RESUMEN
Despite widespread cervical cancer (CC) screening programs, low participation has led to high morbidity and mortality rates, especially in developing countries. Because early-stage CC often has no symptoms, a non-invasive and convenient diagnostic method is needed to improve disease detection. In this study, we developed a new approach for differentiating both CC and cervical intraepithelial neoplasia (CIN)2/3, a precancerous lesion, from healthy individuals by exploring CC fatty acid metabolic reprogramming. Analysis of public datasets suggested that various fatty acid metabolizing enzymes were expressed at higher levels in CC tissues than in normal tissues. Correspondingly, 11 free fatty acids (FFAs) showed significantly different serum levels in CC patient samples compared with healthy donor samples. Nine of these 11 FFAs also displayed significant alterations in CIN2/3 patients. We then generated diagnostic models using combinations of these FFAs, with the optimal model including stearic and dihomo-γ-linolenic acids. Receiver operating characteristic curve analyses suggested that this diagnostic model could detect CC and CIN2/3 more accurately than using serum squamous cell carcinoma antigen level. In addition, the diagnostic model using FFAs was able to detect patients regardless of clinical stage or histological type. Overall, the serum FFA diagnostic model developed in this study could be a powerful new tool for the non-invasive early detection of CC and CIN2/3.
Asunto(s)
Ácidos Esteáricos , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/sangre , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/diagnóstico , Ácidos Esteáricos/sangre , Adulto , Ácido 8,11,14-Eicosatrienoico/sangre , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Curva ROCRESUMEN
BACKGROUND: Value analysis of a small-molecule fluorescent probe for methylation detection in different cervical lesions. MATERIALS AND METHODS: (1) The grayscale values of distinct lesion tissues were remarkably distinct among the four groups (p < 0.05). The comparison of the grayscale value between the two groups showed that the CA group noticeably exceeded the LSIL and cervicitis groups, and the HSIL group was apparently higher than the LSIL and cervicitis groups (p < 0.05); (2) The mean grayscale values of the enrolled subjects were calculated with 55.21 as the midline, with >55.21 as positive and ≤55.21 as negative. RESULTS: The results showed that the positive rate of the cervicitis group was 0.00%, the LSIL group 67.74%, the HSIL group 83.33%, and the CA group 100.00%. The results among the four groups were notably distinct (p < 0.05); (3) The comparison among DAPI, probe, bright, and merged images of cervicitis, LSIL, HSIL, and CA indicated that different cervical lesions were with quite various stains. CONCLUSION: The grayscale value, positive rate, and stained picture of distinct cervical lesions were remarkably different. The small-molecule fluorescent probe has a good value in differentiating cervical lesions and can be considered for popularization and application.
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ADN (Citosina-5-)-Metiltransferasa 1 , Metilación de ADN , Colorantes Fluorescentes , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/genética , Adulto , Persona de Mediana Edad , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/genética , Anciano , Sensibilidad y Especificidad , Cervicitis Uterina/metabolismo , Displasia del Cuello del Útero/diagnósticoRESUMEN
Null.
Asunto(s)
Colposcopía , Conización , Genotipo , Prueba de Papanicolaou , Papillomaviridae , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Frotis Vaginal , Humanos , Femenino , Colposcopía/métodos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/patología , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/diagnóstico , Cuello del Útero/virología , Cuello del Útero/patología , CitologíaRESUMEN
OBJECTIVES: In this study, we aimed to validate the performance of the PAX1 and JAM3 methylation (PAX1m/JAM3m) test as a triage tool for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3 +) in non-16/18 high-risk human papillomavirus-positive patients (non-16/18 hrHPV +). METHODS: The triage performance of liquid-based cytology (LBC) and the PAX1m/JAM3m test for detecting CIN3 + were compared. RESULTS: In total, 1851 participants had cervical histological outcomes and were included in the analysis. The sensitivity/specificity of the LBC test results with atypical squamous cells of undetermined significance or worse (LBC ≥ ASCUS) and the PAX1m/JAM3m test were 90.1%/26.7% and 84.8%/88.5%, respectively. PAX1m/JAM3m( +) had the highest diagnostic AUC (0.866, 95% confidence interval (CI) 0.837-0.896) in the whole cohort. All cancers (n = 20) were detected by PAX1m/JAM3m(+). Compared with LBC ≥ ASCUS, PAX1m/JAM3m(+) reduced the number of patients who needed referral for colposcopy by 57.21% (74.66% vs. 17.45%). The odds ratios for detecting CIN3 + by LBC ≥ ASCUS and PAX1m/JAM3m(+) were 3.3 (95% CI 2.0-5.9) and 42.6 (27.1-69.6), respectively (p < 0.001). The combination of LBC ≥ ASCUS or PAX1m/JAM3m(+) slightly increased the diagnostic sensitivity (98.0%, 95% CI: 95.8-100%) and referral rate (77.09%) but reduced the diagnostic specificity (24.8%, 22.7-26.8%). CONCLUSIONS: In non-16/18 hrHPV(+) women, PAX1m/JAM3m was superior to cytology for detecting CIN3 + . Compared with LBC ≥ ASCUS, PAX1m/JAM3m(+) reduced the number of significant referrals to colposcopy without compromising diagnostic sensitivity.
Asunto(s)
Detección Precoz del Cáncer , Virus del Papiloma Humano , Factores de Transcripción Paired Box , Infecciones por Papillomavirus , Triaje , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , China , Metilación de ADN/genética , Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/estadística & datos numéricos , Virus del Papiloma Humano/aislamiento & purificación , Factores de Transcripción Paired Box/genética , Infecciones por Papillomavirus/diagnóstico , Estudios Prospectivos , Sensibilidad y Especificidad , Triaje/métodos , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virologíaRESUMEN
Objective: The objective of the study is to validate a new human papillomavirus (HPV) L1 high-risk specific serological assay in a case-control study. Methods: Serum samples of 138 patients (cervical intraepithelial neoplasia (CIN) 1, 2, and 3 and cervical cancer), 21 vaccinees, and 246 female controls were tested for the presence of HPV L1 high-risk specific antibodies. Results: HPV L1 high-risk antibodies were detected in 100% of the CIN1 and 2, 86.6% of the CIN3 and 82.4% of the cervical cancer cases, 100% of the vaccinees, and 3.9% of the female controls. Area under the curve (AUC) was calculated with 0.91 for controls versus CIN2+, 0.923 for controls versus CIN1+, and 0.968 for controls versus CIN1/2. Conclusion: The HPV L1 high-risk specific serological lateral flow rapid test shows promising data in the field of early detection of HPV high-risk induced cervical cancer and its precursor lesions. This easy-to-use, robust, and affordable approach could offer a chance to reach women in low- or middle-income countries (LMICs) that could not be reached by HPV molecular testing-based cervical cancer screening programs.
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Anticuerpos Antivirales , Detección Precoz del Cáncer , Infecciones por Papillomavirus , Sensibilidad y Especificidad , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/diagnóstico , Estudios de Casos y Controles , Adulto , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Anticuerpos Antivirales/sangre , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/diagnóstico , Persona de Mediana Edad , Detección Precoz del Cáncer/métodos , Proteínas Oncogénicas Virales/inmunología , Proteínas de la Cápside/inmunología , Adulto Joven , Papillomaviridae/inmunología , Papillomaviridae/aislamiento & purificación , AncianoRESUMEN
PURPOSE: Cervical cancer is the fourth most common cancer in women worldwide. A successful screening concept for cervical cancer reduces the incidence and mortality of cervical cancer. Quality indicators (QIs) derived from the screening guidelines for cervical cancer and used by the certified dysplasia units and dysplasia consultancies are evaluated in this paper. The aim of this paper is to present the current data from the annual reports of these units and consultancies. METHODS: The results of the basic data and indicators for the audit year 2022 in the gynaecological dysplasia consultancies and units are presented. In 2022, 84 dysplasia consultancies and 42 units were audited. 40 units and 84 consultancies are included in the annual report. QI outcomes for patients treated in certified dysplasia units and dysplasia consultancies are analysed. Median, overall proportion, and standard deviation were calculated for each QI. RESULTS: The indicator year 2021 was analysed, which was audited in 2022 and evaluated in 2023. A total of nine QIs were analysed. Most target goals were met by the 84 certified dysplasia consultancies and by the 40 dysplasia units. The QIs evaluated are implemented to a very high degree. The targets for the three QIs were achieved by both the dysplasia consultancies and the units in at least 95% of the certified centres (QI 1: 100%, QI 2: 95%, QI 3: 100%; QI 1: 100%, QI 2: 97%, QI 3: 100%, respectively). The presentation of patients to the tumour board by the consultancies/units is working; the units are attending the tumour board more regularly than in previous years. Where the target was not met, the auditors issued deviations or reduced the duration of the certificate. The cases are discussed intensively in the sense of an individual case analysis and with the determination of measures on-site. CONCLUSIONS: The targets for the various indicators were largely met by the dysplasia consultancies and units in the 2022 audit year. The certification of gynaecological dysplasia consultancies/units which have to cooperate with certified gynaecological cancer centres, has for the first time ensured the continuity of healthcare from prevention and early diagnosis to treatment of gynaecological cancers.
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Detección Precoz del Cáncer , Garantía de la Calidad de Atención de Salud , Indicadores de Calidad de la Atención de Salud , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Detección Precoz del Cáncer/normas , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/prevención & control , Derivación y ConsultaRESUMEN
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.
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Colposcopía , Legrado , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Adulto , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , Biopsia/métodos , Cuello del Útero/patología , Cuello del Útero/virología , Colposcopía/métodos , Legrado/métodos , Virus del Papiloma Humano/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Estudios Retrospectivos , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Frotis Vaginal/métodosRESUMEN
Cervical cancer is the fourth most common malignancy in women worldwide. The identification of human papillomavirus (HPV) as the main etiologic cause of cervical cancer has led to the development and adaptation of HPV molecular diagnostics as a cervical cancer screening and prevention tool. This article highlights six Food and Drug Administration-approved HPV molecular platforms, each with unique advantages and disadvantages. In addition, HPV vaccination and the emergence of HPV self-collection as an alternative testing strategy are discussed.
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Detección Precoz del Cáncer , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Humanos , Detección Precoz del Cáncer/métodos , Virus del Papiloma Humano/genética , Virus del Papiloma Humano/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Vacunas contra Papillomavirus/administración & dosificación , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/prevención & controlRESUMEN
BACKGROUND: Cervical cancer often originates from cervical cell dysplasia. Previous studies mainly focused on surgical margins and high-risk human papillomavirus persistence as factors predicting recurrence. New research highlights the significance of positive findings from endocervical curettage (ECC) during excision treatment. However, the combined influence of surgical margin and ECC status on dysplasia recurrence risk has not been investigated. METHODS: In this retrospective study, data from 404 women with high-grade squamous intraepithelial lesions (HSIL) who underwent large loop excision of the transformation zone (LLETZ) were analyzed. Records were obtained retrospectively from the hospital's patient database including information about histopathological finding from ECC, endocervical margin status with orientation of residual disease after LLETZ, recurrent/persistent dysplasia after surgical treatment and need for repeated surgery (LLETZ or hysterectomy). RESULTS: Patients with cranial (= endocervical) R1-resection together with cells of HSIL in the ECC experienced re-surgery 17 times. With statistical normal distribution, this would have been expected to happen 5 times (p < 0.001). The Fisher's exact test confirmed a statistically significant connection between the resection status together with the result of the ECC and the reoccurrence of dysplasia after surgery (p < 0,001). 40,6% of the patients with re-dysplasia after primary LLETZ had shown cranial R1-resection together with cells of HSIL in the ECC. Investigating the risk for a future abnormal Pap smear, patients with cranial R1-resection together with dysplastic cells in the ECC showed the greatest deviation of statistical normal distribution with SR = 2.6. CONCLUSION: Our results demonstrate that the future risk of re-dysplasia, re-surgery, and abnormal Pap smear for patients after LLETZ due to HSIL is highest within patients who were diagnosed with cranial (endocervical) R1-resection and with cells of HSIL in the ECC in their primary LLETZ. Consequently, the identification of patients, who could benefit of intensified observation or required intervention could be improved.
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Cuello del Útero , Legrado , Márgenes de Escisión , Recurrencia Local de Neoplasia , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Estudios Retrospectivos , Displasia del Cuello del Útero/cirugía , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/diagnóstico , Adulto , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/diagnóstico , Legrado/métodos , Cuello del Útero/cirugía , Cuello del Útero/patología , Persona de Mediana EdadRESUMEN
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.
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Colposcopía , Detección Precoz del Cáncer , Genotipo , Infecciones por Papillomavirus , Derivación y Consulta , Triaje , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/diagnóstico , Triaje/métodos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Detección Precoz del Cáncer/métodos , Adulto , Persona de Mediana Edad , Países Bajos/epidemiología , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/diagnósticoRESUMEN
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.
Asunto(s)
Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Estudios Retrospectivos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/complicaciones , China/epidemiología , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Adulto , Persona de Mediana Edad , Adulto Joven , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Colposcopía , Coinfección/virología , Coinfección/epidemiología , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomaviridae/clasificación , Anciano , Genotipo , IncidenciaRESUMEN
BACKGROUND: Nitric oxide (NO) may contribute to the persistence of high-risk human papillomavirus (hrHPV) infection, which has been linked to the development of premalignant lesions and cervical cancer. Our study aimed to examine the relationship between cervical NO metabolite (NOx) levels, hrHPV infection, and cytopathological findings. Additionally, we assessed cervical NOx levels as a biomarker for predicting hrHPV infection and epithelial atypia. METHODS: The study involved 74 women who attended the Gynecology and Obstetrics outpatient clinics at Cairo University Hospitals between November 2021 and August 2022. Cervical samples were subjected to Pap testing, assessment of NOx levels by the Griess method, and detection of hrHPV DNA by real-time polymerase chain reaction. RESULTS: High-risk HPV was detected in 37.8% of women. EA was found in 17.1% of cases, with a higher percentage among hrHPV-positive than negative cases (35.7% vs. 4.3%, p = 0.001). The most prevalent hrHPV genotype was HPV 16 (89.3%). The cervical NOx level in hrHPV-positive cases was significantly higher (37.4 µmol/mL, IQR: 34.5-45.8) compared to negative cases (2.3 µmol/mL, IQR: 1.2-9.8) (p = < 0.001). Patients with high-grade atypia showed significantly higher NOx levels (38.0 µmol/mL, IQR: 24.6-94.7) in comparison to NILM and low-grade atypia cases (5.0 µmol/mL, IQR: 1.6-33.3 and 34.5 µmol/mL, IQR: 11.7-61.7, respectively) (p = 0.006). Although the NOx levels among hrHPV-positive cases with low-grade atypia (40.4 µmol/mL, IQR: 33.3â61.8) were higher than those with NILM (36.2 µmol/mL, IQR: 35.7â44.0) and high-grade atypia (38.0 µmol/mL, IQR: 24.6â94.7), the difference was not significant (p = 0.771). ROC curve analysis indicated that the cervical NOx cut-off values of > 23.61 µmol/mL and > 11.35 µmol/mL exhibited good diagnostic accuracy for the prediction of hrHPV infection and EA, respectively. CONCLUSIONS: The high prevalence of hrHPV infection, particularly HPV 16, in our hospital warrants targeted treatment and comprehensive screening. Elevated cervical NOx levels are associated with hrHPV infection and high-grade atypia, suggesting their potential use as biomarkers for predicting the presence of hrHPV and abnormal cytological changes.
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Cuello del Útero , Óxido Nítrico , Infecciones por Papillomavirus , Humanos , Femenino , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Adulto , Cuello del Útero/virología , Cuello del Útero/patología , Persona de Mediana Edad , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/diagnóstico , Adulto Joven , ADN Viral/genética , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/diagnóstico , Biomarcadores/análisis , Genotipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Frotis Vaginal , Prueba de Papanicolaou , CitologíaAsunto(s)
Inhibidor p16 de la Quinasa Dependiente de Ciclina , Antígeno Ki-67 , Neoplasias del Cuello Uterino , Femenino , Humanos , Cuello del Útero/patología , Cuello del Útero/metabolismo , Consenso , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Detección Precoz del Cáncer/métodos , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/virología , Coloración y Etiquetado/métodos , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/metabolismo , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Frotis VaginalRESUMEN
Cervical cancer screening has reduced morbidity and mortality in many countries, but efforts to optimize screening modalities and schedules are ongoing. Using data from a randomized trial conducted in British Columbia, Canada, in conjunction with a provincial screening registry, Gottschlich and colleagues demonstrated that the estimated risk for precancerous disease (cervical intraepithelial neoplasia grades 2 or worse) at 8 years following a negative human papillomavirus (HPV) test was similar to the current standard of care (Pap testing after 3 years). The study supports extending screening intervals for those with a negative HPV test beyond currently recommended 5-year intervals. In an ideal world, the resources saved through less frequent routine cervical screening could be redirected to increasing screening uptake and follow-up of abnormalities to improve equity in cervical cancer prevention. However, implementation of extending screening intervals remains less than straightforward in settings with fragmented healthcare systems that lack information systems to support patient call/recall, such as the United States. To achieve the full promise of primary HPV testing, stakeholders at every level must commit to identifying and addressing the diverse spectrum of barriers that undergird existing inequities in care access, appropriately resource implementation strategies, and improve health information systems. See related article by Gottschlich et al., p. 904.
Asunto(s)
Detección Precoz del Cáncer , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/epidemiología , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/epidemiología , Detección Precoz del Cáncer/métodos , Papillomaviridae/aislamiento & purificación , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/prevención & control , Displasia del Cuello del Útero/epidemiología , Tamizaje Masivo/métodos , Colombia Británica/epidemiologíaRESUMEN
INTRODUCTION: Low-cost, accurate high-risk HPV tests are needed for cervical cancer screening in limited-resource settings. OBJECTIVE: To compare the performance of the low-cost Hybribio-H13 test with the Hybrid Capture® 2 to detect cervical intraepithelial neoplasia grade 2 or 3 (CIN2 and CIN3). MATERIALS AND METHODS: Archived baseline samples tested by the Hybrid Capture® 2 from women of the ASCUS-COL trial, aged 20 to 69 years, with biopsy-colposcopy directed diagnosis of CIN2+ (n = 143), CIN3+ (n = 51), and < CIN2 (n = 632) were blindly tested by the Hybribio-H13 test. RESULTS: The relative sensitivity of the Hybribio-H13 test versus the Hybrid Capture® 2 for detecting CIN2+ was 0.89 (90% CI = 0,80-0,98; NIT = 0,66), and for CIN3+ was 0,92 (90% CI = 0,85-0,98; NIT = 0,35). Relative specificity was 1.19 (90% CI = 1.05-1.33; NIT <0.00001). In the analysis restricted to women older than 30 years, the relative sensitivity of the Hybribio-H13 for CIN3+ was marginally below unity (ratio = 0.97; 90% CI = 0.95-0.99), and the specificity remained higher than the Hybrid Capture® 2 test. CONCLUSION: The Hybribio-H13 test was as specific as the Hybrid Capture® 2 for detecting CIN2+ or CIN3+ but less sensitive. Considering these results and the young age of the population recruited for screening because of ASCUS cytology, we suggest our results warrant the evaluation of the Hybribio-H13 for screening cervical cancer, especially in the evaluated population.
Introducción. Se necesitan pruebas para detectar genotipos de VPH de alto riesgo, precisas y de bajo costo, para la tamización del cáncer de cuello uterino en entornos de recursos limitados. Objetivo. Comparar el desempeño de la prueba de bajo costo Hybrid-H13 con la de Hybrid Capture® 2 para detectar NIC2+ y NIC3+. Materiales y métodos. Se analizaron en ciego muestras de la línea base provenientes de mujeres del estudio ASCUS-COL, entre los 20 y los 69 años, con diagnóstico dirigido por biopsia-colposcopia de NIC2+ (n = 143), NIC3 + (n = 51) y < NIC2 (n = 632) con la prueba para detección de virus de papiloma humano Hybribio-H13. Estas muestras fueron previamente evaluadas con la prueba Hybrid Capture® 2. Resultados. La sensibilidad relativa de Hybribio-13 versus la de Hybrid Capture® 2 para detectar NIC2+ fue de 0,89 (IC90%: 0,80-0,98; NIT = 0,66) y para NIC3+ fue de 0,92 (IC90%: 0,85-0,98; NIT = 0,35). La especificidad relativa fue de 1,19 (IC90%: 1,05-1,33; NIT <0,00001). En el análisis restringido a mujeres mayores de 30 años, la sensibilidad relativa de Hybribio-H13 para NIC3+ estuvo marginalmente por debajo de la unidad (proporción = 0,97; IC90%: 0,95-0,99) y la especificidad permaneció más alta que la de la prueba Hybrid Capture® 2. Conclusión. La prueba de Hybribio-H13 fue tan específica como la de Hybrid Capture® 2, pero menos sensible para detectar NIC2+ o NIC3+. Teniendo en cuenta estos resultados y la temprana edad de la población reclutada en la tamización por la presencia de ASCUS en la citología, se sugiere continuar con la evaluación de la prueba Hybribio-H13 para la detección de cáncer de cuello uterino en poblaciones con las mismas características que las de la aquí evaluada.
Asunto(s)
Infecciones por Papillomavirus , Sensibilidad y Especificidad , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virología , Persona de Mediana Edad , Adulto , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Anciano , Infecciones por Papillomavirus/diagnóstico , Adulto Joven , Detección Precoz del Cáncer/métodos , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Virus del Papiloma HumanoRESUMEN
Cervical cancer (CC) remains a major health concern globally, much of the brunt of which is experienced by the low- and middle-income countries where screening in terms of cytology and DNA genotyping for the high-risk oncogenic subtypes of the human papilloma virus (hr-HPV) is either inadequate or performed rather late. In this study, we aimed to determine biomarkers or panels of biomarkers that are capable of diagnosing the precancerous cervical intraepithelial neoplasia (CIN) stages from healthy and CC patients via untargeted gas chromatography-mass spectrometry-based metabolomics. Various cross-comparisons were conducted from which differential metabolites were identified. The underlying metabolic pathways based on the differential metabolites identified from the various cross-comparisons mainly related to amino acids biosynthesis and metabolism and steroid hormone biosynthesis. From all cross-comparisons, two common metabolites namely, 2-methyl-1-propylamine (also known as isobutylamine) and estrone were found to possess excellent to good diagnostic abilities, especially in distinguishing the early stages of CIN (CIN I, CIN II) from healthy women and CC patients. These findings have clinical significance in the sense that, once validated the 2-biomarker panel could be adopted in clinical practice for early diagnosis of CIN and invasive carcinoma. This would therefore inform the choice of treatment to be initiated by the clinician.
Asunto(s)
Biomarcadores de Tumor , Cromatografía de Gases y Espectrometría de Masas , Metabolómica , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/sangre , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/sangre , Cromatografía de Gases y Espectrometría de Masas/métodos , Metabolómica/métodos , Adulto , Biomarcadores de Tumor/sangre , Persona de Mediana Edad , Estrona/sangre , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/sangre , Estadificación de NeoplasiasRESUMEN
Antenatal cervical screening aims to detect cervical intraepithelial neoplasms as precancerous lesions and invasive cervical cancer. Whether this screening is performed routinely during pregnancy varies depending on each country's screening participation rates, guidelines, and the risks to the pregnant woman. In some countries with the high rate of routinely implemented cervical screening among the target women, women are recommended to defer cervical screening intentionally to post-delivery, though having screening in consultation with physicians may be possible if routine screening overlaps. However, when cervical screening rate in fertile women is low and the incidence of cervical cancer is high, cervical screening during pregnancy may play an important role in the early detection of cervical cancer. Cervical screening using high-risk human papillomavirus (HPV) testing is accepted worldwide as a highly sensitive and objective test method, and it should replace traditional primary cervical cytology in the future. However, the benefits and disadvantages of using HPV testing in pregnant women is unclear because a false positive rate may be increased due to pregnant women being generally under an immunosuppressed condition.
Asunto(s)
Detección Precoz del Cáncer , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/prevención & control , Infecciones por Papillomavirus/diagnóstico , Embarazo , Detección Precoz del Cáncer/métodos , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virología , Tamizaje Masivo/métodos , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Neoplásicas del Embarazo/diagnóstico , Frotis VaginalRESUMEN
BACKGROUND: In China, the national cervical cancer screening protocol involves initial testing for high-risk human papillomavirus (hrHPV), followed by cytology for hrHPV-positive cases. This study evaluates the effectiveness of PAX1 methylation (PAX1m) analysis in identifying precancerous or cancerous lesions in cervical samples from Chinese women positive for non-16/18 hrHPV strains. METHODS: Between February 2022 and March 2023, 281 cervical samples from non-16/18 hrHPV-positive women underwent cytological examination and PAX1m analysis. The study assessed the statistical relationship between PAX1m levels and the presence of cervical lesions, comparing the diagnostic performance of PAX1m to conventional cytology. RESULTS: A significant association was found between PAX1 methylation levels and the risk of CIN2 + and CIN3 + lesions, with 47 instances of CIN2 + detected. Odds ratios (ORs) for moderate and high PAX1m levels were 8.86 (95% CI: 2.24-42.17) and 166.32 (95% CI: 47.09-784.97), respectively. The area under the ROC curve for PAX1m in identifying CIN2 + lesions was 0.948 (95% CI: 0.895-0.99). PAX1m demonstrated similar sensitivity and negative predictive value (NPV) to cytology but reduced the colposcopy referral rate from 47.7% with cytology alone to 25.6% with PAX1m, showing superior specificity and positive predictive value across age groups. CONCLUSIONS: PAX1 methylation is a strong indicator of CIN2 + and CIN3 + risk, offering diagnostic performance comparable to cytology with the added benefit of reduced unnecessary colposcopy referrals. These findings support the use of PAX1m analysis as a reliable tool for triaging non-16/18 hrHPV-positive women in outpatient settings.
Asunto(s)
Metilación de ADN , Detección Precoz del Cáncer , Factores de Transcripción Paired Box , Infecciones por Papillomavirus , Triaje , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/genética , Persona de Mediana Edad , Detección Precoz del Cáncer/métodos , Adulto , Factores de Transcripción Paired Box/genética , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Triaje/métodos , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/genética , China/epidemiología , Anciano , Curva ROC , Biomarcadores de Tumor/genética , Frotis VaginalRESUMEN
INTRODUCTION: In Denmark, where human papillomavirus (HPV) -based cervical cancer screening is being implemented, the aim of this pilot implementation study was to test a specific screening algorithm, assess follow-up examination attendance, and measure the proportion of precancer lesions found in relation to the number of women referred for colposcopy. MATERIAL AND METHODS: From May 2017 to December 2020, 36 417 women in the uptake area of the Department of Pathology, Vejle Hospital, Region of Southern Denmark, were included in the HPV group. Women positive for HPV16/18 irrespective of cytology and women positive for other high-risk HPV (hrHPV) types having concomitant abnormal cytology were referred directly to colposcopy. Women positive for other hrHPV types and normal cytology were referred to repeat screening after 12 months, and hrHPV negative to routine screening after three years. We obtained information on screening results and subsequent histological diagnosis from the Danish Pathology Databank through September 2022. RESULTS: 3.6% of the women were referred to colposcopy after primary screening, 5% to repeat screening after 12 months, and 91.4% back to routine screening. High follow-up rates were observed: 96% attended colposcopy after primary screening, with 91% attending colposcopy after repeat screening. CIN3+ was detected at colposcopy following the primary screening in 28.1% of HPV16/18-positive women and 18.2% of those positive for other hrHPV types with concomitant abnormal cytology. Of the women with other hrHPV and simultaneous ASCUS/LSIL, 8% had CIN3+. At the repeat screening, 43% had become hrHPV negative, 55% were persistently positive for other hrHPV, and 2% had turned positive for HPV16/18. At the colposcopy following repeat screening, 10.1% of the women positive for other hrHPV were diagnosed with CIN3+, in comparison with 11.1% of the HPV16/18-positive women. CONCLUSIONS: In this pilot implementation study, an algorithm for HPV-based screening was evaluated in a Danish setting. The results demonstrated high attendance at follow-up examinations and provided insights into the number of colposcopy referrals and the detection of CIN2 and CIN3+ cases. The results suggest that women testing positive for other hrHPV in combination with ASCUS/LSIL at primary screening could potentially be referred to repeat screening instead of an immediate colposcopy.