI, 0.04–0.93), whereas age was not (aOR, 1.02; 95% CI, 0.99–1.05). Conclusions A high hr-HPV infection prevalence was recorded among the women. Utilizing technologies such as self-sampling, HPV DNA testing, and mobile colposcopy enables screening and treatment in remote and hard-to-reach communities where access to cervical cancer screening and treatment would otherwise be limited. Further research is warranted to assess the value and scalability of this approach in similar remote areas and its potential implementation in future programs.

Abstract Background Cervical cancer continues to disproportionately burden women in low/middle-income countries like Ghana. We examined treatment patterns and histopathological outcomes among women screened using visual inspection with acetic acid (VIA) and/or mobile colposcopy who subsequently underwent thermal ablation, large loop excision of the transformation zone (LLETZ), or cold knife conization at the Cervical Cancer Prevention and Training Centre, Battor. We also assessed the prevalence of cervical intraepithelial neoplasia 2+ (CIN2+) or micro-invasive disease and their associated factors for women who underwent excisional treatments. The treatment choices for cervical precancerous lesions suitable for resource-limited settings have also been described from the perspective of a center that manages a heterogenous population. Methods We conducted an analysis of secondary data collected between June 2016 and June 2023 among women with positive findings on VIA or mobile colposcopy who subsequently underwent thermal ablation or large loop excision of the transformation zone (LLETZ). The prevalence of histopathology outcomes, including no dysplasia, CIN1 − 3, and micro-invasive disease, were estimated with 95% confidence intervals (CIs). Factors associated with histopathological findings were modeled using multinomial logistic regression. Results For the study period, 14 (10.6%) of the total 132 participants underwent cervical lesion treatment at outreach locations, all via thermal ablation. The remaining 118 (89.4%) were treated at the Catholic Hospital, Battor using LLETZ (n = 66, 55.9%), thermal ablation (n = 51, 43.2%), and cold knife conization (n = 1, 0.9%). Among 65 women with histopathology reports, the most frequent histopathological finding was no dysplasia (47.7%; 95% CI, 35.1 − 60.5), followed by CIN2 and CIN3 (20.0%; 95% CI, 11.1 − 31.8 each), CIN1 (7.7%; 95% CI, 2.5 − 17.0) and micro-invasion (4.6%; 95% CI, 1.0 − 12.9). Those with micro-invasive disease were significantly older than those with CIN1, CIN2, and CIN3 (p = 0.036, 0.022, 0.009, respectively), but not significantly older than those who showed no dysplasia (p = 0.088). For each unit increase in age, the likelihood of CIN3 was relatively significantly reduced compared to no dysplasia (crude relative risk ratio [RRR] = 0.93; 95% CI, 0.86 − 0.99). This association was neither observed with the remaining histopathological groups nor for parity and persisted after controlling for parity (adjusted RRR = 0.92; 95% CI, 0.85 − 0.99; p = 0.025). Conclusion This paper largely demonstrates treatment options available to women and practitioners in LMICs. The high combined prevalence of high-grade precancerous lesions and micro-invasive disease underscores the need to increase cervical cancer awareness that would enhance screening attendance and hasten efforts at moving from opportunistic to organized screening in Ghana. This will enhance early cervical lesion detection and treatment, while simultaneously re-evaluating and cutting down on unnecessary treatment.

Human papilloma virus (HPV) infections vary in their oncogenic potential, and whether an infection progresses to cervical intraepithelial neoplasia (CIN) also depends on the immune response. Therefore, the aim of the present study was to explore biomarkers related to the immune system and cell proliferation, in combination with HPV classified as having high (HOP) or low oncogenic potential (LOP), that can possibly guide a more accurate identification of women following cervical cancer screening programmes in need for immediate follow-up with a biopsy. A next-generation sequencing transcriptomic immune profile analysis applied to 28 persistent CIN3 lesions and 14 normal biopsies identified four genes, the immune markers ARG1 and HLA-DQB2 and the tumour markers CDKN2A and KRT7, as possible markers for differentiating between CIN3 and normal tissue. To validate these findings, analysis of the relative gene expression of these markers by use of reverse transcriptase real-time quantitative polymerase chain reaction was performed in an independent cohort of 264 (82 normal, 64 CIN1, and 118 CIN2/CIN3) biopsies, and the data were combined with information on the HOP- or LOP-HPV identified in the biopsies. Statistical analysis was performed with receiver operating characteristic curves, reporting area under the curve (AUC) with 95% confidence intervals (CIs), and logistic regression. Statistically significantly higher median expression levels of CDKN2A (p < 0.001) and KRT7 (p = 0.045) and significantly lower expression of ARG1 (p = 0.012) were found in biopsies with HOP-HPV infections, with no difference detected for HLA-DQB2 (p = 0.82). Models using expression levels of CDKN2A (AUC, 0.91; 95% CI, 0.86–0.95), KRT7 (0.86, 0.81–0.91), or ARG1 (0.78, 0.70–0.85) together with HOP/LOP-HPV class were significantly better than HPV class alone (0.72, 0.66–0.79) in discriminating CIN2/3 versus CIN1 (p < 0.001, p < 0.001, and p = 0.014, respectively).

BackgroundCervical cancer is a leading cause of cancer-related deaths among women. However, in developing countries, the primary focus for cervical cancer prevention and control remains on the timely detection and treatment of precancerous lesions. This study aims to evaluate the accuracy of colposcopic diagnosis of cervical intraepithelial lesions and analyze the factors influencing its accuracy.MethodsThis study collected data from 512 eligible patients who visited the gynecology outpatient clinic of the Second Hospital of Jilin University from January 2022 to August 2023. The final diagnosis was based on the highest grade observed in both biopsy pathology and postoperative pathology. A self-controlled, retrospective analysis was conducted to evaluate the accuracy of colposcopic diagnosis. Univariate analysis was used to assess the impact of factors such as menopausal status, duration of menopause, high-risk human papillomavirus (HR-HPV) genotypes, and transformation zone (TZ) types on the accuracy of colposcopic diagnosis of cervical lesions.ResultThe overall colposcopy diagnostic concordance rate was 78.71%. The concordance rates between the premenopausal and postmenopausal groups differed significantly (χ2 = 75.450, p

Abstract Background Low- and middle-income countries (LMICs) account for nearly 85% of the global cervical cancer burden, yet have the least access to high-performance screening. International guidelines recommend human papillomavirus testing (HPV) as primary screening, yet implementation is inhibited by the cost of HPV testing. Atila AmpFire® HPV Assay (AmpFire) is both affordable and easy to use, and offers individual genotyping. The objective of this study was to compare the performance of the AmpFire HPV assay to the Xpert® HPV assay in detection of both HPV and clinically significant cervical disease. Methods We utilized stored cervical specimens from a prospective cohort study of women living with human immunodeficiency virus (HIV) in Botswana conducted from May to July 2018. Positive and negative percent agreement was calculated for the AmpFire and Xpert assays, as was detection of high-grade cervical dysplasia. Results 63 stored cervical specimens had detectable DNA after thawing and were included in the analysis. The positive percent agreement was 91.2% (95%CI 76.3–98.1) and negative percent agreement was 79.3% (95% CI 60.3–92.0). Six cases positive by AmpFire but negative by Xpert were HPV genotypes 35, 52 (n = 2), 58, 68, and co-infection with HPV 45 and 68. Both Xpert and AmpFire assays detected HPV in all 10 samples of women who had high-grade cervical dysplasia. Conclusions The AmpFire HPV assay demonstrated excellent analytic performance in both detection of HPV and clinically significant cervical disease. AmpFire HPV is a promising option to increase access to affordable, type-specific HPV screening for cervical cancer in LMICs.

Abstract Background Though obesity has been said to be associated with a number of malignancies including cervical cancer, its association with cervical intraepithelial neoplasia (CIN) is still a contentious issue. This study was designed to determining the prevalence and association between obesity and CIN. Methods This was an unmatched case control study, involving women with cervical intraepithelial neoplasia (cases) and those negative for intraepithelial lesions or malignancy (controls) at the cervical cancer clinic of Mbarara Regional Referral Hospital, in south-western Uganda, between April and November 2022. Cases and controls provided written informed consent and were recruited in a ratio of 1:1. Cases were identified by visual inspection with acetic acid (VIA) and subsequent confirmation with cytology and/or histology. Demographic information was collected using an enrolment form and height, weight and waist circumference were recorded. We calculated body mass index (BMI) and identified obese women as those with body mass index of ≥ 30 kg/m2 from both case and control groups. Central obesity was defined as waist: height ration of ≥ 0.5. Data was analysed using STATA version 17. Categorical variables were analysed using proportions, chi-square and logistic regression analysis to determine association between obesity and CIN. Our level of statistical significance was set at ≤ 0.05. Results The prevalence of general and central obesity among cases was 25.5% (24/94) and 0% (0/94) respectively while the prevalence of general and central obesity among controls was 33.3% (37/111) and 0% (0/111) respectively. There was an increased prevalence of general obesity among women with low grade squamous intraepithelial lesions (LSIL). However, there was no statistically significant association between general obesity and CIN. Factors associated with general obesity included residing in Mbarara city (AOR 2.156, 95%CI 1.085–4.282, P-value 0.028), age group of 31–45 years (AOR 2.421, 95%CI 1.577–9.705, P-value 0.003) and ≥ 46 years (AOR 1.971, 95%CI 1.022–11.157, P-value 0.046). Conclusion We observed an increased prevalence of general obesity among women with LSIL. However, there was no association between obesity and CIN. Factors associated with general obesity included residing in Mbarara city, and being in the age groups of 31–40 and ≥ 46 years. This highlights the need to rethink management of CIN to control other non-communicable diseases that could arise due to general obesity.

Background: Studies on the clinical performance of p16/Ki-67 dual-staining in detecting cervical lesions by menopausal status were limited. Methods: 4364 eligible women were enrolled with valid p16/Ki-67, HR-HPV, and LBC test results, including 542 cancer and 217 CIN2/3 cases. The positivity rates of p16 and Ki-67 single staining and p16/ Ki-67 dual-staining were analyzed by different pathological grades and age groups. The sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV) of each test in different subgroups were calculated and compared. Results: P16/Ki-67 dual-staining positivity increased with histopathological severity in premenopausal and postmenopausal women (P < 0.05), while no increasing trends of individual expression of p16 single staining and Ki-67 single staining were observed in postmenopausal women. P16/Ki-67 showed higher SPE (88.09% vs. 81.91%, P < 0.001) and PPV (33.8% vs. 13.18%, P < 0.001) in detecting CIN2/3, and higher SEN (89.97% vs. 82.61%, P = 0.012) and SPE (83.22% vs. 79.89%, P = 0.011) in detecting cancer in premenopausal women than postmenopausal women. For triaging the HR-HPV+ population to identify CIN2/3, p16/Ki-67 performed comparably to LBC in the premenopausal women, and showed higher PPV (51.14% vs. 23.08%, P < 0.001) in premenopausal than postmenopausal women. For triaging ASC-US/LSIL population, p16/Ki-67 demonstrated higher SPE and lower colposcopy referral rate than HR-HPV in both premenopausal and postmenopausal women. Conclusions: Expressions of p16/Ki-67 dual-staining between premenopausal and postmenopausal women are varied. P16/Ki-67 performs better in detecting cervical lesions in premenopausal women. For triaging, p16/Ki-67 is suitable for HR-HPV+ women, especially premenopausal women, to identify CIN2/3 and women with ASC-US/LSIL. [ABSTRACT FROM AUTHOR]

High-risk, cancer-causing human papillomavirus (HPV) types are associated with cervical precancer and cancer. A high proportion of high-risk HPV precancer lesions undergo immune-mediated regression. The purpose of this study was to determine if the tissue microenvironment of HPV16 and 18 (HPV16/18) cervical intraepithelial neoplasia grade 2 lesions differed from other high-risk types (HPV 'other'). Consistent with other studies, we found that progression to higher-grade disease was more frequent in HPV16/18 lesions when compared with HPV 'other' lesions. HPV16/18 lesions were significantly more likely to be indoleamine 2,3,-dioxygenase 1 (IDO1)-positive and were associated with reduced CD8 and FoxP3 T cells in the lesion. In the stroma, reduced Tbet- and CD32-positive cells and increased Blimp1-positive cells were significantly associated with HPV16/18 lesions when compared with HPV 'other' types. On analysis of the IDO1-positive tissues, lesional IDO1 was associated with significantly decreased numbers of CD4-, CD8-, and FoxP3-positive cells in the stroma compared with IDO1-negative tissues. These data suggest that IDO1 expression may impair infiltration of CD4, CD8, and FoxP3 cells into the stroma beneath the precancer lesion. Increased expression of IDO1 may contribute to immune avoidance and an increased frequency of disease progression in HPV16- and 18-positive lesions. [ABSTRACT FROM AUTHOR]

Abstract Background Colposcopic examination with biopsy is the standard procedure for referrals with abnormal cervical cancer screening results; however, the decision to biopsy is controvertible. Having a predictive model may help to improve high-grade squamous intraepithelial lesion or worse (HSIL+) predictions which could reduce unnecessary testing and protecting women from unnecessary harm. Methods This retrospective multicenter study involved 5,854 patients identified through colposcopy databases. Cases were randomly assigned to a training set for development or to an internal validation set for performance assessment and comparability testing. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to reduce the number of candidate predictors and select statistically significant factors. Multivariable logistic regression was then used to establish a predictive model which generates risk scores for developing HSIL+. The predictive model is presented as a nomogram and was assessed for discriminability, and with calibration and decision curves. The model was externally validated with 472 consecutive patients and compared to 422 other patients from two additional hospitals. Results The final predictive model included age, cytology results, human papillomavirus status, transformation zone types, colposcopic impressions, and size of lesion area. The model had good overall discrimination when predicting HSIL + risk, which was internally validated (Area Under the Curve [AUC] of 0.92 (95%CI 0.90–0.94)). External validation found an AUC of 0.91 (95%CI 0.88–0.94) across the consecutive sample, and 0.88 (95%CI 0.84–0.93) across the comparative sample. Calibration suggested good coherence between predicted and observed probabilities. Decision curve analysis also suggested this model would be clinically useful. Conclusion We developed and validated a nomogram which incorporates multiple clinically relevant variables to better identify HSIL + cases during colposcopic examination. This model may help clinicians determining next steps and in particular, around the need to refer patients for colposcopy-guided biopsies.

Abstract Introduction Accessible planning tools tailored for low-and middle-income countries can assist decision makers in comparing implementation of different cervical cancer screening approaches and treatment delivery scenarios in settings with high cervical cancer burden. Methods The Cervical Precancer Planning Tool (CPPT) was developed by PATH for users to explore and compare the accuracy of screening approaches, what treatment equipment to procure, and how best to deploy treatment equipment in a given country. The CPPT compares four screening approaches: 1) visual inspection with acetic acid (VIA), 2) HPV testing, 3) HPV testing followed by a VIA triage, and 4) HPV testing followed by an enhanced triage test. Accuracy of screening outcomes (e.g., true positives, false positives) is based on published sensitivity and specificity of tests to detect cervical precancerous lesions. The CPPT compares five scenarios for deploying ablative treatment equipment: 1) cervical precancer equipment at every location a woman is screened (single visit approach), 2) equipment only at a hospital level, 3) a single unit of equipment in each district, 4) allowing two districts to share a single unit of equipment, and 5) equipment placed at select district hospitals paired with mobile outreach. Users can customize the CPPT by adjusting pre-populated baseline values and assumptions, including population estimates, screening age range, screening frequency, HPV and HIV prevalence, supply costs, and health facility details. Results The CPPT generates data tables and graphs that compare the results of implementing each of the four screening and five treatment scenarios disaggregated by HIV status. Outputs include the number and outcomes of women screened, cost of each screening approach, provider time and cost saved by implementing self-sampling for HPV testing, number of women treated, treatment equipment needed by type, and the financial and economic costs for each equipment deployment scenario. Conclusion The CPPT provides practical information and data to compare tradeoffs of patient access and screening accuracy as well as efficient utilization of equipment, skilled personnel, and financial resources. Country decision makers can use outputs from the CPPT to guide the scale-up of cervical cancer screening and treatment while optimizing limited resources.

Background: Low- and middle-income countries (LMICs) account for nearly 85% of the global cervical cancer burden, yet have the least access to high-performance screening. International guidelines recommend human papillomavirus testing (HPV) as primary screening, yet implementation is inhibited by the cost of HPV testing. Atila AmpFire® HPV Assay (AmpFire) is both affordable and easy to use, and offers individual genotyping. The objective of this study was to compare the performance of the AmpFire HPV assay to the Xpert® HPV assay in detection of both HPV and clinically significant cervical disease. Methods: We utilized stored cervical specimens from a prospective cohort study of women living with human immunodeficiency virus (HIV) in Botswana conducted from May to July 2018. Positive and negative percent agreement was calculated for the AmpFire and Xpert assays, as was detection of high-grade cervical dysplasia. Results: 63 stored cervical specimens had detectable DNA after thawing and were included in the analysis. The positive percent agreement was 91.2% (95%CI 76.3–98.1) and negative percent agreement was 79.3% (95% CI 60.3–92.0). Six cases positive by AmpFire but negative by Xpert were HPV genotypes 35, 52 (n = 2), 58, 68, and co-infection with HPV 45 and 68. Both Xpert and AmpFire assays detected HPV in all 10 samples of women who had high-grade cervical dysplasia. Conclusions: The AmpFire HPV assay demonstrated excellent analytic performance in both detection of HPV and clinically significant cervical disease. AmpFire HPV is a promising option to increase access to affordable, type-specific HPV screening for cervical cancer in LMICs. [ABSTRACT FROM AUTHOR]

Background: Though obesity has been said to be associated with a number of malignancies including cervical cancer, its association with cervical intraepithelial neoplasia (CIN) is still a contentious issue. This study was designed to determining the prevalence and association between obesity and CIN. Methods: This was an unmatched case control study, involving women with cervical intraepithelial neoplasia (cases) and those negative for intraepithelial lesions or malignancy (controls) at the cervical cancer clinic of Mbarara Regional Referral Hospital, in south-western Uganda, between April and November 2022. Cases and controls provided written informed consent and were recruited in a ratio of 1:1. Cases were identified by visual inspection with acetic acid (VIA) and subsequent confirmation with cytology and/or histology. Demographic information was collected using an enrolment form and height, weight and waist circumference were recorded. We calculated body mass index (BMI) and identified obese women as those with body mass index of ≥ 30 kg/m2 from both case and control groups. Central obesity was defined as waist: height ration of ≥ 0.5. Data was analysed using STATA version 17. Categorical variables were analysed using proportions, chi-square and logistic regression analysis to determine association between obesity and CIN. Our level of statistical significance was set at ≤ 0.05. Results: The prevalence of general and central obesity among cases was 25.5% (24/94) and 0% (0/94) respectively while the prevalence of general and central obesity among controls was 33.3% (37/111) and 0% (0/111) respectively. There was an increased prevalence of general obesity among women with low grade squamous intraepithelial lesions (LSIL). However, there was no statistically significant association between general obesity and CIN. Factors associated with general obesity included residing in Mbarara city (AOR 2.156, 95%CI 1.085–4.282, P-value 0.028), age group of 31–45 years (AOR 2.421, 95%CI 1.577–9.705, P-value 0.003) and ≥ 46 years (AOR 1.971, 95%CI 1.022–11.157, P-value 0.046). Conclusion: We observed an increased prevalence of general obesity among women with LSIL. However, there was no association between obesity and CIN. Factors associated with general obesity included residing in Mbarara city, and being in the age groups of 31–40 and ≥ 46 years. This highlights the need to rethink management of CIN to control other non-communicable diseases that could arise due to general obesity. [ABSTRACT FROM AUTHOR]

Background: Colposcopic examination with biopsy is the standard procedure for referrals with abnormal cervical cancer screening results; however, the decision to biopsy is controvertible. Having a predictive model may help to improve high-grade squamous intraepithelial lesion or worse (HSIL+) predictions which could reduce unnecessary testing and protecting women from unnecessary harm. Methods: This retrospective multicenter study involved 5,854 patients identified through colposcopy databases. Cases were randomly assigned to a training set for development or to an internal validation set for performance assessment and comparability testing. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to reduce the number of candidate predictors and select statistically significant factors. Multivariable logistic regression was then used to establish a predictive model which generates risk scores for developing HSIL+. The predictive model is presented as a nomogram and was assessed for discriminability, and with calibration and decision curves. The model was externally validated with 472 consecutive patients and compared to 422 other patients from two additional hospitals. Results: The final predictive model included age, cytology results, human papillomavirus status, transformation zone types, colposcopic impressions, and size of lesion area. The model had good overall discrimination when predicting HSIL + risk, which was internally validated (Area Under the Curve [AUC] of 0.92 (95%CI 0.90–0.94)). External validation found an AUC of 0.91 (95%CI 0.88–0.94) across the consecutive sample, and 0.88 (95%CI 0.84–0.93) across the comparative sample. Calibration suggested good coherence between predicted and observed probabilities. Decision curve analysis also suggested this model would be clinically useful. Conclusion: We developed and validated a nomogram which incorporates multiple clinically relevant variables to better identify HSIL + cases during colposcopic examination. This model may help clinicians determining next steps and in particular, around the need to refer patients for colposcopy-guided biopsies. [ABSTRACT FROM AUTHOR]

ObjectiveRecent studies reported a lower human papillomavirus 16 (HPV16) prevalence in cervical precancer among African American than Caucasian women in the general population. We assessed this relationship in women with HIV.DesignWomen living with or at risk for HIV in the Women's Interagency HIV Study were followed semi-annually with Pap tests, colposcopy/histology (if indicated), and collection of cervicovaginal lavage samples for HPV testing by PCR. Racial and ethnic groups were defined using genomic Ancestry Informative Markers (AIMs).ResultsAmong 175 cases of cervical intraepithelial neoplasia 3 or worse (CIN-3+), 154 were diagnosed in women with HIV. African American (27%) and Hispanic (37%) cases were significantly less likely than Caucasian (62%) women to test positive for HPV16 (P = 0.01). In multivariate logistic regression models, these associations remained significant for African Americans (odds ratio = 0.13; 95% confidence interval (CI) 0.04-0.44; P = 0.001) but not Hispanics, after controlling for HIV status, CD4 count, history of AIDS, age, smoking, and sexual behavior. Limiting the analysis to women with HIV did not change the findings.ConclusionHPV16 prevalence is lower in African American compared with Caucasian women with HIV and cervical precancer, independent of immune status. Future studies to determine why these racial differences exist are warranted, and whether there are similar associations between race and invasive cervical cancer in women with HIV. Further, HPV types not covered by quadrivalent and bivalent vaccines may play an especially important role in cervical precancer among HIV-positive African American women, a possible advantage to using nonavalent HPV vaccine in this population.

Introduction: Accessible planning tools tailored for low-and middle-income countries can assist decision makers in comparing implementation of different cervical cancer screening approaches and treatment delivery scenarios in settings with high cervical cancer burden.Methods: The Cervical Precancer Planning Tool (CPPT) was developed by PATH for users to explore and compare the accuracy of screening approaches, what treatment equipment to procure, and how best to deploy treatment equipment in a given country. The CPPT compares four screening approaches: 1) visual inspection with acetic acid (VIA), 2) HPV testing, 3) HPV testing followed by a VIA triage, and 4) HPV testing followed by an enhanced triage test. Accuracy of screening outcomes (e.g., true positives, false positives) is based on published sensitivity and specificity of tests to detect cervical precancerous lesions. The CPPT compares five scenarios for deploying ablative treatment equipment: 1) cervical precancer equipment at every location a woman is screened (single visit approach), 2) equipment only at a hospital level, 3) a single unit of equipment in each district, 4) allowing two districts to share a single unit of equipment, and 5) equipment placed at select district hospitals paired with mobile outreach. Users can customize the CPPT by adjusting pre-populated baseline values and assumptions, including population estimates, screening age range, screening frequency, HPV and HIV prevalence, supply costs, and health facility details.Results: The CPPT generates data tables and graphs that compare the results of implementing each of the four screening and five treatment scenarios disaggregated by HIV status. Outputs include the number and outcomes of women screened, cost of each screening approach, provider time and cost saved by implementing self-sampling for HPV testing, number of women treated, treatment equipment needed by type, and the financial and economic costs for each equipment deployment scenario.Conclusion: The CPPT provides practical information and data to compare tradeoffs of patient access and screening accuracy as well as efficient utilization of equipment, skilled personnel, and financial resources. Country decision makers can use outputs from the CPPT to guide the scale-up of cervical cancer screening and treatment while optimizing limited resources. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is a leading cause of cancer-related deaths among women. However, in developing countries, the primary focus for cervical cancer prevention and control remains on the timely detection and treatment of precancerous lesions. This study aims to evaluate the accuracy of colposcopic diagnosis of cervical intraepithelial lesions and analyze the factors influencing its accuracy., Methods: This study collected data from 512 eligible patients who visited the gynecology outpatient clinic of the Second Hospital of Jilin University from January 2022 to August 2023. The final diagnosis was based on the highest grade observed in both biopsy pathology and postoperative pathology. A self-controlled, retrospective analysis was conducted to evaluate the accuracy of colposcopic diagnosis. Univariate analysis was used to assess the impact of factors such as menopausal status, duration of menopause, high-risk human papillomavirus (HR-HPV) genotypes, and transformation zone (TZ) types on the accuracy of colposcopic diagnosis of cervical lesions., Result: The overall colposcopy diagnostic concordance rate was 78.71%. The concordance rates between the premenopausal and postmenopausal groups differed significantly ( χ 2  = 75.450, p  < 0.05). The HPV16/18 positive group and the non 16/18 HR-HPV positive group also showed a significant difference in concordance rates ( χ 2  = 5.890, p  < 0.05). There were significant differences in concordance rates between TZ2 and TZ3 ( χ 2  = 10.585, p  < 0.05), as well as between TZ1 and TZ3 ( χ 2  = 14.607, p  < 0.05)., Conclusion: Factors such as menopausal status, duration of menopause, HR-HPV genotypes, and TZ types influence the accuracy of colposcopic diagnosis. Therefore, a comprehensive evaluation incorporating these factors should be performed in clinical practice to enhance diagnostic accuracy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chu, Chen, Liu, Zhou, Bao, Wang and Lin.)

High-risk, cancer-causing human papillomavirus (HPV) types are associated with cervical precancer and cancer. A high proportion of high-risk HPV precancer lesions undergo immune-mediated regression. The purpose of this study was to determine if the tissue microenvironment of HPV16 and 18 (HPV16/18) cervical intraepithelial neoplasia grade 2 lesions differed from other high-risk types (HPV ‘other’). Consistent with other studies, we found that progression to higher-grade disease was more frequent in HPV16/18 lesions when compared with HPV ‘other’ lesions. HPV16/18 lesions were significantly more likely to be indoleamine 2,3,-dioxygenase 1 (IDO1)-positive and were associated with reduced CD8 and FoxP3 T cells in the lesion. In the stroma, reduced Tbet- and CD32-positive cells and increased Blimp1-positive cells were significantly associated with HPV16/18 lesions when compared with HPV ‘other’ types. On analysis of the IDO1-positive tissues, lesional IDO1 was associated with significantly decreased numbers of CD4-, CD8-, and FoxP3-positive cells in the stroma compared with IDO1-negative tissues. These data suggest that IDO1 expression may impair infiltration of CD4, CD8, and FoxP3 cells into the stroma beneath the precancer lesion. Increased expression of IDO1 may contribute to immune avoidance and an increased frequency of disease progression in HPV16- and 18-positive lesions.

Simple Summary: There is an unmet clinical need for new methods to aid clinicians in the early detection of cervical cancer and precancer. Spectroscopic methods such as Raman spectroscopy can provide a rapid, label-free and nondestructive measurement of the biochemical fingerprint of cells, tissues and biofluids. This study aims to demonstrate the clinical utility of Raman spectroscopy for the identification of cervical precancer. Raman spectra were recorded from cervical smear samples (n = 662) and a classifier was developed based on histology. A classification accuracy of 91.3% was achieved in an independent blinded test set (n = 69), demonstrating the potential clinical utility of Raman spectroscopy. The mortality associated with cervical cancer can be reduced if detected at the precancer stage, but current methods are limited in terms of subjectivity, cost and time. Optical spectroscopic methods such as Raman spectroscopy can provide a rapid, label-free and nondestructive measurement of the biochemical fingerprint of a cell, tissue or biofluid. Previous studies have shown the potential of Raman spectroscopy for cervical cancer diagnosis, but most were pilot studies with small sample sizes. The aim of this study is to show the clinical utility of Raman spectroscopy for identifying cervical precancer in a large sample set with validation in an independent test set. Liquid-based cervical cytology samples (n = 662) (326 negative, 200 cervical intraepithelial neoplasia (CIN)1 and 136 CIN2+) were obtained as a training set. Raman spectra were recorded from single-cell nuclei and subjected to a partial least squares discriminant analysis (PLSDA). In addition, the PLSDA classification model was validated using a blinded independent test set (n = 69). A classification accuracy of 91.3% was achieved with only six of the blinded samples misclassified. This study showed the potential clinical utility of Raman spectroscopy with a good classification of negative, CIN1 and CIN2+ achieved in an independent test set. [ABSTRACT FROM AUTHOR]

Simon M Manga,1– 3 Ling Shi,1 Thomas K Welty,2 Rosanna F DeMarco,1 Teri Aronowitz1 1College of Nursing and Health Sciences, University of Massachusetts Boston, Boston, MA, USA; 2Cameroon Baptist Convention Health Services, Bamenda, Cameroon; 3Center for Women’s Reproductive Health, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL, USACorrespondence: Simon M Manga Tel +237 671863768Email smanga@cbchealthservices.orgPurpose: Treatment of cervical precancer is the primary aim in secondary prevention of cervical cancer. The purpose of this study was to examine factors associated with treatment uptake among women with acetic acid/Lugol’s iodine positive lesions identified by digital cervicography (DC) in a cervical cancer prevention program in Cameroon.Patients and Methods: We conducted a cross-sectional survey of medical records from 2013 to 2018 of 755 women in Cameroon who screened positive with acetic acid/Lugol’s iodine in 2013.Results: Of the 755 women, 422 (55.9%) had treatment/biopsy on the same day or followed up later, but only 344 (45.6%) received treatment/biopsy and 333 (44.1%) were lost to follow-up. Overall, 180 (52.3%) of the 344 women were treated/biopsied the same day they were screened, and 164 (47.7%) were treated/biopsied after the initial visit. Women aged 30– 49 and HIV-positive women were significantly more likely to have received treatment or returned for treatment than women less than 30 and HIV-negative women. Of the 266 women who followed up at a later date, the lesions of 78 (29.3%) women regressed spontaneously without treatment. Women with low-grade lesions, HIV-negative women and women who had follow-up more than a year after the initial exam were significantly more likely to have spontaneous regression with regression rates of 30.6%, 32.1% and 62.2%, respectively (p< 0.001). Age was not a significant determinant of spontaneous regression (p=0.149).Conclusion: Efforts to increase treatment uptake are needed in this population, including adherence to same day “See and treat” policies.Keywords: cervical precancer, treatment uptake, cameroon, cryotherapy, thermal ablation, loop electrosurgical excision procedure

Background and Objective: The ablative and excision treatment procedures are effective, accessible, and affordable in resource-constrained settings, but the rollout and posttreatment follow-up are not remarkable. The outcomes of treatment procedures among women treated for precancerous lesions of the cervix have not been adequately studied in Cameroon. This study assessed the outcome of ablative and excisional treatment procedures., Methods: This was a cross-sectional study that assessed the clinical outcome of 170 women treated for cervical precancers using ablative and excisional procedures in 2019 and 2020. Demographic and clinical data (treatment and posttreatment follow-up) were abstracted from the program registry. The data was analyzed to assess the clinical outcomes of cervical precancer treatment. The association between each independent variable and the dependent variable was examined in a simple logistic regression. All variables with p < 0.2 in the bivariate logistic regression model were subjected to a multivariable logistic model to get rid of cofounders and obtained adjustable odds ratios. The data was summarized using odds ratios, with p -value < 0.05 considered significant. All statistical analyses were performed using STATA version 17., Results: The cervical precancer treatment effectiveness of 93.55% was disaggregated into 94.37% and 88.23% for ablative and excisional procedures, respectively, with less severe adverse clinical effects. Despite the high awareness of women on the importance and timing of posttreatment follow-up, its uptake was 54.71%. Most of the women who got pregnant after the procedures delivered live and healthy babies. Women who were HIV positive were 89% (0.89 times) [aOR = 0.11, 95%CI (0.01 0.85), p = 0.034] less likely to have effective treatment for cervical precancer when compared to HIV-negative women. Those with low-grade lesions were eight times [aOR = 8.39, 95%CI (1.10 64.06), p = 0.04] more likely to have effective treatment for cervical precancer treatment compared to those with high-grade lesions., Conclusion and Global Health Implications: Ablative and excisional treatment procedures for cervical precancer were effective with limited adverse effects in Cameroon. Women living with HIV and those with large lesions experienced lower treatment effectiveness. Most of the women who got pregnant after the procedures delivered live and healthy babies. Posttreatment follow-up which is highly recommended because of recurrent/persistent lesions was barely above average., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Authors. Published by Global Health and Education Projects, Inc., USA.)

Introduction: cervical precancer screening with same day treatment facilitates maximization of benefits of secondary prevention of cervical cancer. This is particularly important for women living with human immunodeficiency virus (WLHIV) infection because of their exceptional risk for cervical cancer. The availability of HIV programmes in low- and middle-income countries (LMICs) provide unique opportunity for possible introduction "human papillomavirus (HPV) screening followed by visual inspection after application of acetic acid (VIA) with same day treatment of eligible patients". This study piloted this concept. Methods: in this prospective, cohort study, 98 WLHIV had HPV and VIA screening for cervical precancer lesions in a HIV clinic in Nigeria. Participants positive to HPV and/or VIA had biopsies from the visible lesions or quadrant of transformation zone. Participants positive to VIA and/or HPV16 or HPV18/45 had same-day thermal ablation treatment and the number of cases documented. The HPV, VIA and scenario of HPV followed by VIA results were compared with histologically confirmed cervical lesion grade 2 or worse statistically. Results: same day treatment was achieved in 95.0% of eligible cases. Statistically, sensitivity and specificity of VIA was 25.0% and 50.0% and HPV had 95.5% and 75.0%, respectively. In the HPV screening with VIA triage, sensitivity dropped to 45.5% but specificity improved to 100.0%. Conclusion: triaging HPV positive test with VIA for same-day treatment in cervical precancer screening among PLWHIV looks feasible. The improved specificity will reduce the overtreatment rate, loss to follow-up associated with repeat clinic visits and improve completion of continuum of care. [ABSTRACT FROM AUTHOR]

Simon Manga,1,2 Edith Kiyang,1 Rosanna F DeMarco2 1Women’s Health Program, Cameroon Baptist Convention Health Services, Bamenda, Cameroon; 2College of Nursing and Health Sciences, University of Massachusetts Boston, Boston, MA, USA Purpose: This pilot study explores the barriers to adherence to follow-up among women with cervical precancer in urban Cameroon. While follow-up of women with a positive screening of cervical precancer is the most important aspect of cervical cancer secondary prevention, women with cervical precancer do not adhere frequently to recommended follow-up schedule in Cameroon. The aim of the study was to explore and describe the barriers and facilitators to follow-up for cervical precancer among women infected and uninfected with HIV in Cameroon. Participants and methods: A qualitative research design was used to answer the research questions. Participants included eight HIV-infected and -uninfected women diagnosed with cervical precancer and 19 nurses. Data were collected by in-depth individual patient interviews and focus groups with nurses. An interview guide with open-ended questions, using the social ecological model as a framework, included questions that addressed the complexities of the lives of individuals and professionals within a relational context. The interviews were audio-taped and transcribed verbatim in English language. Thematic analysis of data was completed with no epistemological or theoretical perspective underpinning the analyses. Results: Four major themes emerged from the study. They were clinic, personal, and social barriers, and strategies to improve follow-up. Conclusion: The use of reminder phone calls and fee reduction, coupled with peer counseling and navigation of women who have been diagnosed with cervical precancer, could be effective ways of improving adherence to follow-up. Further research is needed to explore the same phenomenon among women in rural areas, especially those who were initially attended to in mobile clinics. Keywords: cervical precancer, follow-up, HIV-infected women, HIV-uninfected women

Background: Colposcopy was referred in cases with severe abnormalities in co-testing. Although p16/Ki67 dual staining reduced the referral rate, its sensitivity and specificity need to be enhanced. Methods: The expressions of p16, Ki-67, SMAD3, YAP1, RELA were evaluated in the colposcopy referral population. The inclusion criteria included 30– 60 years and diagnosed with HPV16/18-positive, other HR-HPV-positive with ASCUS, LSIL, AGC (atypical glandular cell) in co-testing. Colposcopies, endocervical curettages of cervical biopsies were also collected. Cases were excluded if there were no biopsies, if the interval between a cervical screening test and biopsies was more than 6 months, or if insufficient tissue was available as a formalin-fixed paraffin-embedded block. The pathology was independently reviewed by two pathologists. Discrepant interpretations were adjudicated by a third pathologist. Results: In total, 1194 of 1273 cases who were referred to colposcopy were evaluated in the present study. The sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 62.1% and 89.5%, respectively. p16+ combined with YAP1+ and/or RELA+ provided a sensitivity and specificity of 70.9% and 89.5%, respectively, while 72.8% and 86.4% were achieved by p16+ combined with YAP1+ and/or SMAD3+ and/or RELA+. In HPV16/18+ and LSIL subgroups, the sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 67.7% and 87.6%, respectively, for the former group and 58.6%, 88.8%, respectively, for the latter group. p16+, YAP1+/RELA+ showed a better performance for predicting CIN2+ with a better sensitivity and considerable specificity in the other HPV+ combined with ASCUS group than were achieved by p16+ combined with Ki-67+. RELA+ and the combination of p16 and RELA/YAP1 also provided the Max AUC area. Conclusion: Our study shows that RELA and the combination of p16 and RELA/YAP1 achieved better sensitivity and specificity for detecting morphologically CIN2+ lesions. [ABSTRACT FROM AUTHOR]

We report the ex vivo results of an in-house fabricated portable device based on polarized fluorescence measurements in the clinical environment. This device measures the polarized fluorescence and elastic scattering spectra with 405-nm laser and white light sources, respectively. The dominating fluorophore with 405-nm excitation is flavin adenine dinucleotide (FAD) with a fluorescence peak around 510 nm. The measured spectra are highly modulated by the interplay of scattering and absorption effects. Due to this, valuable information gets masked. To reduce these effects, intrinsic fluorescence was extracted by normalizing polarized fluorescence spectra with polarized elastic scattering spectra obtained. A number of fluorophores contribute to the fluorescence spectra and need to be decoupled to understand their roles in the progression of cancer. Nelder-Mead method has been utilized to fit the spectral profile with Gaussian to decouple the different bands of contributing fluorophores (FAD and porphyrin). The change in concentration of FAD during disease progression manifests in the change in ratio of total area to FWHM of its Gaussian profile. Receiver operating characteristic (ROC) curve analysis has been used to discriminate different grades of cervical precancer by using the ratio as input parameter. The sensitivity and specificity for discrimination of normal samples from CIN I (cervical intraepithelial neoplasia) are 75% and 54%, respectively. Further, the normal samples can be discriminated from CIN II samples with 100% and 82% sensitivity and specificity, respectively, and the CIN I from CIN II samples can also be discriminated with 100% sensitivity and 90% specificity, respectively. The results show that the change in the concentration of (FAD) can be used as a marker to discriminate the different grades of the cancer and biochemical changes at an early stage of the cancer can also be monitored with this technique. [ABSTRACT FROM AUTHOR]

In 2007, five Emerging Infections Program (EIP) sites were funded to determine the feasibility of establishing a population-based surveillance system for monitoring the effect of human papillomavirus (HPV) vaccine on pre-invasive cervical lesions. The project involved active population-based surveillance of cervical intraepithelial neoplasia grades 2 and 3 and adenocarcinoma in situ as well as associated HPV types in women >18 years of age residing in defined catchment areas; collecting relevant clinical information and detailed HPV vaccination histories for women 18–39 years of age; and estimating the annual rate of cervical cancer screening among the catchment area population. The first few years of the project provided key information, including data on HPV type distribution, before expected effect of vaccine introduction. The project’s success exemplifies the flexibility of EIP’s network to expand core activities to include emerging surveillance needs beyond acute infectious diseases. Project results contribute key information regarding the impact of HPV vaccination in the United States.

Context and Aim: Screening programs using conventional cytology conventional Pap smear (CPS) have successfully reduced cervical cancer, but newer tests like liquid-based cytology (LBC) and human papillomavirus testing might enhance screening. The main aim of the present study was to assess the diagnostic accuracy of LBC versus CPS using "split samples." Materials and Methods: This was a prospective study comprising of 1000 consecutive cervical "split samples" over a period of 1 year. Split sample was obtained using cervex-brush. CPS was prepared from the brush and the brush head was suspended in the LBC vial and processed by SurePath™ LBC. Results: There were 4.3% unsatisfactory (U/S) cases in CPS and 1.7% in LBC; the main cause is insufficient cells, and excess of blood in CPS. About 25/100 (2.5%) split samples had epithelial abnormalities both in CPS and LBC (1.2%-atypical squamous cells of undetermined significance; 0.4%-low grade squamous intraepithelial lesion; 0.2%-high grade squamous intraepithelial lesion; 0.5%-squamous cell carcinoma; 0.1%-atypical glandular cells favouring neoplasia; 0.2%-adenocarcinoma). Inflammatory organisms were almost equally identified in both techniques but were better seen in LBC samples. Conclusions: LBC technique leads to significant reduction of U/S rate. LBC samples offered better clarity, uniform spread of smears, less time for screening and better handling of hemorrhagic and inflammatory samples. LBC had equivalent sensitivity and specificity to CPS.

There is an unmet need for methods to help in the early detection of cervical precancer. Optical spec-troscopy-based techniques, such as Raman spectroscopy, have shown great potential for diagnosis of different cancers, including cervical cancer. However, relatively few studies have been carried out on liquid-based cytology (LBC) pap test specimens and confounding factors, such as blood contamination, have been identified. Previous work reported a method to remove blood contamination before Raman spectroscopy by pretreatment of the slides with hydrogen peroxide. The aim of the present study was to extend this work to excessively bloody samples to see if these could be rendered suitable for Raman spectroscopy. LBC ThinPrep specimens were treated by adding hydrogen peroxide directly to the vial before slide preparation. Good quality Raman spectra were recorded from negative and high grade (HG) cytology samples with no blood contamination and with heavy blood contamination. Good classification between negative and HG cytology could be achieved for samples with no blood contamination (sensitivity 92%, specificity 93%) and heavy blood contamination (sensitivity 89%, specificity 88%) with poorer classification when samples were combined (sensitivity 82%, specificity 87%). This study demonstrates for the first time the improved potential of Raman spectroscopy for analysis of ThinPrep specimens regardless of blood contamination. [ABSTRACT FROM AUTHOR]