Comparative analysis between ideal and real cervical cancer screening in the city of Rio de Janeiro / Análise comparativa entre os rastreamentos ideal e real do câncer de colo uterino no município do Rio de Janeiro

Objective: to compare the number of planned oncotic smear tests and those actually performed in the city of Rio de Janeiro between the years 2013 and 2022 . Methods: using the female population of Rio de Janeiro, an estimate was made of how many tests should be carried out if screening recommended by the Ministry of Health was done in an ideal way and was subsequently compared with the number of tests available in the public database. Results: 1,364,325 were carried out in this period compared to an estimated 7,886,720. After adjustment for the use of supplementary healthcare, the pandemic and exams outside the recommended age, 36% of the ideal was observed. Conclusion: the quantity carried out is far below ideal, even after adjustments, which increases costs for the public health service, making new public policies necessary to improve tracking.

Objetivo: comparar el número de citologías oncóticas planificadas y las realizadas en la ciudad de Río de Janeiro entre los años 2013 y 2022 . Métodos: utilizando la población femenina de Río de Janeiro, se estimó cuántas pruebas se deberían realizar si se recomienda el tamizaje. realizado por el Ministerio de Salud se realizó de manera ideal y luego se comparó con la cantidad de pruebas disponibles en la base de datos pública. Resultados: En este periodo se realizaron 1.364.325 frente a una estimación de 7.886.720. Después del ajuste por el uso de asistencia sanitaria complementaria, la pandemia y los exámenes fuera de la edad recomendada, se observó el 36% del ideal. Conclusión: la cantidad realizada está muy por debajo de lo ideal, incluso después de ajustes, lo que aumenta los costos para el servicio público de salud, haciendo necesarias nuevas políticas públicas para mejorar el seguimiento.

Objetivo: comparar a quantidade de colpocitologias oncóticas ideias e a realmente realizadas no município do Rio de Janeiro entre os anos de 2013 e 2022. Métodos: através da população feminina do Rio de Janeiro, foi feita estimativa de quantos exames deveriam ser realizados caso o rastreio preconizado pelo Ministério da Saúde fosse feito de forma ideal e posteriormente foi comparado com a quantidade de exames disponíveis na base de dados pública. Resultados: foram realizados 1.364.325 nesse período comparado a 7.886.720 estimados. Após ajuste pelo uso de saúde suplementar, pandemia e exames fora da idade recomendada, observou-se 36% do ideal. Conclusão: a quantidade realizada está muito abaixo da ideal, mesmo após os ajustes, o que aumenta custos para o serviço de saúde pública, sendo necessárias novas políticas públicas para melhorar o rastreamento.

Tubal replacement of cervix for treatment of type II vaginal atresia complicated with cervical dysplasia: a case report.

Vaginal atresia is a rare obstructive disease of the reproductive tract. It is characterized by the absence or underdevelopment of the vaginal canal and results in various clinical manifestations. Hysterectomy can physically and mentally burden young female patients with a congenital cervix and complete vaginal atresia. This report presents a case of type II vaginal atresia complicated by cervical dysplasia in a female patient >10 years of age. Our team opted to preserve the patient's uterus, innovated a fallopian tube transplantation technique, and performed cervicovaginal reconstruction using natural channels instead of the cervical canal. The patient experienced menarche within the first 2 weeks postoperatively, and follow-up at 6 months revealed no abnormalities.

Impact of Excision Type, Cone Volume, and Dimensions on Persistence/Recurrence of Cervical Intraepithelial Neoplasia 2-3.

The objective of this study was to evaluate the relationship between the excision type and the persistence/recurrence of CIN2-3. A total of 227 women with CIN2-3 who were treated with LLETZ were evaluated. The types of excision according to the IFCPC 2011, volume, cone dimensions, margins of resection, post-cone high-risk human papillomavirus (HR-HPV) status, and viral load were studied. The time to recurrence was assessed using Kaplan-Meier curves. Persistent/recurrent CIN2-3 was found in 12 cases (5.2%). Type 1 excision was performed in 107 patients, with 7 recurrences (6.5%); type 2 excision in 74 patients, with 4 recurrences (5.4%); and type 3 excision in 46 patients, with 1 recurrence (2.1%). The percentage of clear margins in type 1 excisions was 44.9%, that in type 2 excisions was 59.5%, and that in type 3 excisions was 69.6% (p = 0.008). Type 1 excision was associated with 28.5% post-LLETZ HR-HPV positivity, that in type 2 reached 20.6%, and that in type 3 reached 11.4%; this difference was non-significant (p = 0.24). (4) Conclusions: Type 3 excision was associated with a larger proportion of clear margins and lower post-cone HR-HPV positivity, with a lower incidence of the persistence/recurrence of CIN2-3.

To cut or not to cut - that is the question: a comparative analysis of long-term follow-up after complete and incomplete electroconization of the cervix due to high-grade squamous intraepithelial lesion.

Introduction: Electroconization of the uterine cervix (LEEP/LLETZ) is an appropriate and sufficient procedure for high-grade squamous epithelial lesion - HSIL. Negative margins are considered fundamental for confirming the absence of residual disease. Further management after incomplete excision among women who have not completed their procreative plans is difficult because subsequent cervical procedures may cause issues with carrying a pregnancy to term. Since almost one-third of the untreated patients with HSIL will develop cervical carcinoma, it is essential to balance the desire to radicalize treatment with its obstetric consequences. We compared the further clinical course of the patients after complete and incomplete procedures to observe whether completeness of excision is necessary for a successful outcome. We aim to identify risk factors that influence persistent or recurrent HSIL. Methods: The study has comprised 781 patients aged 18-85 - the research group was composed of 140 (17.93%) patients after incomplete conization and the control group of 641 (82.17%) patients after the complete one. Patients were scheduled for follow-up examinations every 6 months - including cytology, HPV typing, and colposcopy with tissue sampling. The Chi-square test or Fisher's exact test was performed as a tool for group comparisons for variables on the qualitative scale. Univariable and multivariable logistic regression models have been used to determine factors associated with the risk of persistent or recurrent HSIL. To evaluate the discriminatory ability of the logistic regression models, the Area Under the Curve (AUC) was calculated. Results: The statistical analysis results don't indicate a statistical significance between the frequency of HSIL in groups. HPV infection has increased the risk of persistent/recurrent lesions by 38 times, constituting the most important factor. Discussion: Close follow-up instead of inconsiderate repeat procedures should be taken under consideration among patients of reproductive age after incomplete conization of the cervix. HPV typing may be an essential method to predict recurrent cervical dysplasia. Promoting HPV typing and vaccination can reduce the number of invasive procedures and improve quality of life and obstetrics outcomes.

Immediate risk of cervical intraepithelial neoplasia and diagnostic value of colposcopy among cytology-negative women with oncogenic HPV: a retrospective study.

BACKGROUND: Cervical cancer screening results that are negative for cytology but positive for high-risk human papillomavirus (HR-HPV) are not uncommon. One-year follow-up is suggested for patients with no history of HPV positivity under the most recent American Society of Colposcopy and Cervical Pathology (ASCCP) guidelines (2019). The aim of this study was to evaluate the immediate risk of cervical intraepithelial neoplasia (CIN) among cytology-negative patients positive for HR-HPV. The diagnostic accuracy of colposcopy in these patients was investigated. METHODS: A retrospective study was conducted in patients who were cytology negative but HR-HPV positive and referred for colposcopy from January 2022 to August 2023. Patients were compared in terms of the immediate rate of CIN lesions among the HPV16-positive group, the HPV18-positive group and the non-16/18 HR-HPV-positive group. The distribution of CIN2 + lesions according to age was evaluated. The factors associated with the accuracy of colposcopy were evaluated using univariate and multivariate logistic regression. RESULTS: Among the 372 patients, 195 had chronic cervicitis, 131 had CIN1, 37 had CIN2/3, and nine had carcinoma. The immediate rates of CIN2 + lesions and CIN3 + lesions in patients who were not HR-HPV16/18-positive were comparable to those in patients who were HPV16/18-positive (P = 0.699). In addition, among patients diagnosed with CIN2 + lesions, 8 (17.39%) patients were women aged < 30 years. When pathological results were used as a reference, the consistency rate of colposcopy was 61.0% (227/372). Multivariate analyses revealed that age and the type of cervical transformation zone were independent factors affecting the accuracy of colposcopy (P < 0.001). CONCLUSIONS: In countries with limited resources, immediate colposcopy referral should be recommended for patients who are cytology negative but HR-HPV-positive (including non-16/18 HR-HPV-positive), and cervical cancer screening via cotesting should be suggested for women aged < 30 years. Colposcopy has moderate diagnostic value and can be affected by age and the type of cervical transformation zone.

The Effect of Random Biopsy and Endo-Cervical Curettage in Diagnosis of Precancerous Cervical Lesions in Women With Normal Colposcopy.

Objective: This study aimed to evaluate the effect of random biopsy and endo-cervical curettage (ECC), alone and together, in the diagnosis of high-grade cervical lesions in women with normal colposcopy. Materials and methods: This cross-sectional study was conducted on 356 women who underwent colposcopy examination in the gynecology-oncology clinic of Roointan-Arash Women's Hospital, affiliated with Tehran University of Medical Sciences. All eligible women underwent colposcopy. In colposcopy examination, up to four biopsy samples were randomly taken for each quartile of the cervix and ECC was performed. Finally, the rate of intraepithelial neoplasia (CIN) and the relation between random biopsy and ECC and CIN diagnosis was determined. Results: In total, 27 (7.6%) low-grade squamous intraepithelial lesions (LSIL) and 19 (5.3%) high-grade squamous intraepithelial lesions (HSIL) were detected in cases that underwent random biopsy. There was a significant association between the abnormal random biopsy results and having multiple sexual partners (p=0.001), cigarette (p=0.041), and hookah (p=0.033) smoking. Furthermore, 31 (8.7%) LSIL and 42 (11.8%) HSIL were reported in women who underwent ECC. There was a significant relation between the abnormal results of ECC and hookah consumption (p=0.008) and human papillomavirus (HPV) infection (p=0.011). The concordance (p=0.001) between random biopsy and ECC result was 71.2% and only in 28.8% of the cases one of the methods was normal and the other was abnormal. Conclusion: The present study showed that the simultaneous use of ECC and random biopsy in women with normal colposcopy increases the detection rate of precancerous lesions by up to 28.8%.

Visual Inspection with Acetic Acid Positivity in Screening and Early Detection of Cervical Dysplasia in Africa, 2023: A Meta-Analysis.

Background: Visual Inspection with Acetic acid (VIA) is the best feasible method of screening and early detecting for cervical dysplasia for resource limited settings like Africa. There is no study that can represent Africa on VIA positivity. Therefore, this metaanalysis was planned to verify the best available articles to pool the visual inspection with acetic acid positivity in screening and early detection of cervical dysplasia in Africa. Methods: The Cochrane Library, Web of Science, PubMed, Scopus, free Google database search engines, Google Scholar, and Science Direct databases were used to conduct a true search of this research article. STATA version 14.0 was used to do the metaanalysis. This meta-analysis was registered in PROSPERO database under the identity pf CRD42023392197. Result: This meta-analysis analyzed data from 21,066 women who had VIA examination to estimate the pooled VIA positivity in Africa. The overall pooled effect estimate of VIA positivity in Africa was 11.93 (95%CI: 11.48-12.37). Age <16 year during first intercourse 2.58(95%CI: 1.53-3.62), lifetime sexual partner ≥2 3.92(95%CI: 2.05-5.78) and HIV positivity 2.92(95%CI: 1.72-4.12) were the significant variables which influence VIA positivity. Conclusion: Overall pooled effect estimate of VIA positivity in Africa was high compared to other continents. The main factors that affect VIA positivity are age at first sexual contact being under 16 years old, the number of lifetime sexual partners being at least two, and HIV positivity. Therefore, the WHO's goal of creating Africa free of cervical cancer is still one that requires significant effort.

Prognostic outcome of cervical laser ablation using a holmium yttrium-aluminum-garnet (Ho:YAG) laser for the treatment of cervical intraepithelial neoplasia: A single-center retrospective study.

Objective: Although cervical conization is considered a standard treatment for cervical intraepithelial neoplasia (CIN) 2/3, laser ablation can compensate for the disadvantages of the former. CO2, semiconductor, and holmium yttrium-aluminum-garnet (Ho:YAG) lasers are applied in ablation, but no previous studies have shown the effectiveness of any of these techniques. Here, we retrospectively analyzed the application of the Ho:YAG laser in our hospital to verify its efficacy, and discussed the methods for optimal recurrence detection. Methods: We evaluated the recurrence rates of the pathological condition in patients who underwent laser ablation with a Ho:YAG laser for CIN2/3 at our institution from June 2012 to November 2021. We defined the recurrence as histologically confirmed CIN2 or more advanced stage. Age, preoperative diagnosis, human papillomavirus (HPV) genotype, and postoperative high-risk HPV status were recorded to establish their association with recurrence rates. Results: We performed surgery in 607 patients and the 2-year recurrence rate after interventions was 5.6%. Five patients were diagnosed with invasive cancer at the time of recurrence. Older age significantly correlated with higher risk of recurrence, but preoperative CIN grade and preoperative HPV 16/18 status did not significantly affect it. The postoperative high-risk HPV test was 100% sensitive for detecting recurrence. Conclusions: Laser ablation with the Ho:YAG laser yields promising results. Together with postinterventional management, high-risk HPV test after laser ablation should be conducted after diagnostic conization.This study received the approval from the Ethics Committee of the NHO Tokyo Medical Center (Ethics Committee approval number: R22-067).

Comparing Cervical Cancer Screening Strategies in an Incarcerated Population.

Objective: To describe the prevalence of cervical intraepithelial neoplasia (CIN), high-risk human papillomavirus (hrHPV) infection, and cervical cancer in a high-risk, underscreened incarcerated population and to evaluate the performance of current cervical cancer screening options to detect cervical precancer (CIN 2/3) in this population. Study Design: Deidentified data were obtained from all cytological, hrHPV DNA, and histopathological testing of cervical biopsies performed on people incarcerated at the North Carolina Correctional Institute for Women between January 1, 2013, and December 31, 2020. These were linked to corresponding demographic data. The proportions of histopathological diagnoses of CIN2+ and CIN3+ immediately preceded by abnormal cytology testing or hrHPV testing were determined, and prevalence differences and 95% confidence intervals were calculated. Results: A total of 15,319 individuals incarcerated at the North Carolina Correctional Institute for Women had at least one cytology result during 2013-2020. Of these, 2,829 (18%) had abnormal cervical cytology, and 3,724 (24.3%) had positive hrHPV testing. The detection of CIN2+ was 95.9% by preceding abnormal cervical cytology, 89.9% by preceding positive hrHPV testing (p = 0.03), and 96.5% by preceding positive co-testing. The detection rate of CIN3+ was 96.6% by preceding abnormal cervical cytology, 90.8% by preceding positive hrHPV testing (p = 0.12), and 96.6% by positive co-testing. Conclusion: In our sample, primary cytology and co-testing detected CIN2+ at higher rates when compared with primary hrHPV testing. This reinforces that incarcerated populations do not fall into average-risk populations for which current cervical cancer screening options are designed, which should be considered when performing screening in this population.

Prevalence of high-risk HPV and cervical dysplasia in IUD users and controls: a cross sectional study.

OBJECTIVE: To examine the prevalence of infections with high-risk human papillomavirus (HPV) and cervical dysplasia, and the clearance rate of HPV infections, in users of different kinds of intrauterine devices (IUDs) and other contraceptive methods. METHODS: A cross-sectional register-based study including 16,181 women aged 30-49 years participating in the screening programme for cervical cancer in a Swedish County in 2017-2018. Data on contraception from screening records was paired with the HPV test results, cytological and histological follow-up tests and subsequent HPV test. RESULTS: There was no difference in the risk of being HPV positive, or histological HSIL+, between users of copper-containing IUDs and women with no reported use of contraception. Use of levonorgestrel intrauterine system and hormonal contraception were associated with higher odds for HPV infection in age-adjusted models (aOR 1.21; 95% CI 1.04-1.41, and aOR 1.41; 95% CI 1.22-1.63, respectively) and for HSIL+ (aOR 1.45; 95% CI 1.02-2.06, and aOR 1.56; 95% CI 1.13-2.16, respectively). No significant differences were found in HPV clearance rates. CONCLUSIONS: Reported use of levonorgestrel intrauterine system and hormonal contraception, but not use of copper IUD, was associated with a higher prevalence of HPV infections and histological HSIL + compared to no reported use of contraception.

Women using copper IUD showed no difference in prevalence of HPV or cervical dysplasia compared to women not using contraception in cross-sectional study.

Topical imiquimod treatment of residual or recurrent cervical intraepithelial neoplasia lesions (TOPIC-2): A randomised controlled trial.

OBJECTIVE: To investigate the efficacy of imiquimod in women with residual or recurrent cervical intraepithelial neoplasia (rrCIN), compared with large loop excision of the transformation zone (LLETZ). DESIGN: Randomised controlled non-inferiority trial. SETTING: One academic and one regional hospital in the Netherlands. POPULATION: Thirty-five women with rrCIN were included in the study between May 2016 and May 2021. METHODS: Women were randomised to receive treatment with 5% imiquimod cream (12.5 mg) intravaginally (three times a week for a duration of 16 weeks) or a LLETZ procedure (standard treatment). MAIN OUTCOME MEASURES: The primary outcome was reduction to normal cytology at 6 months after starting treatment. Secondary outcomes were clearance of high-risk human papilloma virus (hr-HPV) in both groups and reduction to ≤CIN1 in the imiquimod group. Side effects were monitored. RESULTS: Treatment success was 33% (6/18) in the imiquimod group versus 100% (16/16) in the LLETZ group (P < 0.001), whereas HPV clearance was 22% (4/18) in the imiquimod group versus 88% (14/16) in the LLETZ group (P < 0.001). After the randomisation of 35 women, the futility of treatment with imiquimod was proven and the trial was prematurely finished. In the follow-up period, three patients remained without additional treatment, whereas all other patients underwent LLETZ, conisation or hysterectomy. In the LLETZ group none of the patients received additional treatment during 2 years of follow-up. CONCLUSIONS: This is the first randomised controlled trial to show that topical imiquimod has a significantly lower success rate in terms of reduction to normal cytology and hr-HPV clearance, compared with LLETZ, in women with rrCIN. Additionally, imiquimod has numerous side effects and after using imiquimod most women with rrCIN still required additional surgical treatment.

Human Papilloma Virus Typing as a Triage Tool for Women with Postcoital Bleeding: A Retrospective Cohort Study.

Objective: To investigate the performance of human papilloma virus (HPV) typing as a triage tool in the management of patients with postcoital bleeding (PCB). Methods: All patients referred for colposcopy at a cervical pathology clinic of a nationwide health insurance organization, due to PCB and had a preceding high-risk HPV (hrHPV) test between 2018 and 2020, were retrospectively located. Demographic and pathologic data were collected from electronic medical files. Sensitivity, specificity, and negative and positive predictive value of hrHPV test according to final pathology were calculated. Results: Three hundred ninety patients referred for colposcopy due to PCB with a preceding hrHPV test were located. HrHPV-positive patients were significantly younger (33.7 ± 10 vs. 37.2 ± 9, p < 0.006) with a higher proportion of nulliparous, nonmarried, and smokers compared with hrHPV-negative patients (75% vs. 47%, p < 0.001; 75.4% vs. 45.1%, p < 0.001; and 24.6% vs. 12.8%, p < 0.028, respectively). No case of high-grade cervical intraepithelial neoplasia (CIN2/3) was identified among hrHPV-negative patients. The sensitivity and NPV of the hrHPV test for high-grade cervical lesions were both 100%, decreasing to 36% and 95%, respectively, for any cervical dysplasia (CIN1/CIN2/CIN3). Adding cytology to HPV typing had a negligible effect on test performance. At univariate analysis, age, HPV vaccine status, nulliparity, and positive HPV typing were independently associated with cervical dysplasia. At multivariate analysis, only positive HPV typing remained significantly associated with cervical dysplasia (hazard ratio 2.75, confidence interval 1.1-6.5, p = 0.023). Conclusion: A negative HPV test even in the presence of PCB may rule out cervical dysplasia with extremely high accuracy and may save unnecessary colposcopies.

Comparative study of treatment efficacy in severe intraepithelial squamous cell lesions and preinvasive cervical cancer by conization and chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy.

BACKGROUND: Cervical cancer (CC) occupies a leading position in incidence among young women of reproductive age. In this connection, it is urgent to search for the most effective approaches to the diagnosis and treatment of this pathology. The purpose of the study was to evaluate the effectiveness of the PDT method using Cе6 with the control of the photobleaching using video and spectral fluorescence diagnostic methods, to develop the method of fluorescence-assisted systemic photodynamic therapy mediated with chlorin e6 for treatment CIN 3 and CIS. MATERIALS AND METHODS: A randomized comparative clinical study was conducted involving 94 women aged 18 to 49 years with histologically verified severe intraepithelial squamous cell lesions of the cervix or preinvasive cervical cancer. The patients were included in 2 groups: in the first group conization of the cervix was performed with curettage of the remaining part of the cervical canal; patients in the second group underwent the chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy. RESULTS: The absolute majority of patients in the main group after the first course of chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy showed normalization of cytological parameters and colposcopic picture, while women from the comparison group showed signs of cervical lesions statistically significantly more often. These changes corresponded to the dynamics of the proliferation markers expression in the cells of intraepithelial squamous cell lesions. Also, patients of the second group who were planning a pregnancy had better reproductive outcomes after treatment compared to those of the first group. CONCLUSION: In general, higher clinical efficacy and safety of the use of the chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy in the treatment of intraepithelial squamous cell lesions and preinvasive cervical cancer have been established compared to the use of standard treatment methods.

History of HPV in HPV-positive elderly women.

Background: The aim of this study was to examine the natural course of HPV infection in women of 60 years and older who were HPV positive at inclusion, and any association between HPV positivity in historical samples and dysplasia outcome. Methods: Eighty-nine women aged 60-82 years, who tested positive for HPV between 2012 and 2016 were included. Sampling for cytology and/or histology was also performed. HPV genotyping was carried out on archived material back to 1999. Results: Of the 89 HPV-positive women 16 had HSIL, 34 had LSIL and 39 were benign at inclusion. Of the women with HSIL, 50.0% had the same HPV type in the archive samples, 12.5% had another type, and 37.5% were HPV negative. Among the 34 women with LSIL, 47.1% had the same HPV type in archive samples, 5.8% had another type, and 47.1% were HPV negative. Of the 39 women without dysplasia at inclusion, 25.6% had the same HPV type in archive samples, 5.1% had another HPV type and 69.2% were HPV negative. Conclusion: Surprisingly few of the elderly women thus seem to have a history with the same or any HPV infection the years before being diagnosed with an HPV infection and dysplasia. The significance of an HPV infection for dysplasia development in elderly women is still not fully understood.

Vaginal dysbiosis seems associated with hrHPV infection in women attending the Dutch Cervical Cancer Screening Program.

Human papillomavirus (HPV) is a sexually transmitted virus, which infects approximately 80% of all men and women at some time in their lives. Usually, the infection is resolved successfully by the body's immune system. Persistent infection with high-risk HPV (hrHPV) is necessary but not sufficient for cervical cancer development, and additional factors, such as the vaginal microbiome (vaginome), are thought to be involved. The aim of this study is to investigate whether either vaginal dysbiosis (imbalance in vaginal bacterial composition) or sexually transmitted pathogens, e.g., Chlamydia trachomatis (CT), are possible cofactors for hrHPV infection and HPV-induced cervical dysplasia in asymptomatic women attending the Dutch Cervical Cancer Screening Program. In this study, 492 hrHPV-positive and 500 hrHPV-negative cervical smears from women attending the Screening Program were included. Age and cytology were known for the hrHPV-positive samples. All cervical smears were diluted in Aptima® specimen transfer medium and tested with Aptima® transcription-mediated amplification assays targeting CT, Neisseria gonorrhoeae (NG), Mycoplasma genitalium (MG), Candida spp. (CS), C. glabrata (CG), Trichomonas vaginalis (TV), and bacterial vaginosis (BV). The prevalences of CT, NG, MG, CS, CG, TV, and BV in this cohort were found to be 1.9%, 0.0%, 1.7%, 5.4%, 1.4%, 0.1%, and 27.2%, respectively. When comparing HPV groups, it was found that CT, MG, and BV had a significantly higher prevalence in hrHPV-positive smears as compared with hrHPV-negative samples (for all p < 0.001). No significant differences were found when comparing different age groups and cytology outcomes. In conclusion, vaginal dysbiosis seems associated with hrHPV infection in women attending the Dutch Cervical Cancer Screening Program.

A phase 1/2a, dose-escalation, safety, and preliminary efficacy study of the RKP00156 vaginal tablet in healthy women and patients with cervical intraepithelial neoplasia 2.

OBJECTIVE: This study aimed to determine the safety and efficacy of the RKP00156 vaginal tablet, a CDK9 inhibitor, in healthy women and patients with cervical intraepithelial neoplasia grade 2 (CIN2). METHODS: We conducted a phase 1/2a clinical trial of RKP00156. In step 1, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered transvaginally to 24 healthy women. In step 2, RKP00156 at a dose of 10, 25, or 50 mg or a placebo tablet was administered once daily for 4 weeks in 62 patients with CIN2. The primary endpoints of this trial were the safety of RKP00156 and the change in the human papillomavirus (HPV) viral load. RESULTS: A total of 86 patients were enrolled and randomized. RKP00156 administration did not cause serious drug-associated adverse events (AEs). Although no significant difference in the HPV viral load was found between the experimental and placebo groups, a reduction in the HPV viral load was observed in the 25 mg-dose group (-98.61%; 95% confidence interval=-99.83%, 4.52%; p=0.046) after treatment completion in patients with a high HPV viral load, despite a lack of statistical power. No differences in histologic regression and HPV clearance were observed. CONCLUSION: The safety of RKP00156 was proved with no serious AEs. Although the study did not show any significance in histologic regression and HPV clearance, our findings indicate that RKP00156 may have a possibility of short-term inhibitory effect on HPV replication in patients with higher viral loads. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02139267.

Hsa-miR-194-5p and hsa-miR-195-5p are down-regulated expressed in high dysplasia HPV-positive Pap smear samples compared to normal cytology HPV-positive Pap smear samples.

BACKGROUND: The human papillomavirus (HPV) infection may affect the miRNA expression pattern during cervical cancer (CC) development. To demonstrate the association between high-risk HPVs and the development of cervix dysplasia, we examined the expression patterns of hsa-miR-194-5p and hsa-miR-195-5p in Pap smear samples from southeast Iranian women. We compared samples that were HPV-positive but showed no abnormality in the cytological examination to samples that were HPV-positive and had severe dysplasia. METHODS: Pap smear samples were obtained from 60 HPV-positive (HPV-16/18) patients with histologically confirmed severe dysplasia (cervical intra-epithelial neoplasia (CIN 3) or carcinoma in situ) and the normal cytology group. The expression of hsa-miR-194-5p and hsa-miR-195-5p was analyzed by real-time quantitative PCR, using specific stem-loop primers and U6 snRNA as the internal reference gene. Clinicopathological features were associated with miRNA expression levels. Furthermore, functional enrichment analysis was conducted using in silico tools. The Kaplan-Meier survival method was also obtained to discriminate survival-significant candidate miRNAs in CC, and receiver operating characteristic (ROC) curves were constructed to assess the diagnostic value. RESULTS: Compared to HPV-positive cytologically normal Pap smear samples, hsa-miR-194-5p and hsa-miR-195-5p relative expression decreased significantly in HPV-positive patients with a severe dysplasia Pap smear. Kaplan-Meier analysis indicated a significant association between the miR-194 decrease and poor CC survival. In essence, ROC curve analysis showed that miR-194-5p and miR-195-5p could serve as valuable markers for the development of cervix dysplasia in individuals who are positive for high-risk HPVs. CONCLUSIONS: This study revealed that hsa-miR-194-5p and hsa-miR-195-5p may possess tumor suppressor capabilities in the context of cervical dysplasia progression. However, it remains uncertain whether these microRNAs are implicated in the transition of patients with high dysplasia to cervical cancer. We also showed the potential capability of candidate miRNAs as novel diagnostic biomarkers related to cervical dysplasia progression.

Impact of the Corona Pandemic on Cervical Cancer Screening Assessment.

BACKGROUND/AIM: The global impact of the COVID-19 pandemic resulted in disruptions to healthcare systems throughout the world. The numbers of cytology examinations, human papillomavirus (HPV) tests, and women referred for colposcopy decreased in many countries. There have been no reports on cervical cancer screening in Germany. This study aimed to describe changes in the numbers of colposcopies, cytology examinations, HPV tests, and histological results during the pandemic compared to the pre-pandemic years in order to evaluate the impact of the COVID-19 pandemic on cervical cancer screening. PATIENTS AND METHODS: The numbers of colposcopies, cytology examinations, HPV tests, and histologic results were analyzed retrospectively for the period January 2018 to December 2022. The 2 years period before the pandemic (2018 and 2019) were compared with the 3 years period of the pandemic (2020-2022). RESULTS: In total, 6,518 colposcopies were performed in 5,579 women. The numbers of colposcopies, cytology examinations, and high-risk HPV (hrHPV) tests increased during the pandemic years. The number of biopsies per year taken was stable (range=450-554). The relative numbers of cervical intraepithelial neoplasia (CIN) III/HSIL findings were stable, while the numbers of cervical cancers identified increased slightly from 15 (6.6%) in 2018 to 22 (7.4%) in 2022. CONCLUSION: Increases in numbers of women examined and colposcopies were observed in the years 2021 and 2022 during the pandemic, in comparison to the preceding years. These also led to increases in the figures for cytology, hrHPV, histology, and operations. The onset of the pandemic occurred in the same year as a newly organized screening program started in Germany. The increases might therefore be due to the newly organized screening system.

Factors associated with human papillomavirus persistence after loop electrosurgical excision procedure in patients with cervical squamous intraepithelial lesion.

AIM: To seek the high-risk factors of human papillomavirus (HPV) persistence and residual lesion or recurrence after loop electrosurgical excision procedure (LEEP) focus on the predictive value of intraoperative human papilloma virus (IOP-HPV) testing. METHODS: Intraoperative endocervical sample was obtained with a cytobrush from the remained cervix of 292 patients immediately after LEEP. HPV Genotyping was performed using a polymerase chain reaction technique. All patients followed by HPV genotyping and cytology every 3-6 months. The IOP-HPV testing results and possible risk factors such as age, cytology grade, menopause status, margin involvement, preoperative HPV status, and cervical lesion grade were assessed in predicting persistence of HPV and residual lesion or recurrence after surgery. RESULTS: There were 61 (20.9%) patients presented persistent HPV infection. Multivariate analyses showed that IOP-HPV positive, post-menopause and preoperative HPV multiplex infection was strongly associated with HPV persistence after LEEP, IOP-HPV positive and post-menopause was also associated with residua or recurrent disease after LEEP. CONCLUSIONS: IOP-HPV positive, post-menopause, and preoperative HPV multiplex infection are independent predictors of HPV persistence in patients with cervical squamous intraepithelial lesion treated by LEEP. IOP-HPV test is a new approach that may potentially allow for early identification of patients at high risk of HPV persistence and residua or recurrent disease after LEEP, thereby possibly facilitate an attenuated follow-up schedule for negative patients those at low risk of persistent HPV infection.

Persistent cervical cancer disparities among American Indian/Alaska Native women: a systematic scoping review exploring the state of the science in this population.

PURPOSE: American Indian/Alaska Native (AI/AN) populations experience significantly higher incidence and mortality rates of cervical cancer. The objective of this systematic scoping review is to characterize the volume and nature of research being conducted specific to the AI/AN population regarding cervical cancer and related clinical themes. METHODS: This scoping review was conducted in collaboration with the Pacific Northwest Evidence-based Practice Center. Search strategies identified eligible publications from 1990 through 4 February 2022. Two reviewers independently abstracted study data, including clinical area, number of participants and percent inclusion of AI/AN, intervention or risk factor, outcomes reported, Indian Health Service (IHS) Region, and funding source. We used published algorithms to assess study design. RESULTS: Database searches identified 300 unique citations. After full-text evaluation of 129 articles, 78 studies and 9 secondary publications were included (total of 87). Approximately 74% of studies were observational in design, with cross-sectional methodology accounting for 42.7% of all included studies. The most common clinical theme was cervical cancer screening. The most common intervention/exposure was risk factor, typically race (AI/AN compared with other groups) (69%). For studies with documented funding sources, 67% were funded by the US Government. CONCLUSION: Of the small number of publications identified, the majority are funded through government agencies, are descriptive and/or cross-sectional studies that are hypothesis generating in nature, and fail to represent the diversity of the AI/AN populations in the US. This systematic scoping review highlights the paucity of rigorous research being conducted in a population suffering from a greater burden of disease.