Cervical Cancer Screening Services in Nepal: A Descriptive Crosssectional Study.

INTRODUCTION: Cervical cancer, the most prevalent cancer among women, is also the primary cause of cancer-related deaths in reproductive age women in Nepal. The study aims to assess the situation of cervical cancer screening services in Nepal. METHODS: This cross-sectional study used quantitative methods to understand the situation of cervical cancer screening in 572 health facilities of Nepal. The research was conducted to assess screening facilities, the allocation of separate screening rooms, the availability of screening services on a routine basis throughout the week, screening facilities that are free of charge, human resources, and the availability of treatment. It was conducted in October to December 2022. RESULTS: The research was carried out among 572 healthcare facilities, out of which 134 (23.42%) had provision for cervical cancer screening services. Ethical approval was obtained from the Nepal Health Research Council (NHRC) under reference number 397/2022 P. Amongst those 134, 72 (53.73%) healthcare facilities had assigned separate rooms for screening intentions. One hundred and two (76.12%) healthcare facilities provided regular screening services throughout the week, while 112 (83.58 %) had free-of-charge  screening services. Concerning trained personnel, 121 (90.30%) health facilities had personnel trained in visual inspection with Acetic acid, 9 (6.72%) had personnel trained in use of colposcopy, and 5 (3.73%) had personnel trained in use of Loop Electrosurgical Excision Procedure (LEEP). Lastly, 31 (23.13%) healthcare facilities offered treatment choices for cervical cancer. CONCLUSIONS: Most of the health care facilities did not have provision of cervical screening. Amongst those who had the provision, personnel trained in loop electrosurgical excision procedure colposcopy.

Prevalence and Description of High-Grade Intraepithelial Lesions of Cervical Mucosa Cells in a Screening Programme for Cervical Cancer in Isère, France.

OBJECTIVE: This study aims to analyse high-grade intraepithelial lesions (LIEHG) observed in a screening programme from 2010 to 2018 to more accurately describe them and formulate recommendations for best practices in the context of screening evolution following the introduction of an HPV test in primary cervical cancer screening in 2020. METHODS: This study included 305,940 asymptomatic women aged 25-65 years. The eligible population was invited to undergo a screening cervico-uterine-smear every 3 years. If this smear was normal, the woman received a new invitation. In the case of a positive screen, the patient underwent further diagnostic procedures, such as colposcopy and biopsy to confirm the diagnosis. Only those diagnosed with LIEHG and above proceeded to treatment. The diagnoses associated with LIEHG were those related to the WHO Classification of tumours of the uterine cervix. RESULTS: Positive smears led to the diagnosis of 3230 LIEHG. The prevalence of LIEHG in the screened population was 0.4%. The LIEHG distribution varied significantly according to the age of the women. The probability of diagnosing LIEHG in young women was 12.2% at 25-29 years. This probability decreased by half after 50 years. We observed that the type of smear was significantly associated with LIEHG detection. The positive predictive value for diagnosing LIEHG was 70.3% for high-grade squamous intraepithelial lesion (HSIL) smears and 35.1% for atypical squamous cells cannot exclude HSIL (ASC-H) smears. CONCLUSION: In the study population, the prevalence of LIEHG was high in women under 35 years. Low-grade smears were correlated with the risk of LIEHG and should prompt screening facilities to allocate resources to ensure active follow-up of LSIL and ASC-US smears. Adherence to cytological screening recommendations was associated with a reduced risk of LIEHG in multivariate analysis.

[Clinical effect of secondary LEEP combined with transcervical resection of endocervical tissue for cervical precancerous lesions with positive internal margin after the first LEEP].

Objective: To preliminarily investigate the clinical outcomes of secondary loop electrosurgical excision procedure (LEEP) combined with transcervical resection of endocervical tissue (i.e., second combined surgeries) in patients with positive endocervical margins following the initial LEEP for high-grade squamous intraepithelial lesion (HSIL) or adenocarcinoma in situ (AIS) of the cervix. Methods: Patients who underwent second combined surgeries due to positive endocervical margins after the initial LEEP for cervical HSIL or AIS at Obstetrics and Gynecology Hospital, Fudan University between August 2015 and September 2023 were included. Postoperative cytological examinations, high-risk human papillomavirus (HR-HPV) testing, colposcopic biopsy results, and cervical canal length were followed up to evaluate the clinical efficacy of second combined surgeries. Results: (1) General clinical data: a total of 67 patients were enrolled, including 34 with cervical HSIL (HSIL group) and 33 with AIS (AIS group). In the HSIL group before the time of initial LEEP, the mean age was (41.3±5.3) years, with all patients positive for HR-HPV preoperatively. Preoperative cytology results revealed ≤low-grade squamous intraepithelial lesion (LSIL) in 13 cases and ≥HSIL in 21 cases. The preoperative cervical canal length was (3.71±0.17) cm. Patients in the AIS group before their the first LEEP were at an average age of (39.1±8.7) years old, with preoperative HR-HPV positive. Among them, 16 cases showed preoperative cytological results of ≤LSIL, while 17 cases showed ≥HSIL. The preoperative cervical canal length was (3.64±0.21) cm. (2) Pathological findings and postoperative follow-up of the HSIL group following second combined surgeries:in the HSIL group, the residual rate of HSIL in the endocervical canal tissue (ECT) was 24% (8/34). Out of the 34 HSIL patients, 10 cases (29%, 10/34) remained with positive endocervical margins post-second combined surgeries. Among these 10 patients, 5 cases (5/10) had no lesion detected in ECT, while the remaining 5 cases (5/10) exhibited HSIL in their ECT. Conversely, 24 patients (71%, 24/34) had negative endocervical margins after second combined surgeries. Of these 24 patients, 3 cases (12%, 3/24) were found to have HSIL in ECT, and 21 cases (88%, 21/24) had no lesion in ECT. During follow-ups conducted at 6 and 12 months post-second combined surgeries, the clearance rates of HR-HPV were 91% (31/34) and 100% (34/34), respectively. Notably, among the 29 patients (85%, 29/34) who were followed up for a period of 2 years or longer, all cases maintained a consistently negative HR-HPV status, highlighting the effectiveness of second combined surgeries in achieving long-term HR-HPV clearance (100%, 29/29). (3) Pathological findings and postoperative follow-up of the AIS group following second combined surgeries: the residual rate of AIS in the ECT following second combined surgeries among AIS patients was 15% (5/33). Out of the 33 AIS patients, 11 cases (33%, 11/33) had positive endocervical margins post-operation, among whom AIS was detected in the ECT of 2 cases (2/11), while 1 case (1/11) was diagnosed with adenocarcinoma in the cervical canal tissue (subsequently underwent radical surgery and was excluded from this study). In contrast, 22 patients (67%, 22/33) had negative endocervical margins post-operation, with AIS found in the ECT of 2 cases (9%, 2/22) and no lesions detected in the remaining 20 cases (91%, 20/22). Follow-up evaluations conducted at 6 and 12 months postoperatively revealed HR-HPV clearance rates of 91% (29/32) and 97% (31/32), respectively. All 32 (100%, 32/32) AIS patients were followed up for a duration of ≥2 years post-second combined surgeries, during which HR-HPV remained consistently negative. (4) Complications and cervical length following second combined surgeries: neither the HSIL group nor the AIS group experienced significant complications such as hemorrhage, infection or cervical canal adhesion. At the 6-month follow-up, the cervical length of both HSIL and AIS patients exceeded 3 cm. By the 12-month follow-up, the cervical length had recovered to 96.5% and 97.5% when compared to the original length, respectively, for the HSIL and AIS groups. Conclusions: For patients with HSIL or AIS who exhibit positive endocervical margins following the initial LEEP procedure, undergoing second combined surgeries presents as an optimal choice. This surgical intervention guarantees thorough excision of the lesion, and subsequent colposcopic follow-up evaluations consistently demonstrate an absence of residual disease or recurrence. Moreover, it augments the rate of sustained HR-HPV negativity, thereby contributing to more favorable clinical outcomes.

Detecting the impact of diagnostic procedures in Pap-positive women on anxiety using artificial neural networks.

INTRODUCTION: Women who receive a result of an abnormal Papanicolaou (Pap) smear can fail to participate in follow up procedures, and this is often due to anxiety. This study aimed to apply artificial neural networks (ANN) in prediction of anxiety in women with an abnormal Pap smear test, prior to and following diagnostic procedures. METHODS: One hundred-seventy two women who received an abnormal Pap screening result took part in this study, completing a questionnaire about socio-demographic characteristics and Hospital Anxiety and Depression Scale (HADS), right before and two to four weeks after diagnostics (i.e. colposcopy/biopsy/endocervical curettage). A feedforward back-propagation multilayer perceptron model was applied in analysis. RESULTS: Prior to diagnostic procedures 50.0% of women experienced anxiety, while after diagnostics anxiety was present in 61.6% of women. The correlation-based feature selection showed that anxiety prior to diagnostic procedures was associated with the use of sedatives, worry score, depression score, and score for concern about health consequences. For anxiety following diagnostics, predictors included rural place of residence, depression score, history of spontaneous abortion, and score for tension and discomfort during colposcopy. The ANN models yielded highly accurate anxiety prediction both prior and after diagnostics, 76.47% and 85.30%, respectively. CONCLUSION: The presented findings can aid in identification of those women with a positive Pap screening test who could develop anxiety and thus represent the target group for psychological support, which would consequently improve adherence to follow-up diagnostics and enable timely treatment, finally reducing complications and fatal outcome.

Impact of colposcopy-guided carbon dioxide laser vaporization therapy on peripheral cervical intraepithelial neoplasia lesions.

OBJECTIVE: Laser vaporization is less invasive than conization for cervical intraepithelial neoplasia (CIN). The outcome of laser vaporization for CIN is empirically known to depend on the colposcopic findings, especially localization of the lesion. In this study, we sought to identify factors involved in the outcome of laser vaporization. MATERIALS AND METHODS: We retrospectively investigated 290 cases of CIN (CIN2, n = 180; CIN3, n = 110) treated with laser evaporation at Nishikawa Women's Health Clinic between 2018 and 2021. All treatments were performed using a carbon dioxide laser under either colposcopic vision (n = 172) or direct vision using a vaginal speculum (n = 118). Risk factors were statistically examined for cure rate after treatment. RESULTS: Multivariate analysis using a logistic regression model identified independent factors affecting the success of treatment to be high-risk human papillomavirus infection status preoperatively, CIN grade, presence of CIN lesions at the periphery of the cervix, and the surgical method used. Colposcopy-guided laser vaporization reduced the risk of treatment failure by 84% (odds ratio 0.16, 95% confidence interval 0.06-0.46; p = 0.001) compared with direct vision using a vaginal speculum. For lesions at the periphery of the cervix, most of the treatment failures were in the group that was not guided by colposcopy (p = 0.031). CONCLUSION: The presence of a peripheral CIN lesion was suggested to be a risk factor for treatment failure. Laser vaporization under colposcopic vision is recommended for treatment of peripheral CIN lesions.

Digital colposcopy image analysis techniques requirements and their role in clinical diagnosis: a systematic review.

INTRODUCTION: Colposcopy is a medical procedure for detecting cervical lesions. Access to devices required for colposcopy procedures is limited in low- and middle-income countries. However, various existing digital imaging techniques based on artificial intelligence offer solutions to analyze colposcopy images and address accessibility challenges. METHODS: We systematically searched PubMed, National Library of Medicine, and Crossref, which met our inclusion criteria for our study. Various methods and research gaps are addressed, including how variability in images and sample size affect the accuracy of the methods. The quality and risk of each study were assessed following the QUADAS-2 guidelines. RESULTS: Development of image analysis and compression algorithms, and their efficiency are analyzed. Most of the studied algorithms have attained specificity, sensitivity, and accuracy which range from 86% to 95%, 75%-100%, and 100%, respectively, and these results were validated by the clinician to analyze the images quickly and thus minimize biases among the clinicians. CONCLUSION: This systematic review provides a comprehensive study on colposcopy image analysis stages and the advantages of utilizing digital imaging techniques to enhance image analysis and diagnostic procedures and ensure prompt consultations. Furthermore, compression techniques can be applied to send medical images over media for further analysis among periphery hospitals.

Risk-stratified management of cervical high-grade squamous intraepithelial lesion based on machine learning.

The concordance rate between conization and colposcopy-directed biopsy (CDB) proven cervical high-grade squamous intraepithelial lesion (HSIL) were 64-85%. We aimed to identify the risk factors associated with pathological upgrading or downgrading after conization in patients with cervical HSIL and to provide risk-stratified management based on a machine learning predictive model. This retrospective study included patients who visited the Obstetrics and Gynecology Hospital of Fudan University from January 1 to December 31, 2019, were diagnosed with cervical HSIL by CDB, and subsequently underwent conization. A wide variety of data were collected from the medical records, including demographic data, laboratory findings, colposcopy descriptions, and pathological results. The patients were categorized into three groups according to their postconization pathological results: low-grade squamous intraepithelial lesion (LSIL) or below (downgrading group), HSIL (HSIL group), and cervical cancer (upgrading group). Univariate and multivariate analyses were performed to identify the independent risk factors for pathological changes in patients with cervical HSIL. Machine learning prediction models were established, evaluated, and subsequently verified using external testing data. In total, 1585 patients were included, of whom 65 (4.1%) were upgraded to cervical cancer after conization, 1147 (72.4%) remained having HSIL, and 373 (23.5%) were downgraded to LSIL or below. Multivariate analysis showed a 2% decrease in the incidence of pathological downgrade for each additional year of age and a 1% increase in lesion size. Patients with cytology > LSIL (odds ratio [OR] = 0.33; 95% confidence interval [CI], 0.21-0.52), human papillomavirus (HPV) infection (OR = 0.33; 95% CI, 0.14-0.81), HPV 33 infection (OR = 0.37; 95% CI, 0.18-0.78), coarse punctate vessels on colposcopy examination (OR = 0.14; 95% CI, 0.06-0.32), HSIL lesions in the endocervical canal (OR = 0.48; 95% CI, 0.30-0.76), and HSIL impression (OR = 0.02; 95% CI, 0.01-0.03) were less likely to experience pathological downgrading after conization than their counterparts. The independent risk factors for pathological upgrading to cervical cancer after conization included the following: age (OR = 1.08; 95% CI, 1.04-1.12), HPV 16 infection (OR = 4.07; 95% CI, 1.70-9.78), the presence of coarse punctate vessels during colposcopy examination (OR = 2.21; 95% CI, 1.08-4.50), atypical vessels (OR = 6.87; 95% CI, 2.81-16.83), and HSIL lesions in the endocervical canal (OR = 2.91; 95% CI, 1.46-5.77). Among the six machine learning prediction models, the back propagation (BP) neural network model demonstrated the highest and most uniform predictive performance in the downgrading, HSIL, and upgrading groups, with areas under the curve (AUCs) of 0.90, 0.84, and 0.69; sensitivities of 0.74, 0.84, and 0.42; specificities of 0.90, 0.71, and 0.95; and accuracies of 0.74, 0.84, and 0.95, respectively. In the external testing set, the BP neural network model showed a higher predictive performance than the logistic regression model, with an overall AUC of 0.91. Therefore, a web-based prediction tool was developed in this study. BP neural network prediction model has excellent predictive performance and can be used for the risk stratification of patients with CDB-diagnosed HSIL.

Optimization of HPV-positive women triage with p16/Ki67 dual staining cytology in an organized cervical cancer screening program in the center region of Portugal.

BACKGROUND: Organized cervical cancer (CxCa) screening is the most effective secondary prevention method to decrease the disease incidence and mortality. Screening for infection with 14 high-risk HPV genotypes (hrHPV) is recommended as primary screening test. Since only ca. 6 % of HPV-positive (HPV+) women will develop a high-grade lesion in 5 years, triage is critical for risk stratification and management of colposcopy resources. Dual staining (DS) p16/Ki67 cytology is an alternative to Papanicolau cytology (PAP) for triage of HPV+women, with potential improvements in sensitivity and specificity, and optimization of colposcopy referrals. OBJECTIVES: To compare PAP vs DS cytology in terms of (i) optimization of referrals for colposcopy and (ii) risk stratification to better define the follow-up interval. STUDY DESIGN: Retrospective analysis of the CxCa screening database of Centro Hospitalar Universitário de Coimbra (CHUC), one of the centralized diagnostic laboratories for the CxCa screening program of the central region of Portugal, between July 2019 and May 2023. At CHUC, since July 2019, all samples from hrHPV+women have been triaged with liquid PAP and tested with DS cytology. RESULTS: At baseline (1032 HPV+women), 1028 women were tested with DS: 739 women were DS negative (DS-) [70.7 % with normal PAP cytology (NILM) and 29.3 % with abnormal PAP cytology (ASC-US+)], and 289 were DS positive (DS+) (1.1 % NILM and 98.6 % ASC-US+). DS positivity as referral criterion for colposcopy instead of ASC-US+would have reduced the number of colposcopies by 39.4 % overall and by 48.3 % for other 12 hrHPV, while improving the number of colposcopies per HSIL (3.9 vs. 2.4 overall and 4.9 vs. 2.9 for other 12 hrHPV). In this cohort, if the follow-up interval for women positive for other 12 hrHPV+and DS- would have been extended from 1 to 3 years, 799 follow-up consultations, 799 HPV re-tests, and 277 colposcopies (-64.7 %) would have been avoided, with an overall risk of missed HSIL lesions of 2.2 %. CONCLUSIONS: Triage with DS allows the optimization of colposcopy referrals and a safe extension of the follow-up interval to 3 years for other 12 hrHPV+/DS- women, eliminating the need for annual re-testing for many women.

Usability of a smartphone-compatible, confocal micro-endoscope for cervical cancer screening in resource-limited settings.

BACKGROUND: More efficient methods to detect and treat precancerous lesions of the cervix at a single visit, such as low-cost confocal microscopy, could improve early diagnosis and hence outcomes. We piloted a prototype smartphone-compatible confocal micro-endoscope (SCME) among women presenting to a public cervical cancer screening clinic in Kampala, Uganda. We describe the piloting of the SCME device at an urban clinic used by lower cadre staff. METHODS: We screened women aged 18 and 60 years, who presented for cervical cancer screening at the Kawempe National Referral Hospital Kampala, and evaluated the experience of their providers (nurses). Nurses received a 2-day training by the study doctors on how to use the SCME, which was added to the standard Visual Inspection with Acetic acid (VIA)-based cervical cancer screening. The SCME was used to take colposcopy images before and after VIA at positions 12 and 6 O'clock if VIA negative, and on precancer-suspicious lesions if VIA positive. We used questionnaires to assess the women's experiences after screening, and the experience of the nurses who operated the SCME. RESULTS: Between November 2021 and July 2022, we screened 291 women with a median age of 36 years and 65.7% were HIV positive. Of the women screened, 146 were eligible for VIA, 123 were screened with the SCME, and we obtained confocal images from 103 women. Of those screened with the SCME, 60% found it comfortable and 81% were willing to screen again with it. Confocal images from 79% of the women showed distinguishable cellular features, while images from the remaining 21% were challenging to analyze. Nurses reported a mean score of 85% regarding the SCME's usefulness to their work, 71% regarding their satisfaction and willingness to use it again, 63% in terms of ease of use, and 57% concerning the ease of learning how to operate the SCME. CONCLUSION: Our findings demonstrate the feasibility of using the SCME by lower cadre staff in low-resource settings to aid diagnosis of precancerous lesions. However, more work is needed to make it easier for providers to learn how to operate the SCME and capture high-quality confocal images.

Comment on: Effect of Pap Smear Cytology, HPV Genotyping On the Concordance of Colposcopy and Conization Results.

Null.

Prognostic factors for low- and high grade squamous intraepithelial lesions in histological preparations following LLETZ procedure.

OBJECTIVE: Aim: To investigate the influence of the following prognostic factors: age, parity, hormonal status (premenopausal, postmenopausal), histological result from targeted biopsy (LSIL, HSIL), adequacy of colposcopic examination (satisfactory, unsatisfactory colposcopy), type of TZ (type 1, 2, 3), type of cervical lesions (type 1, 2, 3), the colposcopic impression (diagnosis) of the cervical lesion (LSIL, HSIL/Ca colli uteri in situ), lesion size (up to 1/3; up to 2/3; more than 2/3 of the cervical circumference) for the occurrence of LSIL and HSIL/Ca colli uteri in situ in the final histological result after LLETZ procedure. PATIENTS AND METHODS: Materials and Methods: This is a prospective study (01.01.2017 - 31.07. 2021) including 189 patients with cervical precancerous lesions received LLETZ treatment One gynaecologic oncologist performed video colposcopy, targeted biopsy, and LLETZ. One histopathologist diagnosed histological specimens from the biopsy and LLETZ procedure. RESULTS: Results: We found a statistically significant correlation between the histological result of the targeted biopsy factor and the colposcopic diagnosis factor concerning the final histological result of LLETZ. The cervical lesion size factor and cervical lesion type factor have prognostic significance for the histological outcome following LLETZ. CONCLUSION: Conclusions: The histological result of targeted biopsy and colposcopic diagnosis are significant factors for the final histological result after LLETZ. Cervical lesion invasion into the endocervical canal is a prognostic factor for HSIL, and its invisible borders - for carcinoma (in situ or microinvasive/invasive). Lesion size up to 1/3 of the cervix is a prognostic factor for LSIL and large lesions (2/3 of the cervix) - for HSIL and cervical cancer (in situ, microinvasive/invasive).

Transition from opportunistic cytological to organized screening program with DNA-HPV testing detected prevalent cervical cancers 10 years in advance.

Cervical cancer screening in Brazil is opportunistic, based on cytology and offered for women aged 25-64 years, with low coverage (30%) and 70% of cancer diagnoses done in advanced stages, without impact on mortality. The current study reports 5-year first-round results of a population-based DNA-HPV testing screening program in a Brazilian city, which intended to be a model for transition to a more efficient program. Program flowchart is simple and current, indicating repetition of a negative test after five years. The first-round (October 2017-September 2022) screened 20,551 women by DNA-HPV testing with 58.7% coverage and 99.4% compliance with the program's targeted age range. Coverage increases to 77.8% when excluding the 'pandemic period'. The DNA-HPV testing was 87.2% negative with 6.2% colposcopy referrals and 84.8% colposcopies performed. A total of 258 high-grade precursor lesions and 29 cervical cancers (mean age = 41.4 years, 83% Stage I) were detected. As a reference, 41,387 cytology tests from the previous program (2012-2016) detected 36 cervical cancers (mean age = 52.0 years, p = 0.0005), with 67% in advanced stages (p < 0.0001). Organizing cervical cancer screening using DNA-HPV testing demonstrated good coverage, high age and colposcopy compliance, and detection of more precancerous lesions and cervical cancers 10 years in advance.

Age-specific performance of human papillomavirus E6/E7 mRNA assay versus cytology for primary cervical cancer screening and triage: community-based screening in China.

Background: In the general population, primary human papillomavirus (HPV) testing is advocated for cervical cancer (CC) screening. HPV E6/E7 mRNA (Aptima HPV, AHPV) assays have garnered considerable traction due to their higher specificity when compared with HPV DNA assays. Here, we investigated age-specific primary AHPV screening assays and different triage strategies versus cytology to identify the best approach. Methods: Between April 2018 and December 2021, we recruited female participants from 34 communities across Liaoning province and Qingdao City, China. Primary cervical screening protocols included liquid-based cytology (LBC) and AHPV assays, with females positive for any assays undergoing colposcopy. Genotyping (AHPV-GT) was conducted on all HPV-positive samples. Our primary outcomes were the identification of age-specific detection rates, colposcopy referral rates, and sensitivity and specificity values for high-grade squamous intraepithelial lesions or worse (HSIL+). AHPV and different triage strategy performances were also examined across different age cohorts. Results: Our investigation included 9911 eligible females. Age-specific abnormal cytology rates were in the 6.1%-8.0% range, and were highest in 45-54-year olds. When compared with 35-44-or 45-54-year olds, HPV prevalence was highest in 55-64-year olds (12.2% or 11.6% vs.14.1%, P = 0.048 and P = 0.002, respectively). In 35-44-year olds, AHPV sensitivity for detecting HSIL+ was 96.6 (95% confidence interval [CI]: 89.7-100) - significantly higher than LBC sensitivity (65.5 [95% CI: 48.3-82.8], P < 0.001). When compared with LBC, HSIL+ detection rates by AHPV-GT using reflex LBC triage increased by 31.5% (9.6‰ vs. 7.3‰), and colposcopy referral rates decreased by 16.4% (5.1% vs. 6.1%). In 45-54-year olds, HSIL+ detection rates for AHPV-GT using reflex LBC triage were lower than LBC rates (6.2‰ vs. 6.6‰). In 55-64-year olds, AHPV sensitivity (97.2 [95% CI: 91.7-100.0]) was higher than LBC sensitivity (66.7 [95% CI: 50.0-80.6], P = 0.003). The area under the curve (AUC) value was not significantly different between AHPV-GT with reflex LBC triage and LBC (0.845 [95% CI: 0.771-0.920] vs. 0.812 [95% CI: 0.734-0.891], P = 0.236). Conclusions: Primary AHPV screening using different triage strategies were different across different age cohorts. Thus, AHPV may be an appropriate primary screening method for 35-44 and 55-64 year old females, while AHPV-GT with reflex LBC triage may be more apt for 35-44 year old females.

Development and pilot implementation of a novel protocol to assess capacity and readiness of health systems to adopt HPV detection-based cervical cancer screening in Europe.

BACKGROUND: Cervical cancer remains a significant public health concern in Europe. Effective introduction and scaling up of human papillomavirus (HPV) detection-based cervical cancer screening (CCS) requires a systematic assessment of health systems capacity. However, there is no validated capacity assessment methodology for CCS programmes, especially in European contexts. Addressing this gap, our study introduces an innovative and adaptable protocol for evaluating the capacity of CCS programmes across varying European health system settings. METHODS: Our research team developed a three-step capacity assessment framework, incorporating a health policy review checklist, a facility visit survey, and key informants' interview guide followed by a strengths, weaknesses, opportunities and threats (SWOT) analysis. Piloting this comprehensive approach, we explored the CCS capacity in three countries: Estonia, Portugal and Romania. These countries were selected due to their contrasting healthcare structures and resources, providing a diverse overview of the European context. RESULTS: Conducted over a period of 9 months, the capacity assessment covered multiple resources, 27 screening centres, 16 colposcopy and treatment centres and 15 key informant interviews. Our analysis highlighted both shared and country-specific challenges. A key common issue was ensuring high compliance to follow-up and management of screen-positive women. We identified considerable heterogeneity in resources and organization across the three countries, underscoring the need for tailored, rather than one-size-fits-all, solutions. CONCLUSIONS: Our study's novelty lies in the successful development of this capacity assessment methodology implementable within a relatively short time frame, proving its feasibility for use in various contexts and countries. The resulting set of materials, adaptable to different cancer types, is a ready-to-use toolkit to improve cancer screening processes and outcomes. This research marks a significant stride towards comprehensive capacity assessment for CCS programmes in Europe. Future directions include deploying these tools in other countries and cancer types, thereby contributing to the global fight against cancer.

The efficacy and safety of cervical polypectomy with vaginoscopy in pregnant women.

PURPOSES: This study aims to assess the effectiveness and safety of cervical polypectomy performed via vaginoscopy in pregnant women. METHODS: Pregnant patients diagnosed with cervical polyps were retrospectively included in Beijing Tiantan Hospital between April 2017 and April 2023. Group A underwent cervical polypectomy using a vaginoscopy technique without speculum, cervical forceps and anesthesia, while Group B received conservative management. The incidence of spontaneous abortion, preterm birth, preterm rupture of membranes (PROM), visual analog scale (VAS) scores, timing and method of delivery, and neonatal outcomes were analyzed. RESULTS: Of 90 pregnant patients included in the study, 48 patients receiving polypectomy under vaginoscopy were included into group A while 42 patients receiving conservative treatment were assigned into group B. At baseline, group A exhibited higher rates of vaginal bleeding pre-operation, as well as larger cervical polyp dimensions compared to group B. The median interval between vaginal bleeding and polypectomy was 3.5 weeks, with the median procedure typically performed at gestational week 19 in group A. There was no significant difference in the incidence of spontaneous abortion between the two groups (4.2% vs. 4.8%, p = 1.000). However, group A showed a significantly lower frequency of preterm birth (4.2% vs. 21.4%, p = 0.030) and premature rupture of membranes (PROM) (18.8% vs. 45.2%, p = 0.025) compared to group B. No disparities were observed in the timing, mode of delivery, and neonatal outcomes between the two groups. CONCLUSIONS: The utilization of vaginoscopy for cervical polypectomy has been shown to decrease the likelihood of preterm delivery and premature rupture of membranes in pregnant women with symptomatic cervical polyps. Therefore, performing cervical polypectomy via vaginoscopy without anesthesia provide a feasible and optimal ways in the management of this population.

HPV Extended Genotyping to Triage Abnormal Cervical Cancer Screens-Balancing the Harms and Benefits of an Additional Triage Test before Direct Colposcopy Referral.

The Netherlands' cervical cancer screening program transitioned to primary human papillomavirus (HPV) screening in 2017. After the introduction of HPV-based screening, the country saw increases in colposcopy referral rates and detections of low-grade lesions. In July 2022, genotyping was introduced, and those with borderline or mild dyskaryotic (BMD) cytologic abnormalities were only referred to colposcopy if positive for HPV type 16 or 18, and repeat screening otherwise. In this article, various strategies using extended genotyping (HPV16/18/31/33/45/52/58) as a triage test after an abnormal screen were explored using data from HPV-positive participants with normal or BMD cytology in the Population-Based Screening Study Amsterdam (POBASCAM) trial. The authors assessed positive and negative predictive values and colposcopy referral rates for each strategy using extended genotyping to triage women to either direct referral to colposcopy or repeat screening. Direct referral did not meet positive and negative predictive value thresholds for efficiency for any strategies. However, the authors note that direct referral may nonetheless be useful among those with BMD due to minimal increases in colposcopy referrals and concerns of loss to follow-up at repeat screening. These findings demonstrate the potential utility of extended genotyping as a triage test in primary HPV screening programs. The results should be considered alongside the fact that referral to repeat screening may result in loss of engagement of women who need treatment to prevent invasive cancer. See related article by Kroon et al., p. 1037.

Distribution and diagnostic value of single and multiple high-risk HPV infections in detection of cervical intraepithelial neoplasia: A retrospective multicenter study in China.

The risk associated with single and multiple human papillomavirus (HPV) infections in cervical intraepithelial neoplasia (CIN) remains uncertain. This study aims to explore the distribution and diagnostic significance of the number of high-risk HPV (hr-HPV) infections in detecting CIN, addressing a crucial gap in our understanding. This comprehensive multicenter, retrospective study meticulously analyzed the distribution of single and multiple hr-HPV, the risk of CIN2+, the relationship with CIN, and the impact on the diagnostic performance of colposcopy using demographic information, clinical histories, and tissue samples. The composition of a single infection was predominantly HPV16, 52, 58, 18, and 51, while HPV16 and 33 were identified as the primary causes of CIN2+. The primary instances of dual infection were mainly observed in combinations such as HPV16/18, HPV16/52, and HPV16/58, while HPV16/33 was identified as the primary cause of CIN2+. The incidence of hr-HPV infections shows a dose-response relationship with the risk of CIN (p for trend <0.001). Compared to single hr-HPV, multiple hr-HPV infections were associated with increased risks of CIN1 (1.44, 95% confidence interval [CI]: 1.20-1.72), CIN2 (1.70, 95% CI: 1.38-2.09), and CIN3 (1.08, 95% CI: 0.86-1.37). The colposcopy-based specificity of single hr-HPV (93.4, 95% CI: 92.4-94.4) and multiple hr-HPV (92.9, 95% CI: 90.8-94.6) was significantly lower than negative (97.9, 95% CI: 97.0-98.5) in detecting high-grade squamous intraepithelial lesion or worse (HSIL+). However, the sensitivity of single hr-HPV (73.5, 95% CI: 70.8-76.0) and multiple hr-HPV (71.8, 95% CI: 67.0-76.2) was higher than negative (62.0, 95% CI: 51.0-71.9) in detecting HSIL+. We found that multiple hr-HPV infections increase the risk of developing CIN lesions compared to a single infection. Colposcopy for HSIL+ detection showed high sensitivity and low specificity for hr-HPV infection. Apart from HPV16, this study also found that HPV33 is a major pathogenic genotype.

The role of endocervical curettage in the diagnosis of cervical intraepithelial neoplasia in human papillomavirus positive patients.

BACKGROUND: The role of endocervical curettage (ECC) in the diagnosis of cervical intraepithelial neoplasia (CIN) is a controversial topic. OBJECTIVES: Investigate the role of ECC in the diagnosis of CIN in human papillomavirus (HPV) positive patients. DESIGN: Retrospective. SETTING: A tertiary training and research hospital. PATIENTS AND METHODS: This study included patients who were referred for colposcopy between 2018-2022 because of abnormal screening results. ECC results, age, cytology, HPV status, and colposcopic impression of the patients were extracted from the medical records. Multinomial logistic regression analyses were performed to identify factors that could predict CIN on ECC. MAIN OUTCOME AND MEASURES: The likelihood of high-grade squamous intraepithelial lesions (HSIL) in ECC in patients with cervical biopsy results of normal and low-grade squamous intraepithelial lesion (LSIL). SAMPLE SIZE: 2895 women. RESULTS: In patients with normal and LSIL cervical biopsy results, HSILs were detected in 6.7% of ECC results. There was no difference in the detection rates of CIN in ECC among groups with smear results negative for intraepithelial lesions or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), and LSIL. The likelihood of HSIL being observed in ECC was 2.2 times higher in patients with HPV16. The probability of LSIL disanois was 2.3 times higher in women aged 50-59 years and 2.8 times higher in women ≥ 60 years compared to the reference group of <30 years. The probability of LSIL was 2.3 and HSIL by ECC was 2.2 times higher in both age categories (P<.012 and P=.032, respectively) than the reference group of <30 years. CONCLUSION: Regardless of colposcopic findings, ECC should be performed in patients with smear results of NILM who are positive for HPV16, in patients with smear results of ASC-US and LSIL who are positive for any oncogenic type of HPV and in patients 50 and above with any result of smear or any oncogenic HPV type. LIMITATIONS: We did not have the components of the HPV types in mixed groups.

The Impact of Tamoxifen Usage in Breast Cancer Patients on the Development of Histopathological Lesions in the Cervix Uteri.

Background and Objectives: The purpose of the present study was to compare the results of colposcopic biopsies in patients with breast cancer and those who tested positive for HPV in cervix uteri cytological screenings, with a control group of HPV-positive individuals without breast cancer. Additionally, through this study, we aimed to investigate the impact of tamoxifen treatment, an anti-oestrogen drug used following breast cancer treatment, on histopathological changes. Breast cancer is the most common type of cancer and cause of death in women worldwide. Cervical cancer ranks as the second most prevalent form of cancer among women globally, with prevalence rates ranking just behind those of breast cancer. Human papillomavirus (HPV) positivity is a requirement for the development of cervical cancer, although it is not the sole factor responsible. Materials and Methods: A comparison was made between the histopathological results of 52 patients diagnosed with breast cancer, who tested positive for HPV in routine cervical cytological screenings and underwent colposcopic biopsy, and 230 cases without any abnormalities. A study was conducted to compare healthy individuals between the ages of 30 and 65 who were diagnosed with breast cancer and those who did not have breast cancer. The participants underwent HPV screening as part of the national cervical cytology screening programme. Results: The average age of those diagnosed with breast cancer was 46.73 ± 7.54; in comparison, the average age of participants in the control group was 47.49 ± 7.95. There was no statistically significant difference in age between the two groups (p: 0.530). A total of 51 cases (98.1%) of breast cancer were found to have actively used the anti-oestrogen drug tamoxifen for a duration ranging from at least 6 months to 5 years. One patient (1.9%) in the breast cancer group did not use tamoxifen. During routine cervical cytological screenings, it was observed that both breast cancer cases and healthy cases tested positive for HPV. The most commonly detected types of HPV in both groups were HPV 16 and 18, with rates of 73.1% noted in the breast cancer group and 92.6% noted in the healthy group, results consistent with the rates found in the general population. HPV 16 was found in 58.7% of participants in the control group and 42.3% of participants in the breast cancer group. There was a statistically significant difference between the two groups (p: 0.032). There was no statistically significant difference observed between the two groups in terms of normal, high-grade cervical intraepithelial lesions (HGSILs); low-grade cervical intraepithelial lesions (LGSILs); and chronic cervicitis histopathological lesions based on colposcopic and endocervical biopsy results, smear cytology, and HPV results (p-values of 0.913 and 0.877, respectively). Conclusions: Our study results indicate that tamoxifen treatment, an anti-oestrogen drug administered for chemoprevention purposes in the management of breast cancer, does not lead to an increase in abnormal histological changes in the cervix uteri. In all cases of breast cancer, gynaecological examination and cervical cytological screening should be advised.

Does HPV-18 co-infection increase the risk of cervical pathology in individuals with HPV-16?

OBJECTIVE: We aimed to investigate differences between HPV-16 mono- and HPV-16/18 co-infections in terms of cervical dysplasia and invasive cancer. METHODS: This multicentre, retrospective study spanned from December 2017 to December 2020, involving women who visited gynaecological oncology clinics for colposcopy with either HPV-16 or HPV-16/18 positivity. A total of 736 patients, 670 in Group 1 (HPV-16 positivity) and 66 in Group 2 (HPV-16/18 positivity), were compared for the presence of CIN2+ lesions detected by colposcopic biopsy or endocervical curettage (ECC). Exclusions included hysterectomized patients, those with prior gynaecological cancers, and patients with HPV positivity other than types 16 and 18. RESULTS: Among the included patients, 42.4% had a diagnosis of CIN2+ lesions. The cytology results demonstrated abnormal findings in 45.3% in Group 1 and 42.2% in Group 2, with no significant difference between the groups. ECC revealed CIN2+ lesion in 49 (8.7%) patients in group 1, while only 1 (1.7%) patient had CIN2+ lesion in group 2. There was no difference between 2 groups in terms of ECC result (p = 0.052). In group 1, 289 (43.1%) patients had CIN2+ lesion, while 23 (34.8%) patients had CIN2+ lesions in group 2. There was no difference between group 1 and 2 in terms of diagnosis of CIN2+ lesions (p = 0.19). CONCLUSION: This multicentre retrospective study found no significant differences between HPV-16 mono- and HPV-16/18 co-infections regarding cervical pathologies. Larger studies are needed to validate and further explore these findings.