RESUMEN
BACKGROUND: Cytological screening remains a high-impact practice, particularly in low-resource settings, for preventing cervical cancer. The examination of screening practices over time and the prevalence of epithelial abnormalities have not been investigated in longitudinal studies in one of the largest countries in the Middle East and Africa. METHODS: Routine healthcare data, between March 1981 and December 2022, were extracted from the database of the Early Cancer Detection Unit in a tertiary referral university hospital in the Greater Cairo Region, Egypt. Cervical smears were obtained using a standardized technique and sent to the cytopathology laboratory for conventional cytology examination by expert pathologists. The anonymous data were analyzed to determine the temporal trend of the number of women screened each year and the prevalence of epithelial abnormalities. RESULTS: Data included the results of satisfactory smears from 95120 women. The mean age (SD) of the women at the time of screening was 38.5 (10.5). None of the included women received an HPV vaccine. Abnormal epithelial cells were reported in 5174 women (5.44%). Of these epithelial abnormalities, the majority were low-grade squamous intraepithelial lesions in 4144 women (4.36%). Other abnormalities included atypical squamous cells in 378 women (0.40%), high-grade squamous intraepithelial lesions in 226 women (0.24%), atypical glandular cells not otherwise specified in 184 women (0.19%), adenocarcinoma in 165 women (0.17%), squamous cell carcinoma in 70 women (0.07%), and atypical glandular cells favoring neoplasms in 7 women (0.01%). Women who were at an early age at first intercourse, those who opted for routine cervical cytology screening, and those who were older at screening were more likely to have epithelial abnormalities. The yearly number of screened women was positively associated with the detection of low-grade squamous intraepithelial lesions (correlation coefficient [95% CI] = 0.84 [0.72, 0.91]) and negatively associated with the detection of squamous cell carcinoma (correlation coefficient [95% CI] = -0.55 [-0.73, -0.29]). CONCLUSIONS: The small number of annually screened Egyptian women and the temporal trend in epithelial abnormalities critically demonstrate the need for establishing and scaling up a structured population-based program to achieve the goal of eliminating cervical cancer.
Asunto(s)
Detección Precoz del Cáncer , Centros de Atención Terciaria , Neoplasias del Cuello Uterino , Frotis Vaginal , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/epidemiología , Adulto , Detección Precoz del Cáncer/estadística & datos numéricos , Detección Precoz del Cáncer/métodos , Frotis Vaginal/estadística & datos numéricos , Centros de Atención Terciaria/estadística & datos numéricos , Persona de Mediana Edad , Egipto/epidemiología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/patología , Estudios Longitudinales , Prevalencia , Células Escamosas Atípicas del Cuello del Útero/patología , Tamizaje Masivo/métodos , Tamizaje Masivo/estadística & datos numéricos , Configuración de Recursos Limitados , CitologíaRESUMEN
Objectives: To probe cervical cancer screening practices in local women positive for human immunodeficiency virus, and to determine the cervical cytological changes in them. METHODS: The serial cross-sectional study was conducted at the Jinnah Hospital and Services Hospital, Lahore, Pakistan, from April 2019 to October 2020, and comprised female patients aged 18-45 years who were positive for human immunodeficiency virus or acquired immunodeficiency syndrome and were registered with the relevant programme being run by the provincial government in Punjab. Blood samples of all the patients were collected for the determination of human immunodeficiency virus viral load and cluster of differentiation 4+ count. Cervical smears were taken for cytopathological analysis, while the swabs were analysed for culture sensitivity. The same individuals were subjected to the same testing one year later, and the status of the disease and clinical stability or disease progression was explored. Data was analysed using SPSS 25. RESULTS: There were 150 women with mean age 32.08±7.13 years (range: 21-45 years). Age at marriage/sexual activity was 17.33±4.73 years in 15(10%) subjects. Cytological examination showed atypical squamous cells of undetermined significance in 6(4%) of the cases whereas 3(2%) cases showed atypical squamous cells, which cannot rule out high grade squamous intraepithelial lesion on cytology, while the rest were classified as negative for intraepithelial lesion or malignancy. Cervical microbial changes revealed methicillin-resistant staphylococcus aureus infection in 9(6%) cases, extended-spectrum beta-lactamase in 15(10%) cases, whereas fungal infection and trichomonas vaginalis infection were found in 30(20%) smears. There was a significant association between cluster of differentiation 4+ cell count and stability of high-risk patients (p<0.001). After one year, 84(56%) patients remained clinically stable, while 51(34%) developed some chronic illness. There was a significant association between cluster of differentiation 4+ cell count <200/mm3 and the risk of developing a chronic illness (p<0.001). CONCLUSIONS: There was a dire need to educate healthcare workers to offer regular cervical screening to patients with high-risk sexually-transmitted infections to prevent them from the morbidity and mortality related to cervical cancer.
Asunto(s)
Detección Precoz del Cáncer , Infecciones por VIH , Neoplasias del Cuello Uterino , Humanos , Femenino , Adulto , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Pakistán/epidemiología , Detección Precoz del Cáncer/métodos , Estudios Transversales , Adulto Joven , Persona de Mediana Edad , Infecciones por VIH/epidemiología , Infecciones por VIH/diagnóstico , Frotis Vaginal , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/virología , Células Escamosas Atípicas del Cuello del Útero/patología , Carga ViralRESUMEN
Human papillomavirus (HPV) is the most common sexually transmitted pathogen that causes anogenital disease. Cervical screening by cytology and HPV testing (co-testing) are important in prevention of cervical cancer. The Bethesda System category of atypical squamous cells (ASC) is used when a neoplastic process cannot be confidently identified. In such cases, the differential diagnosis is broad and includes benign conditions. Monitoring of ASC/SIL ratio is a commonly used laboratory quality assurance measure to prevent over- or under-use of this category. High risk human papillomavirus (hr-HPV) has been used in conjunction with the ASC/SIL ratio in determining whether a particular pathologist is over/under-using the indefinite category. However, the laboratory overall sample population prevalence rate of hr-HPV subtypes has not been previously examined for association with the ASC rate. In this study, the relationships between ASC/SIL ratio and hr-HPV prevalence rate and hr-HPV subtypes (16/18 and non-16/18) to the laboratory ASC prevalence were studied. The results demonstrate that HPV non-16/18 is the main subtype which is associated with ASC-US category. A large proportion of non-16/18 HPV-related cases are seen in young patients, which largely abates by the by fourth decade. In addition, there are differences in the ASC/SIL ratio for HPV 16/18 and non-16/18 types. The overall ASC/SIL ratio is an average of the ASC/SIL rate for the non-16/18 population and the HPV 16/18 population. Instead of basing the laboratory and practitioners' quality indicator solely on ASC/SIL ratio, the overall prevalence of HPV and its subtype ratio should also be reported as they are more reflective of laboratory performance.
Asunto(s)
Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Prevalencia , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Células Escamosas Atípicas del Cuello del Útero/patología , Células Escamosas Atípicas del Cuello del Útero/virología , Frotis Vaginal/métodos , Papillomavirus Humano 16/aislamiento & purificación , Virus del Papiloma Humano , CitologíaRESUMEN
INTRODUCTION: Liquid-based cytology (LBC) has replaced conventional smear (CS) in the world. In this study, through a series with a large number of cases, we aimed to make a comparison and general evaluation in all groups, primarily epithelial abnormalities, according to LBC and CS methods. This study was carried out in a private pathology laboratory located in a metropolitan city, where cytological materials sent from many clinics were examined. MATERIAL AND METHODS: There were 165,915 cases whose smears were examined between 2012 and 2020, most of them conventional (131,224 CS, 34,691 LBC). Cases were evaluated on the basis of the Bethesda 2014 classification and divided into sub-diagnostic categories after they were divided into two main groups as "with epithelial abnormalities" and "without." χ2 and Fischer's precision statistical tests were conducted using SPSS 23.0 package. In the CS process, cervical samples were obtained using an endocervical brush and a spatula. Cells were directly spread onto the slides and promptly fixed in 95% ethanol, followed by staining with the standard Papanicolaou stain. For LBC ThinPrep, cervical specimens were gathered using a cervix brush. The brush was washed in a vial and discarded. Finally, cells were isolated through vacuum filtration and transferred to the slide using air pressure. RESULTS: Squamous cell abnormalities (atypical squamous cells of undetermined significance [ASC-US], atypical squamous cells - cannot exclude high-grade squamous intraepithelial lesion [ASC-H], low-grade squamous intraepithelial lesion [LSIL], high-grade squamous intraepithelial lesion [HSIL], squamous cell carcinoma, atypical glandular cells of undetermined significance) were reported in 5,696 (3.43%) cases. ASC (ASC-US + ASC-H)/SIL ratio (1.36/2.04) was found to be 0.67 (recommended Bethesda ratio is <3). ASC-US (p < 0.001), ASC-H (p < 0.001), and HSIL(p < 0.001) detection rate of LBC was found to be significantly higher than CS. ASC-US (1.8/1.2), ASC-H (0.08/0.008), and HSIL (0.6/0.3) case ratios of LBC/CS were found to be significantly higher in LBC. LSIL (1.72/1.66) rate was similar. CONCLUSION: LBC is superior to CS in detecting epithelial lesions. In addition to being used as a screening method, it is clear that it makes a great contribution to reducing cervical carcinomas due to HPV typing. Definitive comments regarding comparison of methods on reactive changes and microorganism detection are challenging. Preanalytical factors might account for these situations.
Asunto(s)
Células Escamosas Atípicas del Cuello del Útero , Carcinoma in Situ , Carcinoma de Células Escamosas , Lesiones Intraepiteliales Escamosas , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Displasia del Cuello del Útero/patología , Frotis Vaginal/métodos , Citodiagnóstico/métodos , Neoplasias del Cuello Uterino/patología , Células Escamosas Atípicas del Cuello del Útero/patología , Carcinoma de Células Escamosas/patología , Carcinoma in Situ/patología , Prueba de PapanicolaouRESUMEN
BACKGROUND: Cervical cancer is a global public health problem with high mortality. Advances in screening programs for cervical cancer are considered key to eliminate cervical cancer. We aimed to examine the contribution of cell block analysis to the detection of epithelial cell abnormalities in cervical smear samples. METHODS: A total of 559 patients with suspected cervical pathology were examined, and their samples were analyzed by both liquid-based cytology (LBC) and cell blocks. The biopsy results of 149 out of the 559 patients were obtained. RESULTS: Of the 50 patients who were identified as HSIL by biopsy, only 12 were diagnosed as HSIL by the LBC method, 22 as LSIL, 12 as ASCUS, and 4 as ASC-H (p < 0.001). With the cell block analysis, results for these patients were: 20 HSIL, 17 LSIL, 7 NILM, 4 'unsatisfactory', and 2 ASC cases (p < 0.001). LBC detected only 1 of the 10 patients with biopsy-diagnosed tumors, while 7 of these were defined as HSIL, 1 as ASCUS and 1 as AGC. The results of cell block analysis in patients with biopsy-diagnosed tumors were as follows: 7 HSIL, 1 tumor, 1 ASC and 1 LSIL. CONCLUSIONS: Cell block analysis might be superior to LBC in terms of diagnostic accuracy in cervical pathologies, particularly in the detection of HSIL. However, both methods were similarly poor in diagnosing tumors. Cell blocks may improve diagnostic accuracy and can be a complementary method to LBC, while having the advantage of revealing histological architecture.
Asunto(s)
Células Escamosas Atípicas del Cuello del Útero , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Células Escamosas Atípicas del Cuello del Útero/patología , Citología , Citodiagnóstico/métodos , Biopsia , Displasia del Cuello del Útero/patologíaRESUMEN
OBJECTIVE: To determine the baseline and cumulative risk of cervical intraepithelial neoplasia (CIN)3 and invasive cervical cancer in participants referred to colposcopy with high-grade cytology and Asunto(s)
Adenocarcinoma in Situ
, Células Escamosas Atípicas del Cuello del Útero
, Carcinoma in Situ
, Carcinoma de Células Escamosas
, Infecciones por Papillomavirus
, Lesiones Intraepiteliales Escamosas
, Displasia del Cuello del Útero
, Neoplasias del Cuello Uterino
, Embarazo
, Humanos
, Femenino
, Neoplasias del Cuello Uterino/diagnóstico
, Neoplasias del Cuello Uterino/epidemiología
, Neoplasias del Cuello Uterino/patología
, Colposcopía
, Displasia del Cuello del Útero/patología
, Células Escamosas Atípicas del Cuello del Útero/patología
, Frotis Vaginal
, Infecciones por Papillomavirus/diagnóstico
, Papillomaviridae
RESUMEN
INTRODUCTION: Methylation analysis of the promoter region of tumor-suppressor genes has previously shown high sensitivity for detection of high-grade cervical intraepithelial neoplasia (CIN) and cancer. HPV-testing has a high sensitivity to identify women at risk to develop cancer, and has been implemented in cervical screening programs in several countries. But in most HPV-positive women the infection will clear and they will not develop cancer. Testing for methylation could help to identify women who have potentially progressive cervical disease and need closer follow-up. The goal of the present study was to investigate the potential use of methylation as a triage test of HPV-positive women in the screening program. MATERIAL AND METHODS: A collection of liquid-based cytology (LBC) samples from 106 women, collected between 4 months and 8 years before histologically confirmed cervical cancer or CIN3, was analyzed for hypermethylation of the human genes FAM19A4 and miR124-2. RESULTS: Methylation was detected in 45% (33/73) of normal LBC samples from women who later developed CIN3+, compared with 10% (3/31) of normal LBC samples from women without subsequent dysplasia (P = 0.0006). Overall, methylation was detected in 39% (14/36), 51% (19/37), 61% (14/23) and 70% (7/10) of LBC samples from women who later developed CIN3, adenocarcinoma in situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma (ADC), respectively. Positive methylation analysis was not significantly more frequent than abnormal cytology of atypical squamous cells of unclear significance or worse (ASCUS+) in LBC samples collected 4 months to 8 years before SCC or AIS; however, prior to the development of ADC, methylation was observed in 7/10 LBC samples, despite normal cytology. Overall, LBC samples collected before invasive cancer (ADC and SCC) were more frequently positive in the methylation analysis than in cytological analysis of ASCUS+ (P = 0.048). For LBC samples collected more than 2 years before the development of AIS, SCC or ADC, methylation analysis showed a higher positivity rate than cytology did. CONCLUSIONS: Testing for methylation of FAM19A4/miR124-2 as a triage for HPV-positive women would be useful to identify women at risk of cancer development, especially adenocarcinoma. Further studies are needed to estimate the cost-effectiveness before introducing methylation testing in the screening program.
Asunto(s)
Adenocarcinoma , Células Escamosas Atípicas del Cuello del Útero , Carcinoma de Células Escamosas , MicroARNs , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Cuello del Útero/patología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/genética , Detección Precoz del Cáncer , Frotis Vaginal , Displasia del Cuello del Útero/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Metilación , Papillomaviridae/genética , MicroARNs/genéticaRESUMEN
OBJECTIVE: This study aims to investigate the implementation rate and influencing factors of confirmatory tests for women with abnormal cervical cytology results in the Korean nationwide cervical cancer screening program. METHODS: The National Health Insurance Service (NHIS) database was utilized to identify all Korean women who have participated in the Korean nationwide cervical cancer screening program from January 2011 and December 2021 using the NHIS database. Multiple logistic regression analysis was performed to estimate the multivariate odds ratio and evaluate the patients' characteristics. RESULTS: The rate of abnormal Papanicolaou (Pap) smears showed an initial increase from 2011 to 2015 and subsequently reached a plateau after 2016. When examining specific subcategories, cases of atypical squamous cells of undetermined significance (ASC-US) increased from 28,546 cases (1.1%) in 2011 to 62,850 cases (1.7%) in 2021. In contrast, cases of HSIL and SCC declined from 3,535 cases (0.14%) to 2,763 cases (0.07%) and from 383 cases (0.01%) to 179 cases (0.005%), respectively. Furthermore, the implementation rate of confirmatory tests for women with abnormal cytology increased from 8,865 cases (21.0%) in 2011 to 39,045 cases (51.2%) in 2021. Regarding the specific subcategory of ASC-US, the number of confirmatory tests exhibited a substantial increase from 4,101 cases (14.4%) in 2011 to 30,482 cases (48.5%) in 2021. For SCC, there was no significant change, with 216 cases (56.4%) in 2011 and 102 cases (57.0%) in 2021. The implementation rate of confirmatory tests was found to be significantly associated with results of abnormal Pap smear, age, and residence. Notably, economic status did not emerge as a significant factor affecting the likelihood of undergoing confirmatory tests. CONCLUSIONS: The severity of abnormal Pap smear results is a reliable indicator of the probability of undergoing a confirmatory test. Additional endeavors are required to improve the implementation rate among women who have received abnormal Pap smear results.
Asunto(s)
Detección Precoz del Cáncer , Programas Nacionales de Salud , Prueba de Papanicolaou , Neoplasias del Cuello Uterino , Frotis Vaginal , Humanos , Femenino , Prueba de Papanicolaou/estadística & datos numéricos , Adulto , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Persona de Mediana Edad , República de Corea/epidemiología , Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/estadística & datos numéricos , Frotis Vaginal/estadística & datos numéricos , Anciano , Células Escamosas Atípicas del Cuello del Útero/patología , Bases de Datos Factuales , Adulto Joven , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/patologíaRESUMEN
PURPOSE: To our knowledge, there are very few studies evaluating if the levels of folate modify the risk of cervical intraepithelial neoplasia grade 2 and higher (CIN2+ and CIN3+) associated with the levels of HPV genome methylation, two cofactors related to single carbon metabolism and independently associated with cervical cancer in previous studies. We conducted a case-control study nested in a three-arm randomized clinical pragmatic trial (ASCUS-COL trial) to evaluate the risk of CIN3+ associated with methylation levels according to serum folate concentrations. METHODS: Cases (n = 155) were women with histologically confirmed CIN2+ (113 CIN2, 38 CIN3, and 4 SCC) and controls were age and follow-up time at diagnosis-matched women with histologically confirmed ≤ CIN1 (n = 155), selected from the 1122 hrHPV + women of this trial. The concentrations of serum folate were determined by the radioimmunoassay SimulTRAC-SNB-VitaminB12/Folate-RIAKit and the methylation levels by the S5 classifier. Stepwise logistic regression models were used to estimate the association between folate or methylation levels and CIN2+ or CIN3+. The joint effect of folate levels and methylation on the risk of CIN3+ was estimated using combinations of categorical stratifications. RESULTS: Folate levels were significantly lower in women with CIN3+ than in other diagnostic groups (p = 0.019). The risk of CIN3+ was eight times higher (OR 8.9, 95% CI 3.4-24.9) in women with folate deficiency and high methylation levels than in women with normal folate and high methylation levels (OR 1.4, 95% CI 0.4-4.6). CONCLUSION: High methylation and deficient folate independently increased the risk of CIN3+ while deficient folate combined with high methylation was associated with a substantially elevated risk of CIN3+.
Asunto(s)
Células Escamosas Atípicas del Cuello del Útero , Deficiencia de Ácido Fólico , Displasia del Cuello del Útero , Femenino , Humanos , Estudios de Casos y Controles , Metilación de ADN , Ácido Fólico , Deficiencia de Ácido Fólico/genética , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/genética , Displasia del Cuello del Útero/patologíaRESUMEN
Objective: To evaluate the effectiveness of TruScreen (TS) for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with abnormal ThinPrep cytologic test (TCT) results. Methods: 466 women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) were enrolled and underwent TS, colposcopy and biopsy examination. Results: Compared with the high-risk human papillomavirus (hrHPV) test for CIN2+, significantly higher specificity of TS, combined TS and hrHPV (69.6 and 75.0 vs 36.8% in ASCUS; 59.0 and 69.9 vs 30.1% in LSIL), significantly higher positive predictive value of combined TS and hrHPV were observed (32.7 vs 24.6% in ASCUS; 47.9 vs 35.6% in LSIL). Conclusion: TS combined with hrHPV showed better performance in diagnosing CIN2+ in ASCUS/LSIL.
Asunto(s)
Células Escamosas Atípicas del Cuello del Útero , Infecciones por Papillomavirus , Lesiones Intraepiteliales Escamosas , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/patología , Frotis Vaginal , Sensibilidad y Especificidad , Displasia del Cuello del Útero/diagnóstico , Lesiones Intraepiteliales Escamosas/diagnóstico , Infecciones por Papillomavirus/diagnóstico , Papillomaviridae/genéticaRESUMEN
BACKGROUND: An Organised Cervical Cancer Screening Programme (OCCSP) was started in Poland in 2006/2007. Each woman aged 25 to 59 is eligible for a free Pap test every 3 years in OCCSP. Despite implementation of the OCCSP, the age-standardised cervical cancer (CC) incidence and mortality rates in 2019 were 7.3/100 000 and 3.9/100 000 respectively and were still higher than those in Western European countries with well-organised screening programmes. Apart from low coverage of the OCCSP, suboptimal performance of the screening test (conventional cytology) may be partially responsible for this situation. Several countries have already incorporated high risk Human Papillomavirus (hrHPV) testing in CC screening as a more sensitive tool reducing the risk of missing precancerous lesions and allowing for extension of screening intervals. The European Guidelines for Quality Assurance in Cervical Cancer Screening recommend pilot evaluation of a new screening test in country-specific conditions before its implementation. METHODS: The HIPPO project (HPV testing In Polish POpulation-based cervical cancer screening program) is a randomised health services study nested in the OCCSP in Poland. The project will randomise 33 000 women aged 30-59 years to cytology or hrHPV testing (ratio: 1:1) with age stratification. In the cytology arm women with repeated Atypical Squamous Cells of Undetermined Significance (ASC-US) or ≥ Low-Grade Squamous Intraepithelial Lesions (LSIL) are referred for colposcopy. In the other arm, hrHPV ( +) women with ≥ ASC-US reflex Liquid-Based Cytology (LBC) are referred for colposcopy. Primary endpoints include detection rates of histologically confirmed high grade intraepithelial lesions or worse (CIN2 +) in each arm. DISCUSSION: This pilot randomised healthcare study nested in the OCCSP in Poland will assess and compare the performance of hrHPV testing to current standard-cytology in order to make decisions on implementation of HPV-based screening in the country. TRIAL REGISTRATION: This randomised healthcare service study was prospectively registered at https://clinicaltrials.gov/ (identifier: NCT04111835, protocol ID 28/2019) on 19th of September 2019.
Asunto(s)
Células Escamosas Atípicas del Cuello del Útero , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Embarazo , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/epidemiología , Polonia/epidemiología , Detección Precoz del Cáncer/métodos , Tamizaje Masivo/métodos , Colposcopía , Política de Salud , Papillomaviridae , Frotis Vaginal/métodos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: To assess whether electrical impedance spectroscopy (EIS) as an adjunctive technology enhances the performance of colposcopy. DESIGN: Prospective cohort study. SETTING: University Hospital colposcopy clinic. PARTICIPANTS: Colposcopy with EIS for 647 women and conventional colposcopy for 962 women. INTERVENTIONS: Comparison of the performance of colposcopy by referral cervical cytology in two cohorts, with and without EIS as an adjunctive technology. OUTCOME MEASURES: Prevalence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), diagnostic testing accuracy to detect CIN2+ with and without EIS and their relative differences between cohorts. RESULTS: The prevalence of CIN2+ varied between the cohorts according to referral cytology: 17.0% after abnormal squamous cells of unknown significance referral cytology in EIS cohort and 9.1% in the reference cohort, 16.5% and 18.9% after low-grade squamous intraepithelial lesion (LSIL), 44.3% and 58.2% after atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (HSIL) (atypical squamous cells that cannot exclude HSIL), and 81.9% and 77.0% after HSIL cytology, respectively. Sensitivity to detect CIN2+ was higher in the EIS cohort, varying from 1.79 (95% CI 1.30 to 2.45) after LSIL referral cytology to 1.16 (95% CI 1.09 to 1.23) after HSIL referral cytology, with correspondingly lower specificity after any referral cytology. CONCLUSIONS: Colposcopy with EIS had overall higher sensitivity but lower specificity to detect CIN2+ than conventional colposcopy. CIN2+ prevalence rates were, however, not consistently higher in the EIS cohort, suggesting innate differences between the cohorts or truly lower detection rates of CIN2+ for EIS, highlighting the need for randomised controlled trials on the effectiveness of EIS.
Asunto(s)
Células Escamosas Atípicas del Cuello del Útero , Infecciones por Papillomavirus , Lesiones Intraepiteliales Escamosas , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Embarazo , Femenino , Humanos , Colposcopía , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Células Escamosas Atípicas del Cuello del Útero/patología , Espectroscopía Dieléctrica , Estudios Prospectivos , Displasia del Cuello del Útero/diagnóstico , Frotis Vaginal/métodos , Papillomaviridae , Infecciones por Papillomavirus/diagnósticoRESUMEN
OBJECTIVE: To compare the frequency of abnormal cervical cytological results with and without representation of the transformation zone (TZ) in a medium-sized city in Brazil according to the Bethesda categorization. METHODS: We performed an analytical observational study evaluating cytological results over 15 years from conventional smears collected within the Public Brazilian Health System in Araçatuba, Brazil. Tests were stratified by age and cytological result according to Brazilian guidelines and the Bethesda System. RESULTS: There were 261,881 examinations, 159,251 with and 102,630 without TZ representation. The global frequency of abnormal results was higher in smears with TZ representation (crude odds ratio [OR] 4.03; 95% confidence interval [CI] [3.71-4.38]). Considering only women between 25 and 64 years (the target of the national guidelines), there were higher results for high-grade squamous intraepithelial lesions (OR 11.54; 95% CI 6.74-19.78), low-grade squamous intraepithelial lesions (OR 2.82; 95% CI 2.17-3.67) atypical squamous cell in which high-grade intraepithelial lesion cannot be excluded (OR 6.90; 95% CI 4.91-9.66) and atypical squamous cell of undetermined significance (OR 3.53; 95% CI 3.11-4.01) among cases with TZ representation. CONCLUSION: Samples with TZ representation were associated with higher rates of abnormal results. Health professionals should be regularly trained to understand the weakness of cytological examinations when the TZ is not represented, especially in developing countries.
Asunto(s)
Células Escamosas Atípicas del Cuello del Útero , Humanos , Femenino , Brasil/epidemiología , Personal de Salud , Oportunidad Relativa , Salud PúblicaRESUMEN
OBJECTIVE: To investigate the infection status of high-risk human papillomavirus (HR-HPV) E6/E7 mRNA in patients with a cytological diagnosis of "atypical squamous cells of undetermined significance" (ASCUS) and to analyze the pathogenic rate of different high-risk HPV subtypes combined with biopsy pathological results to provide a more accurate basis for managing ASCUS patients. METHODS: A total of 1387 patients with ASCUS and HPV E6/E7 mRNA positivity who were referred for colposcopy were retrospectively analyzed. They were divided into HPV16+, 18/45 + and other HR-HPV + groups premenopausal and postmenopausal groups. The pathological results of the biopsy were divided into the LSIL- group (including normal and low-grade squamous intraepithelial lesions) and the HSIL + group (including high-grade squamous intraepithelial lesions and higher lesions). SPSS was used for the analysis. RESULTS: The age group 31-40 years had the highest level of HPV16+, and HPV18/45 + was the highest in the 41-50 years group. The detection rates of HSIL + in the HPV16+, HPV18/45+, HPV 16/18/45 + and Other HR-HPV + groups were 48.4%, 18.8%, 43.9% and 15.0%, respectively. The infection rates of HPV16/18/45 in postmenopausal and premenopausal women were 42.4% and 34.3%, respectively. In the HPV18/45 group, the incidence of HSIL + was 30.0% in postmenopausal women and 15.0% in premenopausal women (P < 0.01). In the HPV 16 + and Other HR-HPV + groups, the incidence of HSIL + in postmenopausal patients was not significantly different from that in premenopausal patients. The incidence of cervical cancer in postmenopausal patients is significantly higher than that in premenopausal patients. CONCLUSIONS: Colposcopy referral or further biopsy is recommended for all ASCUS patients with HPV16/18/45E6/E7 mRNA positivity and postmenopausal patients with HR-HPVE6/E7 mRNA positivity. For premenopausal ASCUS patients with other HR-HPV E6/E7 mRNA positivity, colposcopy should be performed if possible, depending on the specific situation, to achieve early detection and diagnosis.
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Células Escamosas Atípicas del Cuello del Útero , Infecciones por Papillomavirus , Humanos , Femenino , Adulto , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Infecciones por Papillomavirus/diagnóstico , Estudios Retrospectivos , Papillomaviridae , ARN MensajeroRESUMEN
INTRODUCTION: Cervical cancer precursor lesions occur due to persistent infection caused by human papillomavirus (HPV). One of the challenges of the Pap test is detecting lesions at a high risk of evolving into cancer. In this context, differentiating patients at low and high risk of developing cervical cancer becomes necessary. The Swede score, a standardized point system assigned based on colposcopy, is the most commonly used method to evaluate suspicious lesions. However, access to colposcopy is limited in low-income countries. It is, therefore, important to assess the applicability of less costly diagnostic methods in these situations to avoid a late diagnosis of cervical cancer. OBJECTIVE: To analyze histological outcomes of cytology tests with atypical squamous cells of undetermined significance (ASC-US and ASC-H) and to compare the performance of the Swede score with and without colposcopy. METHODS: The study was approved by the Ethics Committee via Plataforma Brasil (CAAE no. 41958320.6.0000.5259) and conducted by applying colposcopy score and naked eye score to patients with cytology alterations (ASC-US and ASC-H), with posterior analysis of cytological and histological results and comparison between the scores. RESULTS: A total of 34 women aged ranging from 24 to 65 years, with results of atypia with undetermined significance (ASC-US and ASC-H), were included in the study. The receiver operating characteristic curve was calculated for the naked eye inspection Swede score. The cut-off of 6 was considered to indicate the best sensitivity and specificity (55.56% and 93.75%, respectively). Then, the positive and negative predictive values were 90.91% and 65.22%, respectively. By increasing the cut-off to 7, specificity increased to 100%. For the colposcopic inspection, a cut-off of 6 indicates better specificity and positive predictive value (both 100%), whereas the negative predictive value was 57.14%. CONCLUSION: The correlation between the colposcopic and naked-eye Swede scores was statistically significant (0.82). Further studies with larger samples are important to establish the actual applicability of the naked eye method; however, in the absence of colposcopy, this appears to be an effective and very helpful method to make diagnostic decisions regarding HPV-induced lesions.
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Células Escamosas Atípicas del Cuello del Útero , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Virus del Papiloma Humano , BrasilRESUMEN
AIM: In Japan, primary human papilloma virus (HPV) testing has not been introduced for cervical cancer screening due to concerns that HPV-negative lesions may be missed and a lack of Japanese data. The purpose of this study was to evaluate the validity of primary HPV testing in Japan by analyzing cervical intraepithelial neoplasia 2 (CIN2) or more/high-risk HPV- (CIN2+/hrHPV-) cases in cervical cancer screening. METHODS: Data from 35 525 cervical cancer screenings with HPV testing and cervical cytology from 2011 to 2019 in Saga City, Japan, were reviewed. The cases with low-grade squamous intraepithelial lesion (LSIL+)/hrHPV- were analyzed in detail. RESULTS: The results of the 35 525 examinees were as follows: 31 123 were negative for intraepithelial lesion or malignancy (NILM)/hrHPV-, 2612 were NILM/hrHPV+, 262 were atypical squamous cells of undetermined significance (ASC-US)/hrHPV-, 213 were ASC-US/hrHPV+, 291 were LSIL+/hrHPV-, and 1024 were LSIL+/hrHPV+. Of the 256 LSIL+/hrHPV- examinees for whom histology was available, CIN2+ were CIN2 9.4% (24/256), CIN3 3.9% (10/256), cervical adenocarcinoma 0.4% (1/256), uterine corpus cancer 1.2% (3/256), and uterine sarcoma 0.4% (1/256). Overall, the rate of LSIL+/hrHPV- was 0.82% (291/35.525), 0.1% (36/35525) of which were cervical lesions with CIN2+. Only one cervical adenocarcinoma was detected, but gastric-type adenocarcinoma was not included. CONCLUSION: HPV-negative CIN2+ or cervical adenocarcinoma is not a concern for the introduction of primary HPV screening in Japan. Primary HPV testing in cervical cancer screening is considered a feasible method that can be used in Japan, although an algorithm suitable for Japan and a national-level management system need to be established.
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Adenocarcinoma , Células Escamosas Atípicas del Cuello del Útero , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/patología , Detección Precoz del Cáncer/métodos , Infecciones por Papillomavirus/patología , Japón/epidemiología , Displasia del Cuello del Útero/diagnóstico , Células Escamosas Atípicas del Cuello del Útero/patología , PapillomaviridaeRESUMEN
INTRODUCTION: Endometrial lesions are morphologically diverse and uncommon on cervical smears, with its detection rate and associated diagnostic categories uncharacterized. In this study, cervical smears matched to histologically proven endometrial hyperplasias and carcinomas were reviewed and compared with cervical in-situ-carcinomas/carcinomas, aiming to detail the diagnostic performance of cervical smears for upper tract and glandular lesions. METHODS: Pathology reports of cervical smears, hysterectomies, endometrial and cervical biopsies from 1995 to 2021 were retrieved. Diagnoses of cervical smears were matched to endometrial hyperplasias and carcinomas, or cervical carcinomas and reviewed. RESULTS: Totally 832 cervical smears (272 cervical carcinomas, 312 endometrial carcinomas, and 248 hyperplasias) were included. Considering all cytologic glandular diagnosis as positive, the detection rate of cervical adenocarcinoma-in-situ was the highest (64.3%), followed by cervical adenocarcinoma (63.8%), endometrial carcinoma (31.7%), and hyperplasia (with atypia-8.5%; without atypia-2.3%) (p < 0.001). Endometrial hyperplasia was most often diagnosed as atypical squamous cells of undetermined significance (ASCUS) (5.0%) or atypical glandular cells, not otherwise specified (3.6%) without indication of endometrial origin. For endometrial carcinomas, higher FIGO grading and endocervical involvement were associated with higher detection rates across all diagnostic categories (p = 0.002-0.028). High FIGO grade was associated with suspicious/favor neoplastic (C4) (31.1%vs10.3%, p < 0.001) and carcinoma (C5) (17.8% vs. 5.6%, p = 0.005) categories, but not for all glandular diagnoses combined (33.3% vs. 31.0%, p = 0.761). CONCLUSION: Detection rates for endometrial lesions are lower than cervical lesions but not insignificant. Endometrial hyperplasia should be recognized as a differential of human papilloma virus-negative ASCUS and prompt consideration of investigation of the upper genital tract.
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Adenocarcinoma , Células Escamosas Atípicas del Cuello del Útero , Carcinoma , Hiperplasia Endometrial , Neoplasias Endometriales , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Enfermedades Uterinas , Femenino , Humanos , Frotis Vaginal , Prueba de Papanicolaou , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/patología , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologíaRESUMEN
We conducted a prospective study to evaluate the prevalence of high-risk human papillomavirus (hr-HPV) positivity in women with atypical squamous cells of undetermined significance (ASC-US). Additionally, we assessed the association of hr-HPV positivity with the pathology of high-grade squamous intraepithelial lesions or worse (HSIL+) and the risk of subsequent detection of squamous intraepithelial lesions. A total of 376 women were included, with 242 (64.4%) exhibiting hr-HPV positivity. The predominant HPV genotypes were 16, 52 and 58. Factors associated with the immediate detection of HSIL+ pathology included a colposcopic impression of high-grade lesions, hr-HPV positivity, HPV 16 positivity, HPV 18 positivity, HPV 58 positivity, age less than 40 years, and biopsy of two or more pieces. However, only the first three factors were statistically significant in multivariate analysis. Among the 291 women who continued surveillance for 6 months or more, the median follow-up period was 41.8 months (interquartile range [IQR] 26.5-54.0). The prevalence of subsequent HSIL in women with hr-HPV positivity versus negativity was 3.6% versus 0.98%, respectively. The median time to the subsequent detection of SIL was 28.7 months (IQR 14.9-41.7). In conclusion, women with ASC-US in our study had a high proportion of hr-HPV positivity. Type-specific HPV testing could play a pivotal role in the development of specific management protocols for women with ASC-US.Clinical trial registration: https://thaiclinicaltrials.org , TCTR20161017002.
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Células Escamosas Atípicas del Cuello del Útero , Infecciones por Papillomavirus , Lesiones Intraepiteliales Escamosas , Neoplasias del Cuello Uterino , Femenino , Humanos , Adulto , Células Escamosas Atípicas del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Virus del Papiloma Humano , Genotipo , Estudios Prospectivos , Papillomaviridae/genética , Frotis Vaginal/métodosRESUMEN
BACKGROUND: Studies on the clinical performance of p16/Ki-67 dual-staining in detecting cervical lesions by menopausal status were limited. METHODS: 4364 eligible women were enrolled with valid p16/Ki-67, HR-HPV, and LBC test results, including 542 cancer and 217 CIN2/3 cases. The positivity rates of p16 and Ki-67 single staining and p16/ Ki-67 dual-staining were analyzed by different pathological grades and age groups. The sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV) of each test in different subgroups were calculated and compared. RESULTS: P16/Ki-67 dual-staining positivity increased with histopathological severity in premenopausal and postmenopausal women (P < 0.05), while no increasing trends of individual expression of p16 single staining and Ki-67 single staining were observed in postmenopausal women. P16/Ki-67 showed higher SPE (88.09% vs. 81.91%, P < 0.001) and PPV (33.8% vs. 13.18%, P < 0.001) in detecting CIN2/3, and higher SEN (89.97% vs. 82.61%, P = 0.012) and SPE (83.22% vs. 79.89%, P = 0.011) in detecting cancer in premenopausal women than postmenopausal women. For triaging the HR-HPV+ population to identify CIN2/3, p16/Ki-67 performed comparably to LBC in the premenopausal women, and showed higher PPV (51.14% vs. 23.08%, P < 0.001) in premenopausal than postmenopausal women. For triaging ASC-US/LSIL population, p16/Ki-67 demonstrated higher SPE and lower colposcopy referral rate than HR-HPV in both premenopausal and postmenopausal women. CONCLUSIONS: Expressions of p16/Ki-67 dual-staining between premenopausal and postmenopausal women are varied. P16/Ki-67 performs better in detecting cervical lesions in premenopausal women. For triaging, p16/Ki-67 is suitable for HR-HPV+ women, especially premenopausal women, to identify CIN2/3 and women with ASC-US/LSIL.
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Células Escamosas Atípicas del Cuello del Útero , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Femenino , Humanos , Células Escamosas Atípicas del Cuello del Útero/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Pueblos del Este de Asia , Antígeno Ki-67/metabolismo , Posmenopausia , Coloración y Etiquetado , Displasia del Cuello del Útero/patología , PremenopausiaRESUMEN
BACKGROUND: Optimizing the balance between colposcopy referrals and the detection of high-grade cervical intraepithelial neoplasia (CIN) during cervical cancer screening requires robust triage strategies. We evaluated the performance of extended HPV genotyping (xGT), in combination with cytology triage, and compared it to previously published performance data for high-grade CIN detection by HPV16/18 primary screening in combination with p16/Ki-67 dual staining (DS). METHODS AND MATERIALS: The baseline phase of the Onclarity trial enrolled 33,858 individuals, yielding 2978 HPV-positive participants. Risk values for ≥CIN3 were determined for Onclarity result groupings corresponding to HPV16, not HPV16 but HPV18 or 31, not HPV16/18/31 but HPV33/58 or 52, not HPV16/18/31/33/58/52 but HPV35/39/68 or 45 or 51 or 56/59/66 across all cytology categories. Published data from the IMPACT trial for HPV16/18 plus DS was utilized as a comparator during ROC analyses. RESULTS: There were 163 ≥ CIN3 cases detected. The ≥CIN3 risk stratum hierarchy (% risk of ≥CIN3) that resulted from this analysis included: >LSIL (39.4%); HPV16, ≤LSIL (13.3%); HPV18/31, ≤LSIL (5.9%); HPV33/58/52/45, ASC-US/LSIL (2.4%); HPV33/58/52, NILM (2.1%); HPV35/39/68/51/56/59/66, ASC-US/LSIL (0.9%); and HPV45/35/39/68/51/56/59/66, NILM (0.6%). For ≥CIN3 ROC analysis, the optimal cutoff for sensitivity versus specificity was approximated between not HPV16 but HPV18 or 31, any cytology (≥CIN3 sensitivity = 85.9% and colposcopy-to- ≥ CIN3 = 7.4) and not HPV16/18/31 but HPV33/58/52, NILM (≥CIN3 sensitivity = 94.5% and colposcopy-to- ≥CIN3 = 10.8). HPV16/18 with DS triage showed a sensitivity of 94.3%, with a colposcopy-to- ≥ CIN3 ratio of 11.4. CONCLUSIONS: xGT performed similarly compared to HPV primary screening plus DS for detection of high-grade CIN. xGT provides results that stratify risk in a flexible and reliable manner for colposcopy risk thresholds set by different guidelines or organizations.