Sexually transmitted infections and the HPV-related burden: evolution of Italian epidemiology and policy.

Sexually transmitted infections (STIs) are a major public health problem worldwide, with a high prevalence between the ages of 15 and 25 in most Western countries. High notification rates of chlamydia, gonorrhea, and syphilis are reported in the WHO European Region, with differences between countries. In Italy, the total number of STIs alerts increased by 18% from 2020 to 2021. HPV is the most common sexually transmitted infection; globally one in seven women is infected by this virus, and certain sexual behaviors are important risk factors for HPV-related cancers, particularly cervical cancer (CC), anogenital cancers and cancers of the head and neck. The burden of CC is relevant worldwide, in particular in Europe CC is the third leading cause of cancer-related deaths in women aged 15-44. This HPV-related tumor is preventable through a combined strategy of vaccination and screening for precursor lesions. In Italy, the coverage of organized screening varies from region to region and the average HPV vaccination rate is still far from the expected optimal threshold of 95% at the age of 12. To address the challenges of health promotion and HPV prevention, priority actions are needed such as: promoting education and information at every level, from schools to healthcare professionals. In Italy, education of adolescents on sexual and reproductive health, still remains critical, regionally inhomogeneous and much lower than in other European countries. Equitable measures need to be taken, and schools are an important place for health promotion activities.

HPV DNA Testing and Mobile Colposcopy for Cervical Precancer Screening in HIV Positive Women: A Comparison Between Two Settings in Ghana and Recommendation for Screening.

INTRODUCTION: Women living with HIV (WLHIV) have higher prevalence and persistence rates of high-risk human papillomavirus (hr-HPV) infection with a six-fold increased risk of cervical cancer. Thus, more frequent screening is recommended for WLHIV. OBJECTIVES: This retrospective descriptive cross-sectional study was conducted to investigate and compare the prevalence of hr-HPV infection and abnormal findings on mobile colposcopy in two cohorts of WLHIV following cervical screening in rural and urban settings in Ghana. METHODS: Through the mPharma 10 000 Women Initiative, WLHIV were screened via concurrent hr-HPV DNA testing (MA-6000; Sansure Biotech Inc., Hunan, China) and visual inspection (Enhanced Visual Assessment [EVA] mobile colposcope; MobileODT, Tel Aviv, Israel) by trained nurses. The women were screened while undergoing routine outpatient reviews at HIV clinics held at the Catholic Hospital, Battor (rural setting) and Tema General Hospital (urban setting), both in Ghana. RESULTS: Two-hundred and fifty-eight WLHIV were included in the analysis (rural, n = 132; urban, n = 126). The two groups were comparable in terms of age, time since HIV diagnosis, and duration of treatment for HIV. The hr-HPV prevalence rates were 53.7% (95% CI, 45.3-62.3) and 48.4% (95% CI, 39.7-57.1) among WLHIV screened in the rural vs urban settings (p-value = .388). Abnormal colposcopy findings were found in 8.5% (95% CI, 5.1-11.9) of the WLHIV, with no significant difference in detection rates between the two settings (p-value = .221). Three (13.6%) of 22 women who showed abnormal colposcopic findings underwent loop electrosurgical excision procedure (LEEP), leaving 19/22 women from both rural and urban areas with pending treatment/follow-up results, which demonstrates the difficulty faced in reaching early diagnosis and treatment, regardless of their area of residence. Histopathology following LEEP revealed CIN III in 2 WLHIV (urban setting, both hr-HPV negative) and CIN I in 1 woman in the rural setting (hr-HPV positive). CONCLUSIONS: There is a high prevalence of hr-HPV among WLHIV in both rural and urban settings in this study in Ghana. Concurrent HPV DNA testing with a visual inspection method (colposcopy/VIA) reduces loss to follow-up compared to performing HPV DNA testing as a standalone test and recalling hr-HPV positive women for follow up with a visual inspection method. Concurrent HPV DNA testing and a visual inspection method may also pick up precancerous cervical lesions that are hr-HPV negative and may be missed if HPV DNA testing is performed alone.

Cervical cancer screening among women with comorbidities: evidence from the 2022 Tanzania demographic and health survey.

BACKGROUND: The aim of this study is to examine cervical cancer screening (CCS) uptake among women living with hypertension and HIV in Tanzania. METHODS: We used the recently released 2022 Tanzania Demographic and Health Survey. The outcome variable assessed in the study was CCS, whereas chronic morbidities constituted the main explanatory variable. Data analysis was based on observations from 6,298 women aged 30-49 years. Multivariable logistic regression models were used to determine the association between hypertension and HIV status, and CCS uptake. The analyses were computed in STATA 18. RESULTS: Out of the 6,298 respondents, only 805 (12.8%) had undergone CCS with higher screening uptake among those living with either one of the disease (28.5%) than among those living with neither hypertension or HIV. The highest proportion was found among those who had ever been diagnosed with hypertension (24.1%) and among women with positive HIV test results (36.7%). There was a significantly higher likelihood of undergoing screening for cervical cancer among women living with at least one of the diseases [AOR = 2.4; 95% CI: 1.4-2.8], compared to those without these conditions. Women diagnosed with hypertension showed increased likelihood of undergoing CCS [AOR = 1.4; 95%CI: 1.1-1.7]. Similarly, women with a positive HIV test result demonstrated higher odds of screening uptake [AOR = 5.2; 95%CI: 4.0-6.7]. CONCLUSION: The study found a positive association between comorbidities and CCS uptake in Tanzanian women. Our findings emphasize the critical importance of ensuring accessibility and adherence to essential screenings for individuals with chronic morbid conditions. Future efforts should focus on strengthening existing integrated services and identifying potential barriers to accessing CCS within these healthcare settings to optimize cervical cancer prevention efforts for individuals with chronic morbidities.

Knowledge about cervical cancer in young Portuguese women: a cross-sectional study.

Introduction: Health literacy is crucial to adherence to medical interventions in therapeutics, prevention, and diagnosis. The basis for literacy is knowledge. To accomplish the goals for the elimination of cervical cancer, one of the most prevalent and preventable cancers, we must understand the determinants of non-adherence and address them specifically to ensure patients' active participation. Aim: To determine women's knowledge regarding the manifestations of cervical cancer and its prevention. Materials and methods: We conducted a cross-sectional study in an urban population from northern Portugal. Women aged 18 to 30 years were randomly assigned to answer the Cervical Cancer Awareness Measure questionnaire, including questions of knowledge about the causes and symptoms of cervical cancer, prospecting for individual and social-related determinants. Results: The total number of participants was 270, with a mean age of 24.7 years. Knowledge about symptoms scored 5.4 ± 2.6, with a maximum of 12 points, and knowledge about the causes scored 5.7 ± 1.9, with a maximum of 11 points. The correlation between both was 0.334. High education, high socio-economic status, self-perception of one's capacity to recognize symptoms, and knowledge about the HPV vaccine were associated with better knowledge. Discussion: Portuguese women present low knowledge about cervical cancer, potentially affecting their health through exposure to risk situations and non-adherence to routine screening.

For due or overdue cervical cancer screening, direct or opt-in mailing of HPV self-sampling increased screening at 6 mo vs. education.

SOURCE CITATION: Winer RL, Lin J, Anderson ML, et al. Strategies to increase cervical cancer screening with mailed human papillomavirus self-sampling kits: a randomized clinical trial. JAMA. 2023;330:1971-1981. 38015219.

Development and validation of prognostic nomographs for patients with cervical cancer: SEER-based Asian population study.

To develop and validate a nomograph to predict the long-term survival probability of cervical cancer (CC) patients in Asia, Surveillance, Epidemiology, and End Results (SEER) were used to collect information about CC patients in Asia. The patient data were randomly sampled and divided into a training group and a validation group by 7:3. Least absolute shrinkage and selection operator (LASSO) regression was used to screen key indicators, and multivariate Cox regression model was used to establish a prognostic risk prediction model for CC patients. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were adopted to comprehensively evaluate the nomogram model. LASSO regression and multivariate Cox proportional hazards model analysis showed that age, American Joint Committee on Cancer (AJCC) Stage, AJCC T, tumor size, and surgery were independent risk factors for prognosis. The ROC curve results proved that the area under curve (AUC) values of the training group in 3 and 5 years were 0.837 and 0.818, The AUC values of the validation group in 3 and 5 years were 0.796 and 0.783. DCA showed that the 3- and 5-year overall survival (OS) nomograms had good clinical potential value. The nomogram model developed in this study can effectively predict the prognosis of Asian patients with CC, and the risk stratification system based on this nomogram prediction model has some clinical value for discriminating high-risk patients.

Analysis of related factors for pathological upgrading of cervical biopsy from CIN3 to cancer after conical resection.

BACKGROUND: To investigate related factors for postoperative pathological upgrading of cervical biopsy to cervical cancer (CC) in patients with cervical intraepithelial neoplasia (CIN)3 after conical resection. METHODS: This retrospective study collected data from patients diagnosed with CIN3 by cervical biopsies at the author's Hospital between January 2012 and December 2022. The primary outcome was the pathological results of patients after conical resection. The pathological findings were categorized into the pathological upgrading group if postoperative pathology indicated CC, while those with normal, inflammatory, or cervical precancerous lesions were classified into the pathological non-upgrading group. The factors associated with upgrading were identified using multivariable logistic regression analysis. RESULTS: Among 511 patients, there were 125 patients in the pathological upgrading group (24.46%). The patients in the upgrading group were younger (47.68 ± 9.46 vs. 52.11 ± 7.02, P < 0.001), showed a lower proportion of menopausal women (38.40% vs. 53.02%, P = 0.0111), a lower proportion of HSIL (40.00% vs. 57.77%, P = 0.001), a higher rate of HPV-16/18 positive (25.60% vs. 17.36%, P = 0.011), a higher rate of contact bleeding (54.40% vs. 21.50%, P < 0.001), lower HDL levels (1.31 ± 0.29 vs. 1.37 ± 0.34 mmol/L, P = 0.002), higher neutrophil counts (median, 3.50 vs. 3.10 × 109/L, P = 0.001), higher red blood cell counts (4.01 ± 0.43 vs. 3.97 ± 0.47 × 1012/L, P = 0.002), higher platelet counts (204.84 ± 61.24 vs. 187.06 ± 73.66 × 109/L, P = 0.012), and a smaller platelet volume (median, 11.50 vs. 11.90 fL, P = 0.002).The multivariable logistic regression analysis showed that age (OR = 0.90, 95% CI: 0.86-0.94, P < 0.001), menopausal (OR = 2.68, 95% CI: 1.38-5.22, P = 0.004), contact bleeding (OR = 4.80, 95% CI: 2.91-7.91, P < 0.001), and mean platelet volume (OR = 0.83, 95% CI: 0.69-0.99, P = 0.038) were independently associated with pathological upgrading from CIN3 to CC after conical resection. CONCLUSION: Age, menopausal, contact bleeding, and mean platelet volume are risk factors of pathological upgrading from CIN3 to CC after conical resection, which could help identify high risk and susceptible patients of pathological upgrading to CC.

Willingness of healthcare providers to perform population-based cancer screening: a cross-sectional study in primary healthcare institutions in Tianjin, China.

OBJECTIVE: To evaluate the willingness of healthcare providers to perform population-based screening in primary healthcare institutions in China. METHODS: Healthcare providers of 262 primary healthcare institutions in Tianjin were invited to fill out a questionnaire consisting of demographic characteristics, workload, and knowledge of, attitude towards and willingness to perform breast, cervical and colorectal cancer screening. Willingness to screen was the primary outcome. Multilevel logistic regression models were conducted to analyse the determinants of healthcare providers' willingness to screen. ORs and 95% CIs were estimated. RESULTS: A total of 554 healthcare providers from 244 institutions answered the questionnaire. 67.2%, 72.1% and 74.3% were willing to perform breast, cervical and colorectal cancer screening, respectively. A negative attitude towards screening was associated with a low willingness for cervical (OR=0.27; 95% CI 0.08, 0.94) and colorectal (OR=0.08; 95% CI 0.02, 0.30) cancer screening, while this was not statistically significant for breast cancer screening (OR=0.30; 95% CI 0.08, 1.12). For breast, cervical and colorectal cancer screening, 70.1%, 63.8% and 59.0% of healthcare providers reported a shortage of staff dedicated to screening. A perceived reasonable manpower allocation was a determinant of increased willingness to perform breast (OR=2.86; 95% CI 1.03, 7.88) and colorectal (OR=2.70; 95% CI 1.22, 5.99) cancer screening. However, this was not significant for cervical cancer screening (OR=1.76; 95% CI 0.74, 4.18). CONCLUSIONS: In China, healthcare providers with a positive attitude towards screening have a stronger willingness to contribute to cancer screening, and therefore healthcare providers' attitude, recognition of the importance of screening and acceptable workload should be optimised to improve the uptake of cancer screening.

Early age at menarche and history of sexually transmitted infections significantly predict cervical cancer screening uptake among women aged 25-49 years: evidence from the 2021 Côte d'Ivoire demographic and health survey.

INTRODUCTION: Cervical cancer is the second dominant type of cancer among Ivorian women with an estimated age-standardised incidence and mortality rate of 31.2 cases and 22.8 deaths per 100,000 women in 2020, respectively. The Ivorian government through its Ministry of Health implemented the National Cancer Control Programme (NCCP) in 2003 with the aim of improving the prevention, early detection and treatment of cancers in Côte d'Ivoire. Yet, there is a low uptake of CCS (1.2%). Thus, making CCS uptake an important public health concern in the country. Understanding of the extent to which reproductive factors predict CCS uptake is limited in literature. This study aimed to investigate reproductive factors as a predictor of women's uptake of CCS in Côte d'Ivoire. METHODS: Data from the 2021 Côte d'Ivoire Demographic and Health Survey. A sample of 9,078 women aged 25-49 years were analyzed. The outcome variable was CCS uptake while other variables considered included age at menarche, history of STI, sexual debut, parity, age, educational level, wealth index, health insurance, place of residence, and media exposure. A multivariable logistic regression model was fitted to examine the association between the outcome of interest and predictors at 95% confidence interval. RESULTS: Approximately, 7.52% of women aged 25-49 years had ever undergone testing for cervical cancer by a healthcare provider. Early menarche was associated with lower odds of CCS uptake [AOR = 0.78; CI = 0.65-0.95]. Compared to those who had no STI, women with a history of STI were more likely to screen for cervical cancer [AOR = 2.63; CI = 2.02-3.42]. Increasing age, higher educational attainment, having health insurance, and being exposed to media were significantly associated with CCS uptake. CONCLUSION: In Cote d'Ivoire, age at menarche and STI history constitute reproductive factors that were significantly associated with women's uptake of CCS. It is imperative for public policy to focus on increasing CCS in these higher-risk women (i.e., women who experienced early menarche, women with early sexual debut and higher parity) through increased sensitization on cervical cancer risk factors.

Clinical characteristics, HPV involvement, and demographic risk factors in women with cervical intraepithelial neoplasia complicated by vaginal intraepithelial neoplasia.

PURPOSE: This study aimed to explore the clinical characteristics and risk factors associated with cervical intraepithelial neoplasia (CIN) when coexisting with vaginal intraepithelial neoplasia (VAIN). METHODS: We analyzed the clinical data of 212 patients diagnosed with CIN, including 50 patients with concurrent VAIN. The groups were compared to identify distinct clinical features and independent risk factors for the co-occurrence of CIN and VAIN, using logistic regression analysis. RESULTS: Patients with both CIN and VAIN had a median age of 57, significantly older than the 41-year median age of patients with CIN only (P < 0.05). A higher prevalence of HPV infection (98.0%) was observed in the CIN and VAIN group, with a notable rate of multiple HPV infections (67.3%) compared to the CIN-only group (P < 0.05). Educational levels were significantly lower in the combined CIN and VAIN group (P < 0.05). HPV16, 33, and 52 were identified as significant types for single and multiple infections. Multivariate analysis confirmed age as an independent risk factor for CIN with VAIN (P < 0.05). VAIN3 patients were more likely to exhibit HSIL and ASC-H, whereas VAIN1 cases tended to correspond with ASCUS and LSIL diagnoses. CONCLUSION: The co-occurrence of CIN and VAIN is significantly influenced by patient age and educational level. The findings advocate for more diligent vaginal examination during colposcopy in older patients, particularly those with multiple HPV infections and cytological abnormalities, to enhance the early detection of vaginal lesions and prevent missed diagnoses and treatments. Additionally, the high prevalence of HPV infection, especially with certain types, underscores the importance of HPV monitoring in this patient population.

[Application of optical coherence tomography in the evaluation of cervical lesions: a multicenter study].

Objective: To explore the value of optical coherence tomography (OCT) imaging system in evaluating cervical lesions in vivo. Methods: A total of 1 214 patients with cervical lesions were collected from January 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University, Maternal and Chlid Heaith Hospital of Gushi County, Xinyang City, Henan Province, and Maternal and Chlid Heaith Hospital of Sui County, Shangqiu City, Henan Province. The age of the patients was (38.9±10.5) years (range: 16-77 years). All patients underwent in vivo cervical OCT examination and cervical biopsy pathology examination, and summarized the OCT image features of in vivo cervical lesions. Using the pathological diagnosis as the "gold standard", the accuracy, specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of OCT image interpretation results were evaluated, as well as the consistency of OCT image diagnosis and pathological diagnosis. At the same time, the in vivo cervical OCT imaging system, as a newly developed screening tool, was compared with the traditional combined screening of human papillomavirus (HPV) and Thinprep cytologic test (TCT), to assess the screening effect. Results: By comparing the OCT images of the cervix in vivo with the corresponding HE images, the OCT image characteristics of the normal cervix and various types of cervical lesions in vivo were summarized. The accuracy, sensitivity, specificity, PPV and NPV of OCT image in the diagnosis of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL+) were 93.4%, 88.5%, 95.0%, 85.0% and 96.2%, respectively. The accuracy, sensitivity, specificity, PPV and NPV of OCT for low-grade squamous intraepithelial lesion (LSIL) were 84.7%, 61.7%, 96.3%, 89.3% and 83.2%, respectively. The consistency between OCT image diagnosis and pathological diagnosis was strong (Kappa value was 0.701).The accuracy, sensitivity and specificity of OCT screening, HPV and TCT combined screening were 83.7% vs 64.9% (χ²=128.82, P<0.001), 77.8% vs 64.5% (χ²=39.01, P<0.001), 91.8% vs 65.4% (χ²=98.12, P<0.001), respectively. The differences were statistically significant. Conclusions: OCT imaging system has high sensitivity and specificity in the evaluation of cervical lesions in vivo, and has the characteristics of non-invasive, real-time and high efficiency. OCT examination is expected to become an effective method for the diagnosis of cervical lesions and cervical cancer screening.

Impact of virtual education based on health belief model on cervical cancer screening behavior in middle-aged women: A quasi-experimental study.

BACKGROUND: Cervical cancer is one of the most common cancers in women worldwide and a cause of high mortality among people. Pap smear screening is an appropriate method to prevent cervical cancer and reduce its mortality. AIM: This study aimed to determine the effect of web-based education based on the Health Belief Model (HBM) on cervical cancer screening behavior in middle-aged women. METHODS AND RESULTS: This study is a quasi-experimental interventional research that was conducted on 240 middle-aged women aged 40-59 years in Isfahan, Iran, in 2022. An online educational intervention based on the constructs of the Health Belief Model was conducted for the intervention group using the Triple-B platform. The information on the intervention and control groups was collected before, immediately after the intervention, and 2 months later using a valid questionnaire. The gathered Data was analyzed using ANOVA and LSD post-hoc, independent samples t test, chi-square, and MANCOVA statistical tests in SPSS 26 software. After the intervention, the mean scores of knowledge, perceived susceptibility, perceived severity, perceived benefits, self-efficacy, and internal cues to action in the intervention group increased and the mean score of perceived barriers decreased (p < .001). The mean score of the external cues to action did not show a significant difference between the intervention and control groups before, immediately, and 2 months after the intervention. Two months after the intervention, 32 women (26.2%) in the intervention group and two women (1.7%) in the control group performed the Pap smear test. CONCLUSION: Web-based educational intervention based on HBM using different strategies such as question and answer, presentation of infographics, lectures, brainstorming, showing videos and numerous educational images can be an effective way for increasing knowledge and cognitive variables of women and doing Pap smear test.

Psychometric properties of a modified health belief model for cervical cancer and visual inspection with acetic acid among healthcare professionals in Ethiopia.

PURPOSE: Evidence supports that the Health Belief Model (HBM) can explain and predicts certain health behaviors, including participation in cervical cancer (CC) screening. The purpose of this study was to evaluate the psychometric properties of a modified HBM for CC and visual inspection with acetic acid (VIA) in female healthcare professionals in Addis Ababa, Ethiopia, 2020. METHODS: Psychometric properties related to CC and VIA were tested using 42-item modified HBM self-administered questionnaire and a cross-sectional study design with simple random sampling. Kaiser-Meyer-Olkin and Bartlett's sphericity test indicated that data sampling adequacy for exploratory factor analysis was 0.792 (χ2 = 3189.95, df = 351, p < .001). Items with cross-loading and factor loadings ≥ 0.5 were retained. Confirmatory factor analysis (CFA) was conducted to determine model fit. RESULTS: The final analysis included 194 women, (mean age 30±4.34). Twelve items with ≤ 0.5 were removed and 30 retained items loaded into 6 factors; (benefits of VIA, perceived seriousness of CC, barrier (fear of negative outcome), self-efficacy, susceptibility to CC, and barriers (health system delivery)) explained 65% of the total variance. Cronbach's alpha for the total instrument was 0.8 and reliability for the 6 subscales was 0.76-0.92. Composite reliability and average variance extracted indicated good internal consistency and convergent validity. CFA identified 6 additional items to be removed with high residual covariance. The final 24 items of the modified HBM had an acceptable model fit (goodness-of-fit index (GFI) = 0.861, adjusted GFI = 0.823, comparative fit index = 0.937, root mean square error of approximation = 0.059). CONCLUSION: The modified HBM for CC and VIA with 24 items had adequate psychometric properties and may be used by Ethiopian healthcare professionals for research or clinical purposes. To support external validity the updated 24 items tool is suggested for application in further study in different populations in Ethiopia.

Baseline knowledge on risk factors, symptoms and intended behavior of women and men towards screening and treatment of cervical cancer in rural Uganda: a cross-sectional study.

BACKGROUND: Knowledge of risk factors and symptoms of cervical cancer has been found to promote uptake of screening of cervical cancer. Most interventions targeted women without much involvement of men (husbands/decision makers) who are often decision makers in many low- and middle-income countries. This study aimed at assessing baseline knowledge and intended behavior of both women and men to enable design specific targeted messages to increase uptake of cervical cancer screening and promote early detection of women with symptoms. METHODS: This cross-sectional study was conducted in two districts in Western Uganda using the modified African Women Awareness of CANcer (AWACAN) questionnaire. Women aged 30-49 years and their husbands/decision makers were interviewed. Knowledge on risk factors and symptoms, intended behavior and barriers towards participation in cervical cancer screening and treatment were assessed. Descriptive and logistic regression analyses were done to establish the association between knowledge levels and other factors comparing women to men. RESULTS: A total of 724 women and 692 men were enrolled. Of these, 71.0% women and 67.2% men had ever heard of cervical cancer and 8.8% women had ever been screened. Knowledge of risk factors and symptoms of cervical cancer was high and similar for both women and men. Lack of decision making by women was associated with low knowledge of risk factors (X2 = 14.542; p = 0.01), low education (X2 = 36.05, p < 0.01) and older age (X2 = 17.33, p < 0.01). Men had better help seeking behavior than women (X2 = 64.96, p < 0.01, OR = 0.39, 95% CI: 0.31-0.50) and were more confident and skilled in recognising a sign or symptom of cervical cancer (X2 = 27.28, p < 0.01, OR = 0.52, CI (0.40-0.67). CONCLUSION: The baseline knowledge for cervical cancer was high in majority of participants and similar in both women and men. Their intended behavior towards screening was also positive but screening uptake was very low. This study suggests developing messages on multiple interventions to promote screening behavior in addition to education, consisting of male involvement, women empowerment and making services available, accessible and women friendly.

Aggressive precursor B cell ALL of cervix with obstructive uropathy.

Involvement of the cervix with acute lymphoblastic leukaemia (ALL) is extremely rare. In this case report, we discuss an unmarried woman in her early 20s, who presented in the emergency with lower abdominal pain and irregular vaginal bleeding for 1 month. Clinical examination and imaging revealed a large cervical mass probably neoplastic with obstructive uropathy. On evaluation, she was diagnosed incidentally with CALLA-positive precursor B cell ALL in peripheral blood flow cytometry. Involvement of B cell ALL in cervical mass was confirmed by histopathological examination of cervical biopsy and immunohistochemistry markers. Her history was not suggestive of signs and symptoms pertaining to leukaemia. Literature is sparse with only a few cases reporting cervical leukaemic infiltration. The present case report is a rarest case where the primary/initial presentation of precursor B cell ALL was seen with cervical involvement and obstructive uropathy mimicking characteristics of advanced cervical malignancy.

Strategies for primary HPV test-based cervical cancer screening programme in resource-limited settings in India: Results from a quasi-experimental pragmatic implementation trial.

BACKGROUND: In order for low and middle income countries (LMIC) to transition to Human Papilloma Virus (HPV) test based cervical cancer screening, a greater understanding of how to implement these evidence based interventions (EBI) among vulnerable populations is needed. This paper documents outcomes of an implementation research on HPV screening among women from tribal, rural, urban slum settings in India. METHODS: A mixed-method, pragmatic, quasi-experimental trial design was used. HPV screening on self-collected cervical samples was offered to women aged 30-60 years. Implementation strategies were 1) Assessment of contextual factors using both qualitative and quantitative methods like key informant interviews (KII), focus group discussions (FGDs), pre-post population sample surveys, capacity assessment of participating departments 2) enhancing provider capacity through training workshops, access to HPV testing facility, colposcopy, thermal ablation/cryotherapy at the primary health care centers 3) community engagement, counselling for self-sampling and triage process by frontline health care workers (HCWs). Outcomes were assessed using the RE-AIM (Reach, Effectiveness, adoption, implementation, maintenance) framework. RESULTS: Screening rate in 8 months' of study was 31.0%, 26.7%, 32.9%, prevalence of oncogenic HPV was 12.1%, 3.1%, 5.5%, compliance to triage was 53.6%, 45.5%, 84.6% in tribal, urban slum, rural sites respectively. Pre-cancer among triage compliant HPV positive women was 13.6% in tribal, 4% in rural and 0% among urban slum women. Unique challenges faced in the tribal setting led to programme adaptations like increasing honoraria of community health workers for late-evening work and recalling HPV positive women for colposcopy by nurses, thermal ablation by gynaecologist at the outreach camp site. CONCLUSIONS: Self-collection of samples combined with HCW led community engagement activities, flexible triage processes and strengthening of health system showed an acceptable screening rate and better compliance to triage, highlighting the importance of identifying the barriers and developing strategies suitable for the setting. TRIAL REGISTRATION: CTRI/2021/09/036130.

Endometrial Cancer Detection by DNA Methylation Analysis in Cervical Papanicolaou Brush Samples.

Background: Endometrial cancer (EC) is the leading gynecological cancer worldwide, yet current EC screening approaches are not satisfying. The purpose of this retrospective study was to evaluate the feasibility and capability of DNA methylation analysis in cervical Papanicolaou (Pap) brush samples for EC detection. Methods: We used quantitative methylation-sensitive PCR (qMS-PCR) to determine the methylation status of candidate genes in EC tissue samples, as well as cervical Pap brushes. The ability of RASSF1A and HIST1H4F to serve as diagnostic markers for EC was then examined in cervical Pap brush samples from women with endometrial lesions of varying degrees of severity. Results: Methylated RASSF1A and HIST1H4F were found in EC tissues. Further, methylation of the two genes was also observed in cervical Pap smear samples from EC patients. Methylation levels of RASSF1A and HIST1H4F increased as endometrial lesions progressed, and cervical Pap brush samples from women affected by EC exhibited significantly higher levels of methylated RASSF1A and HIST1H4F compared to noncancerous controls (P < .001). Receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses revealed RASSF1A and HIST1H4F methylation with a combined AUC of 0.938 and 0.951 for EC/pre-EC detection in cervical Pap brush samples, respectively. Conclusion: These findings demonstrate that DNA methylation analysis in cervical Pap brush samples may be helpful for EC detection, broadening the scope of the commonly used cytological screening. Our proof-of-concept study provides new insights into the field of clinical EC diagnosis.

Discovery and technical validation of high-performance methylated DNA markers for the detection of cervical lesions at risk of malignant progression in low- and middle-income countries.

BACKGROUND: Cervical cancer remains a leading cause of death, particularly in developing countries. WHO screening guidelines recommend human papilloma virus (HPV) detection as a means to identify women at risk of developing cervical cancer. While HPV testing identifies those at risk, it does not specifically distinguish individuals with neoplasia. We investigated whether a quantitative molecular test that measures methylated DNA markers could identify high-risk lesions in the cervix with accuracy. RESULTS: Marker discovery was performed in TCGA-CESC Infinium Methylation 450 K Array database and verified in three other public datasets. The panel was technically validated using Quantitative Multiplex-Methylation-Specific PCR in tissue sections (N = 252) and cervical smears (N = 244) from the USA, South Africa, and Vietnam. The gene panel consisted of FMN2, EDNRB, ZNF671, TBXT, and MOS. Cervical tissue samples from all three countries showed highly significant differential methylation in squamous cell carcinoma (SCC) with a sensitivity of 100% [95% CI 74.12-100.00], and specificity of 91% [95% CI 62.26-99.53] to 96% [95% CI 79.01-99.78], and receiver operating characteristic area under the curve (ROC AUC) = 1.000 [95% CI 1.00-1.00] compared to benign cervical tissue, and cervical intraepithelial neoplasia 2/3 with sensitivity of 55% [95% CI 37.77-70.84] to 89% [95% CI 67.20-98.03], specificity of 93% [95% CI 84.07-97.38] to 96% [95% CI 79.01-99.78], and a ROC AUC ranging from 0.793 [95% CI 0.68-0.89] to 0.99 [95% CI 0.97-1.00] compared to CIN1. In cervical smears, the marker panel detected SCC with a sensitivity of 87% [95% CI 77.45-92.69], specificity 95% [95% CI 88.64-98.18], and ROC AUC = 0.925 [95% CI 0.878-0.974] compared to normal, and high-grade squamous intraepithelial lesion (HSIL) at a sensitivity of 70% (95% CI 58.11-80.44), specificity of 94% (95% CI 88.30-97.40), and ROC AUC = 0.884 (95% CI 0.822-0.945) compared to low-grade intraepithelial lesion (LSIL)/normal in an analysis of pooled data from the three countries. Similar to HPV-positive, HPV-negative cervical carcinomas were frequently hypermethylated for these markers. CONCLUSIONS: This 5-marker panel detected SCC and HSIL in cervical smears with a high level of sensitivity and specificity. Molecular tests with the ability to rapidly detect high-risk HSIL will lead to timely treatment for those in need and prevent unnecessary procedures in women with low-risk lesions throughout the world. Validation of these markers in prospectively collected cervical smear cells followed by the development of a hypermethylated marker-based cervical cancer detection test is warranted.