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1.
CA Cancer J Clin ; 70(5): 321-346, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32729638

RESUMEN

The American Cancer Society (ACS) recommends that individuals with a cervix initiate cervical cancer screening at age 25 years and undergo primary human papillomavirus (HPV) testing every 5 years through age 65 years (preferred); if primary HPV testing is not available, then individuals aged 25 to 65 years should be screened with cotesting (HPV testing in combination with cytology) every 5 years or cytology alone every 3 years (acceptable) (strong recommendation). The ACS recommends that individuals aged >65 years who have no history of cervical intraepithelial neoplasia grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening (qualified recommendation). These new screening recommendations differ in 4 important respects compared with the 2012 recommendations: 1) The preferred screening strategy is primary HPV testing every 5 years, with cotesting and cytology alone acceptable where access to US Food and Drug Administration-approved primary HPV testing is not yet available; 2) the recommended age to start screening is 25 years rather than 21 years; 3) primary HPV testing, as well as cotesting or cytology alone when primary testing is not available, is recommended starting at age 25 years rather than age 30 years; and 4) the guideline is transitional, ie, options for screening with cotesting or cytology alone are provided but should be phased out once full access to primary HPV testing for cervical cancer screening is available without barriers. Evidence related to other relevant issues was reviewed, and no changes were made to recommendations for screening intervals, age or criteria for screening cessation, screening based on vaccination status, or screening after hysterectomy. Follow-up for individuals who screen positive for HPV and/or cytology should be in accordance with the 2019 American Society for Colposcopy and Cervical Pathology risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors.


Asunto(s)
Detección Precoz del Cáncer/normas , Tamizaje Masivo/normas , Papillomaviridae/aislamiento & purificación , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Anciano , American Cancer Society , Femenino , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Vacunas contra Papillomavirus , Estados Unidos , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Frotis Vaginal , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/prevención & control , Displasia del Cuello del Útero/virología
2.
Int J Cancer ; 155(5): 905-915, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38648390

RESUMEN

Japan is lagging in cervical cancer prevention. The effectiveness of a self-sampling human papillomavirus (HPV) test, a possible measure to overcome this situation, has not yet been evaluated. A randomized controlled trial was performed to evaluate the effectiveness of a self-sampling HPV test on detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and screening uptake. Women between 30 and 58 years old who did not participate in the cervical cancer screening program for ≥3 years were eligible and assigned to the intervention group (cytology or self-sampling HPV test) or control group (cytology). Participants assigned to the intervention group were sent a self-sampling kit according to their ordering (opt-in strategy). A total of 7337 and 7772 women were assigned to the intervention and control groups, respectively. Screening uptake in the intervention group was significantly higher than that in the control group (20.0% vs. 6.4%; risk ratio: 3.10; 95% confidence interval [CI]: 2.82, 3.42). The compliance rate with cytology triage for HPV-positive women was 46.8% (95% CI: 35.5%, 58.4%). CIN2+ was detected in five and four participants in the intervention and control groups, respectively; there was no difference for intention-to-screen analysis (risk ratio: 1.32; 95% CI: 0.36, 4.93). Self-sampling of HPV test increased screening uptake; however, no difference was observed in the detection of CIN2+, probably due to the low compliance rate for cytology triage in HPV-positive women. Efforts to increase cytology triage are essential to maximize precancer detections.


Asunto(s)
Detección Precoz del Cáncer , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Persona de Mediana Edad , Adulto , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/epidemiología , Japón/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Detección Precoz del Cáncer/métodos , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/epidemiología , Papillomaviridae/aislamiento & purificación , Frotis Vaginal/métodos , Manejo de Especímenes/métodos , Tamizaje Masivo/métodos , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/virología , Virus del Papiloma Humano
3.
Int J Cancer ; 155(5): 816-827, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38602045

RESUMEN

Overexpression of HPV-oncoproteins E6 and E7 is necessary for HPV-driven cervical carcinogenesis. Hence, these oncoproteins are promising disease-specific biomarkers. We assessed the technical and operational characteristics of the 8-HPV-type OncoE6/E7 Cervical Test in different laboratories using cervical samples from HPV-positive women living with (WLWH) and without HIV. The 8-HPV-type OncoE6/E7 Test (for short: "OncoE6/E7 test") was performed in 2833 HIV-negative women and 241 WLWH attending multicentric studies in Latin America (ESTAMPA study), and in Africa (CESTA study). Oncoprotein positivity were evaluated at each testing site, according to HIV status as well as type-specific agreement with HPV-DNA results. A feedback questionnaire was given to the operators performing the oncoprotein test to evaluate their impression and acceptability regarding the test. The OncoE6/E7 test revealed a high positivity rate heterogeneity across all testing sites (I2: 95.8%, p < .01) with significant lower positivity in WLWH compared to HIV-negative women (12% vs 25%, p < .01). A similar HPV-type distribution was found between HPV DNA genotyping and oncoprotein testing except for HPV31 and 33 (moderate agreement, k = 0.57). Twenty-one laboratory technicians were trained on oncoprotein testing. Despite operators' concerns about the time-consuming procedure and perceived need for moderate laboratory experience, they reported the OncoE6/E7 test as easy to perform and user-friendly for deployment in resource-limited settings. The high positivity rate variability found across studies and subjectivity in test outcome interpretation could potentially results in oncoprotein false positive/negative, and thus the need for further refinements before implementation of the oncoprotein testing in screen-triage-and-treat approaches is warranted.


Asunto(s)
Detección Precoz del Cáncer , Infecciones por VIH , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/diagnóstico , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/complicaciones , Detección Precoz del Cáncer/métodos , Infecciones por VIH/virología , Infecciones por VIH/diagnóstico , Infecciones por VIH/complicaciones , Infecciones por VIH/metabolismo , Adulto , Persona de Mediana Edad , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/metabolismo , Países en Desarrollo , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , América Latina/epidemiología , ADN Viral/análisis , ADN Viral/genética , África/epidemiología
4.
Int J Cancer ; 155(1): 61-70, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38418719

RESUMEN

High-risk human papillomavirus (hrHPV) is the cause of virtually all cervical cancers, most vaginal and anal cancers, and some vulvar cancer cases. With HPV testing becoming the primary screening method for cervical cancer, understanding the link between cervical hrHPV infection and the risk of other anogenital cancers is crucial. We assessed the risk of vulvar, vaginal and anal cancer and precancer (VIN2+, VaIN2+ and AIN2+) in a prospective cohort study including 455,349 women who underwent cervical hrHPV testing in Denmark from 2005 to 2020. We employed Cox proportional hazard models, adjusting for age, calendar year and HPV vaccination status, and estimated hazard ratios (HRs) and 95% confidence intervals (CI). We used the Aalen Johansen estimator to calculate the absolute risks of VIN2+, VaIN2+ and AIN2+. In total, 15% of the women were hrHPV positive at baseline. A positive cervical hrHPV test was associated with increased incidence of vulvar, vaginal and anal squamous cell carcinoma (SCC). Five-year risk estimates of VIN2+, VaIN2+ and AIN2+ among hrHPV-positive women (0.45%, 0.14% and 0.12%) were higher than among hrHPV-negative women (0.14%, 0.01% and 0.05%). Particularly high risk was observed among the hrHPV-positive women of the oldest age, with a history of anogenital precancer and those not HPV vaccinated. In conclusion, our study confirms the association between cervical hrHPV infection and non-cervical anogenital precancers and cancers. Currently, no established risk threshold or guidelines for follow-up. As HPV testing becomes the primary method for cervical cancer screening, future data will help define high-risk groups and acceptable risk thresholds.


Asunto(s)
Neoplasias del Ano , Infecciones por Papillomavirus , Lesiones Precancerosas , Neoplasias Vaginales , Neoplasias de la Vulva , Humanos , Femenino , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/complicaciones , Neoplasias del Ano/virología , Neoplasias del Ano/epidemiología , Neoplasias de la Vulva/virología , Neoplasias de la Vulva/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Adulto , Lesiones Precancerosas/virología , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/patología , Neoplasias Vaginales/virología , Neoplasias Vaginales/epidemiología , Neoplasias Vaginales/patología , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Dinamarca/epidemiología , Anciano , Incidencia , Carcinoma de Células Escamosas/virología , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Papillomaviridae/aislamiento & purificación , Detección Precoz del Cáncer , Factores de Riesgo , Citología
5.
Cancer Causes Control ; 35(6): 935-942, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38368574

RESUMEN

BACKGROUND: High-risk human papillomavirus (hrHPV) detection in self-collected urine samples (SeCUS) may be a promising alternative for cervical cancer screening because of its greater acceptability, as long as it can offer comparable sensitivity to clinician-collected cervical samples (CCoS) for detecting precancer lesions. OBJECTIVE: To evaluate the performance of the SeCUS compared to that of the CCoS for cervical intraepithelial neoplasia grade 3 (CIN3) detection among hrHPV-positive women receiving colposcopy in Mexico City using different specific extended HPV typing procedures: HPV16/18, HPV16/18/35/39/68 or HPV16/18/35/39/68/31. METHODS: From March 2017 to August 2018, 4,158 female users of the cervical cancer screening program at Tlalpan Sanitary Jurisdiction in Mexico City were invited to participate in the FRIDA-Tlalpan study. All participants provided ≥ 30 mL of SeCUS, and then a CCoS was obtained with Cervex-Brush®, which was used for hrHPV typing. Participants who tested positive for hrHPV in CCoS were referred for colposcopy for diagnostic confirmation, and all SeCUS of these women were also tested for hrHPV typing. RESULTS: In total, 561 hrHPV-positive women were identified by CCoS via colposcopy, and 82.2% of the SeCUS of these women were also hrHPV positive. From both CCoS and SeCUS, 7 cases of CIN3 were detected. Considering HPV16/18 typing, CCoS and SeCUS detected 4 cases of CIN3, but after HPV16/18/35/39/68/31 extension typing, both CCoS and SeCUS detected all 7 of the CIN3 cases among the hrHPV-positive women. CONCLUSIONS: Using extended hrHPV typing based on HPV16/18/35/39/68/31, our results suggest that the performance of SeCUS may be equivalent to that of CCoS for detecting CIN3 lesions. Although our results are inconclusive, they support the hypothesis that SeCUS may be an attractive alternative worthy of further research.


Asunto(s)
Colposcopía , Detección Precoz del Cáncer , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/orina , México/epidemiología , Adulto , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/orina , Persona de Mediana Edad , Detección Precoz del Cáncer/métodos , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/orina , Displasia del Cuello del Útero/epidemiología , Lesiones Precancerosas/virología , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/orina , Papillomaviridae/aislamiento & purificación , Papillomaviridae/genética
6.
J Transl Med ; 22(1): 396, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38685022

RESUMEN

BACKGROUND: The aim of this study was to assess the microbial variations and biomarkers in the vaginal and oral environments of patients with human papillomavirus (HPV) and cervical cancer (CC) and to develop novel prediction models. MATERIALS AND METHODS: This study included 164 samples collected from both the vaginal tract and oral subgingival plaque of 82 women. The participants were divided into four distinct groups based on their vaginal and oral samples: the control group (Z/KZ, n = 22), abortion group (AB/KAB, n = 17), HPV-infected group (HP/KHP, n = 21), and cervical cancer group (CC/KCC, n = 22). Microbiota analysis was conducted using full-length 16S rDNA gene sequencing with the PacBio platform. RESULTS: The vaginal bacterial community in the Z and AB groups exhibited a relatively simple structure predominantly dominated by Lactobacillus. However, CC group shows high abundances of anaerobic bacteria and alpha diversity. Biomarkers such as Bacteroides, Mycoplasma, Bacillus, Dialister, Porphyromonas, Anaerococcus, and Prevotella were identified as indicators of CC. Correlations were established between elevated blood C-reactive protein (CRP) levels and local/systemic inflammation, pregnancy, childbirth, and abortion, which contribute to unevenness in the vaginal microenvironment. The altered microbial diversity in the CC group was confirmed by amino acid metabolism. Oral microbial diversity exhibited an inverse pattern to that of the vaginal microbiome, indicating a unique relationship. The microbial diversity of the KCC group was significantly lower than that of the KZ group, indicating a link between oral health and cancer development. Several microbes, including Fusobacterium, Campylobacter, Capnocytophaga, Veillonella, Streptococcus, Lachnoanaerobaculum, Propionibacterium, Prevotella, Lactobacillus, and Neisseria, were identified as CC biomarkers. Moreover, periodontal pathogens were associated with blood CRP levels and oral hygiene conditions. Elevated oral microbial amino acid metabolism in the CC group was closely linked to the presence of pathogens. Positive correlations indicated a synergistic relationship between vaginal and oral bacteria. CONCLUSION: HPV infection and CC impact both the vaginal and oral microenvironments, affecting systemic metabolism and the synergy between bacteria. This suggests that the use of oral flora markers is a potential screening tool for the diagnosis of CC.


Asunto(s)
Microbiota , Boca , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Vagina , Humanos , Femenino , Vagina/microbiología , Vagina/virología , Neoplasias del Cuello Uterino/microbiología , Neoplasias del Cuello Uterino/virología , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/microbiología , Boca/microbiología , Boca/virología , Adulto , Persona de Mediana Edad , Papillomaviridae/aislamiento & purificación , Papillomaviridae/genética , ARN Ribosómico 16S/genética , Virus del Papiloma Humano
7.
J Med Virol ; 96(6): e29741, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38922964

RESUMEN

Cervical cancer is the fourth most common cancer in women worldwide and is caused by persistent infection with high-risk types of human papillomavirus (HPV). HPV viral load, the amount of HPV DNA in a sample, has been suggested to correlate with cervical disease severity, and with clinical outcome of cervical cancer. In this systematic review, we searched three databases (EMBASE, PubMed, Web of Science) to examine the current evidence on the association between HPV viral load in cervical samples and disease severity, as well as clinical outcome. After exclusion of articles not on HPV, cervical cancer, or containing clinical outcomes, 85 original studies involving 173 746 women were included. The vast majority (73/85 = 85.9%) reported that a higher viral load was correlated with higher disease severity or worse clinical outcome. Several studies reported either no correlation (3/85 = 3.5%), or the opposite correlation (9/85 = 10.6%); possible reasons being different categorization of HPV viral load levels, or the use of specific sampling methods. Despite variations in study design and populations, the above findings suggest that HPV viral load is correlated to clinical outcome, and may become an important biomarker for treatment selection and response monitoring for cervical cancer.


Asunto(s)
Papillomaviridae , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Carga Viral , Humanos , Femenino , Infecciones por Papillomavirus/virología , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomaviridae/clasificación , Neoplasias del Cuello Uterino/virología , Índice de Severidad de la Enfermedad , ADN Viral , Enfermedades del Cuello del Útero/virología , Virus del Papiloma Humano
8.
J Med Virol ; 96(5): e29652, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38727029

RESUMEN

Human papillomavirus (HPV) genotyping is widely used, particularly in combination with high-risk (HR) HPV tests for cervical cancer screening. We developed a genotyping method using sequences of approximately 800 bp in the E6/E7 region obtained by PacBio single molecule real-time sequencing (SMRT) and evaluated its performance against MY09-11 L1 sequencing and after the APTIMA HPV genotyping assay. The levels of concordance of PacBio E6/E7 SMRT sequencing with MY09-11 L1 sequencing and APTIMA HPV genotyping were 100% and 90.8%, respectively. The sensitivity of PacBio E6/EA7 SMRT was slightly greater than that of L1 sequencing and, as expected, lower than that of HR-HPV tests. In the context of cervical cancer screening, PacBio E6/E7 SMRT is then best used after a positive HPV test. PacBio E6/E7 SMRT genotyping is an attractive alternative for HR and LR-HPV genotyping of clinical samples. PacBio SMRT sequencing provides unbiased genotyping and can detect multiple HPV infections and haplotypes within a genotype.


Asunto(s)
Genotipo , Técnicas de Genotipaje , Papillomaviridae , Infecciones por Papillomavirus , Humanos , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/diagnóstico , Femenino , Técnicas de Genotipaje/métodos , Papillomaviridae/genética , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/diagnóstico , Análisis de Secuencia de ADN/métodos , Detección Precoz del Cáncer/métodos , Proteínas Oncogénicas Virales/genética , ADN Viral/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
9.
J Med Virol ; 96(6): e29753, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38895800

RESUMEN

Human papillomavirus (HPV) type 81 has recently become one of the most common low-risk HPV types; however, literature focusing on it is limited. This study aimed to analyze the reasons for the increased detection rate of HPV81 and investigate its evolving pathogenicity. We analyzed the detection rates and trends of HPV81 in 229 061 exfoliated cervical cell samples collected from 2014 to 2023; collected samples of HPV81 single infections from two different time periods; and analyzed the allele frequencies, positive selection, viral load, persistent infection capacity, and pathogenicity of E6 and E7 genotypes. We found that the detection rate of HPV81 ranked first among the low-risk types in exfoliated cervical cells and exhibited a significantly increasing trend (p < 0.001). The frequency of the E6 prototype allele of HPV81 (n = 317) was significantly increased (p = 0.018) and demonstrated the strongest adaptive capacity. The viral load and persistent infection capacity of the E6 prototype were significantly higher than those of the mutants, thus serving as key drivers for increasing the detection rate of HPV81 and enhancing its pathogenicity. The viral load was positively correlated with persistent infection capacity and pathogenicity. Persistent infection was a crucial factor in the pathogenicity of HPV81. Successful adaptive evolution of HPV81 is accompanied by enhanced pathogenicity.


Asunto(s)
Genotipo , Infecciones por Papillomavirus , Infección Persistente , Polimorfismo Genético , Carga Viral , Humanos , Infecciones por Papillomavirus/virología , Femenino , Infección Persistente/virología , Cuello del Útero/virología , Cuello del Útero/patología , Adulto , Papillomaviridae/genética , Papillomaviridae/patogenicidad , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Frecuencia de los Genes , Proteínas Oncogénicas Virales/genética , Virulencia/genética , Alphapapillomavirus/genética , Alphapapillomavirus/patogenicidad , Alphapapillomavirus/clasificación , Alphapapillomavirus/aislamiento & purificación , Virus del Papiloma Humano
10.
J Med Virol ; 96(6): e29746, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38884391

RESUMEN

Head and neck cancers (HNCs), primarily head and neck squamous cell carcinoma (HNSCC), are associated with high-risk human papillomavirus (HR HPV), notably HPV16 and HPV18. HPV status guides treatment and predicts outcomes, with distinct molecular pathways in HPV-driven HNSCC influencing survival rates. HNC incidence is rising globally, with regional variations reflecting diverse risk factors, including tobacco, alcohol, and HPV infection. Oropharyngeal cancers attributed to HPV have significantly increased, particularly in regions like the United States. The HPV16 genome, characterized by oncoproteins E6 and E7, disrupts crucial cell cycle regulators, including tumor protein p53 (TP53) and retinoblastoma (Rb), contributing to HNSCC pathogenesis. P16 immunohistochemistry (IHC) is a reliable surrogate marker for HPV16 positivity, while in situ hybridization and polymerase chain reaction (PCR) techniques, notably reverse transcription-quantitative PCR (RT-qPCR), offer sensitive HPV detection. Liquid-based RT-qPCR, especially in saliva, shows promise for noninvasive HPV detection, offering simplicity, cost-effectiveness, and patient compliance. These molecular advancements enhance diagnostic accuracy, guide treatment decisions, and improve patient outcomes in HNC management. In conclusion, advances in HPV detection and molecular understanding have significant clinical management implications. Integrating these advancements into routine practice could ultimately improve patient outcomes.


Asunto(s)
Neoplasias de Cabeza y Cuello , Infecciones por Papillomavirus , Humanos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicaciones , Neoplasias de Cabeza y Cuello/virología , Neoplasias de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 16/patogenicidad , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/aislamiento & purificación , Virus del Papiloma Humano
11.
J Med Virol ; 96(6): e29688, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38847316

RESUMEN

To meet the screening goal of WHO's 90-70-90 strategy aimed at eliminating cervical cancer (CC) by 2030, clinical validation of human papillomavirus (HPV) assays is essential to provide accurate and valid results through fulfilling three criteria of the international validation guidelines (IVGs). Previously, the clinical accuracy of the AmpFire® HPV Screening 16/18/HR assay (AmpFire assay) was reported but reproducibility data are lacking. Here, we aim to evaluate the intra- and inter-laboratory reproducibility of the AmpFire assay. The reproducibility of the isothermal AmpFire assay was assessed using 556 cervical cell samples collected from women attending CC screening and biobanked in a Belgian HPV national reference center. This assay detects HPV16, HPV18, and 12 other high-risk HPV (hrHPV) types (31/33/35/39/45/51/52/56/58/59/66/68) in aggregate. Lower 95% confidence interval bound around the assay's reproducibility should exceed 87%, with κ ≥ 0.50. Additionally, a literature review of the assay's clinical performance was performed. The AmpFire assay showed an excellent intralaboratory (96.4%, 95% CI:94.5-97.8%, κ = 0.920) and interlaboratory (95.3%, 95% CI:93.2-96.9%, κ = 0.897) reproducibility. One study demonstrated noninferior sensitivity of a prototype AmpFire assay targeting 15 hrHPV types (including HPV53) to detect CIN2+. However, clinical specificity became similar to the comparator after removing HPV53 from analyses. The low-cost and easy-to-use AmpFire assay presents excellent reproducibility and-after removing HPV53 from the targeted types-fulfills also clinical accuracy requirements. Inclusion of HPV53, which is not recognized as carcinogenic, comprises clinical specificity of screening assays.


Asunto(s)
Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Reproducibilidad de los Resultados , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Papillomaviridae/aislamiento & purificación , Bélgica , Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/normas , Adulto , Sensibilidad y Especificidad , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular/normas , Técnicas de Diagnóstico Molecular/métodos , Cuello del Útero/virología
12.
J Med Virol ; 96(6): e29649, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38812416

RESUMEN

Persistent infection with high-risk human papillomavirus (HPV) is recognized as the main cause for the development of anogenital cancers. This study prospectively evaluated the diagnostic performance of the novel Allplex-HPV28 assay with the Anyplex-II-HPV28 to detect and genotype HPV in 234 consecutive swabs and 32 biopsies of the anogenital tract from 265 patients with atypical findings in cytomorphological screening. Agreement in HPV-DNA detection between the Anyplex-II and Allplex-HPV28 assays was 99%. There was a notable diversity in the HPV-virome, with the most prevalent high-risk HPV types being 16, 53, 66, and 68. The agreement rates for detecting these genotypes exceeded 93% between the Anyplex-II and Allplex-HPV28 assays. Discrepancies in test results were solely noted for Anyplex-II-HPV28 results with a low signal intensity of "+", and for Allplex-HPV28 results with cycle thresholds of ≥36. The semi-quantitative analysis of HPV-DNA loads showed significant agreement between the Anyplex-II-HPV28 and Allplex-HPV28 assays (p < 0.001). Furthermore, HPV-DNA detection rates and mean HPV-DNA loads significantly correlated with the grade of abnormal changes identified in cytopathological assessment, being highest in cases of HSIL, condyloma accuminatum, and squamous cell carcinoma. Overall agreement rates for detecting specific HPV-types among the Anyplex-II and Allplex-HPV28 assays exceeded 99.5% in cases of atypical squamous cells, condyloma accuminatum, and squamous cell carcinoma. The novel Allplex-HPV28 assay shows good diagnostic performance in detecting and genotyping HPV commonly associated with anogenital cancers. Consequently, this assay could offer substantial potential for incorporation into future molecular screening programs for anogenital cancers in clinical settings.


Asunto(s)
Detección Precoz del Cáncer , Genotipo , Papillomaviridae , Infecciones por Papillomavirus , Humanos , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/diagnóstico , Femenino , Masculino , Papillomaviridae/genética , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Persona de Mediana Edad , Detección Precoz del Cáncer/métodos , Adulto , Anciano , Estudios Prospectivos , Técnicas de Diagnóstico Molecular/métodos , ADN Viral/genética , Técnicas de Genotipaje/métodos , Adulto Joven , Sensibilidad y Especificidad , Neoplasias del Ano/virología , Neoplasias del Ano/diagnóstico , Virus del Papiloma Humano , Alphapapillomavirus
13.
J Med Virol ; 96(6): e29716, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38818787

RESUMEN

Accumulating evidence has demonstrated that high-risk human papillomaviruses (HR-HPVs) are involved in the etiology of a subset of oropharyngeal squamous cell carcinoma (OPSCC). In this regard, the International Agency for Research on Cancer (IARC) has recommended direct molecular HPV testing. So far, there is no agreement on the most appropriate method for HPV detection on OPSCC formalin-fixed paraffin-embedded (FFPE) materials. In this study, we aimed to evaluate the performance of the high-sensitive SureX HPV assay in OPSCC FFPE tissues compared with LiPA-25 and p16ink4a immunostaining. A retrospective series of FFPE primary OPSCC cases were diagnosed between 2008 and 2019 and provided by the Henan Cancer Hospital, China. The level of agreement of two assays was determined using Cohen's Kappa (κ) statistics. A total of 230 FFPE OPSCC samples from tumor resections (n = 160) and diagnostic biopsies (n = 70) were detected. Sixty-six (28.7%) and 70 (30.4%) samples were identified as HPV-DNA-positive by LiPA-25 and SureX, respectively, of which HPV16 was largely the most common type (95.5% vs 94.3%). We found a perfect concordance between LiPA-25 and SureX for HPV-DNA status (κ = 0.906, 95% CI: 0.875-0.937) and for HPV16 (κ = 0.925, 95% CI: 0.897-0.953). In addition, SureX and p16ink4a immunostaining had a perfect concordance (κ = 0.917, 95% CI: 0.888-0.946). Moreover, the HPV-driven fraction, based on double positivity for HPV-DNA and p16ink4a, was similar between SureX (63 of 230, 27.4%) and LiPA-25 (60 of 230, 26.1%). Similar results were found in samples from resections and biopsies. SureX and LiPA-25 are comparable. SureX could be used for routine HPV-DNA detection and genotyping on archival OPSCC FFPE tissues.


Asunto(s)
ADN Viral , Genotipo , Proteínas Oncogénicas Virales , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Adhesión en Parafina , Humanos , Neoplasias Orofaríngeas/virología , Estudios Retrospectivos , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/diagnóstico , Persona de Mediana Edad , Masculino , Femenino , Proteínas Oncogénicas Virales/genética , Anciano , ADN Viral/genética , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomaviridae/clasificación , Reacción en Cadena de la Polimerasa/métodos , Técnicas de Genotipaje/métodos , China , Adulto , Formaldehído , Virus del Papiloma Humano
14.
J Med Virol ; 96(6): e29764, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38923577

RESUMEN

The cervicovaginal microbiome may contribute to human papillomavirus (HPV)-associated cervical carcinogenesis, but studies have been limited by low-resolution analysis methods. Using a high-resolution bioinformatics pipeline, we evaluated the relationship of the cervicovaginal microbiome with HPV and cervical intraepithelial neoplasia (CIN). The cervicovaginal microbiome of 186 women was characterized by sequencing 16S rRNA regions (V3-V4 and V5-V6) and annotated with the high-resolution ANCHOR pipeline. Samples were genotyped for HPV using the Roche-Cobas 4800 assay. We fitted logistic regression models using stepwise forward selection to select species (presence/absence) as correlates of CIN1+ and constructed a linear microbiome-based score using the regression coefficients. An HPV-based score was calculated from a separate logistic regression model to detect CIN1+ . Receiver operating characteristic curve analyses were performed; the area under the curve (AUC) and 95% confidence intervals (CI) were compared between scores. Overall, 66.7% of participants were HPV-positive. 77 unique species were identified: 8 using V3-V4, 48 using V5-V6, and 21 shared. Twelve species were retained via stepwise selection. The AUCs for the microbiome-, and HPV-based scores were 0.7656 (95% CI 0.6885-0.8426), and 0.7529 (95% CI 0.6855-0.8204), respectively. Bacterial species may be involved in cervical carcinogenesis as the microbiome- and HPV-based scores performed similarly for CIN1+ detection.


Asunto(s)
Carcinogénesis , Cuello del Útero , Microbiota , Papillomaviridae , Infecciones por Papillomavirus , ARN Ribosómico 16S , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Vagina , Humanos , Femenino , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/microbiología , Infecciones por Papillomavirus/complicaciones , Adulto , Vagina/microbiología , Vagina/virología , Cuello del Útero/microbiología , Cuello del Útero/virología , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/microbiología , Displasia del Cuello del Útero/microbiología , Displasia del Cuello del Útero/virología , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomaviridae/clasificación , ARN Ribosómico 16S/genética , Persona de Mediana Edad , Genotipo , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Adulto Joven , Virus del Papiloma Humano
15.
Sex Transm Infect ; 100(4): 252-255, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38641362

RESUMEN

OBJECTIVES: In this study, we compared the performance of a self-administered point-of-care test (POCT) for anal human papillomavirus (HPV) screening with laboratory gold-standard test in pre-exposure prophylaxis (PrEP) users and evaluated its feasibility. METHODS: We enrolled PrEP users from a local community-based PrEP service. Each participant self-collected an anal swab to test anal HPV with a PCR POCT capable of detecting 14 high-risk HPV genotypes. Anonymous questionnaires on self-sampling feasibility were completed. Participants were then referred to local clinics to undergo standard viral genotyping. Concordance between POCT and gold-standard test was measured with absolute agreement and Cohen's kappa. Receiver operating characteristic (ROC) curves were used to calculate POCT sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: 179 subjects got a valid POCT result, most of them men (98.3%) and men who have sex with men (90.4%). 68.2% tested positive for at least one high-risk HPV genotype on POCT. 150 feasibility questionnaires were collected: 92.7% of compilers found the self-swab easy to perform. For 178 subjects, a gold-standard test valid result was also available: 77% tested positive for at least one high-risk HPV genotype. The median time elapsed between the two tests was 9.8 months, due to COVID-19-related service interruptions. Agreement between POCT and gold-standard test was 79.3% (Cohen's kappa=0.49). POCT showed a sensitivity of 81.0%, a specificity of 73.8%, a PPV of 91.0% and an NPV of 54.4%. CONCLUSIONS: POCT showed a moderate agreement with gold-standard test and a discrete sensitivity and specificity, suggesting that it could be a useful and feasible additional tool for HPV screening, especially in low-resource and community-based settings.


Asunto(s)
Infecciones por Papillomavirus , Pruebas en el Punto de Atención , Profilaxis Pre-Exposición , Sensibilidad y Especificidad , Humanos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/prevención & control , Masculino , Adulto , Femenino , Tamizaje Masivo/métodos , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Canal Anal/virología , Estudios de Factibilidad , Persona de Mediana Edad , Homosexualidad Masculina/estadística & datos numéricos , Infecciones por VIH/diagnóstico , Infecciones por VIH/prevención & control , Adulto Joven , Autoevaluación
16.
Virol J ; 21(1): 140, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890675

RESUMEN

BACKGROUND: The persistent infection of high-risk Human papillomavirus(HPV) is considered the main cause of cervical intraepithelial neoplasia and cervical cancer. But various cervical lesions caused by HPV infection can be properly prevented by timely vaccination. However, the distribution of HPV genotypes varies geographically. METHODS: Retrospective analysis of high-risk HPV prevalence of 16,150 women from 2020 to 2022 in xianning of China. HPV genotyping was performed using a PCR-RDB Kit that can detect 18 high-risk HPV genotypes recommended by China's National Medical Products Administration. The prevalence of 18 high-risk HPV genotypes and their relationship with cervical lesions as well as vaccine efficacy were analyzed. RESULTS: A total of 2431 women were confirmed to have different types of high-risk HPV infections. The overall positive rate reached 15.05%(2431/16,150). The most prevalent high-risk HPV genotypes were HPV52, 16, 58, 53, and 51. The prevalence of high-risk HPV reached peak at age ≤ 20(20.95%) and age ≥ 61(20.56%). The most prevalent high-risk HPV genotypes were HPV16, 58, 18, 33 and 52 in cervical cancer cases, HPV16, 52, 58, 33 and 18 in CIN2/3 cases, and HPV52, 58, 16, 53 and 18 in CIN1 cases, respectively. CONCLUSION: HPV16, 58 and 18 are the most dangerous and carcinogenic genotypes in xianning, China. Conducting epidemiological investigations on high-risk HPV has significant clinical value in guiding HPV vaccination work.


Asunto(s)
Genotipo , Papillomaviridae , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , China/epidemiología , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Prevalencia , Adulto , Persona de Mediana Edad , Adulto Joven , Estudios Retrospectivos , Papillomaviridae/genética , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/epidemiología , Adolescente , Anciano , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/epidemiología , Vacunas contra Papillomavirus/administración & dosificación , Virus del Papiloma Humano
17.
Virol J ; 21(1): 133, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844960

RESUMEN

BACKGROUND: Early diagnosis and treatment of HPV persistent infection and cervical intraepithelial neoplasia, which have yet to be thoroughly characterized in Guangxi, Southwestern China, are the key preventative measures for the development of cervical cancer in women, particularly in HIV-infected women. METHODS: A retrospective study of 181 patients with HPV infection or cervical intraepithelial neoplasia who received surgical excision of lesions and were prospectively enrolled at the Fourth People's Hospital of Nanning between January 2018 and February 2023 was performed. HPV-infected patients were divided into two subgroups: HIV-infected and HIV/HPV-coinfected patients and compare differences between these groups. RESULTS: HPV16, 18, 52, and 58 were the most prevalent HPV genotypes. High-risk HPV was significantly co-infected with multiple genotypes (P = 0.0332). HIV-infected women were predisposed to HPV infection (P < 0.0001), and the development of cervical cancer at a young age (P = 0.0336) compared to HIV-uninfected women and the loop electrosurgical excision procedure (P = 0.0480) is preferred for the treatment. CONCLUSIONS: HIV infection may increase HPV prevalence and lead to cervical cancer development at a young age. The loop electrosurgical excision procedure is an efficient evaluation and treatment strategy for HIV-infected women suffering from cervical intraepithelial neoplasia.


Asunto(s)
Coinfección , Infecciones por VIH , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Infecciones por VIH/complicaciones , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/cirugía , Displasia del Cuello del Útero/complicaciones , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/cirugía , Coinfección/virología , China/epidemiología , Genotipo , Prevalencia , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Infección Persistente/virología , Adulto Joven
18.
Virol J ; 21(1): 129, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38840267

RESUMEN

BACKGROUND: Global human activities were significantly impacted by the emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by the 2019 novel coronavirus. This study aimed to investigate the prevalence and genotype distribution of HPV infection in Central Fujian Province during the pandemic. METHODS: Cervical samples were collected from 21,612 outpatients and 12,664 females who underwent physical examinations and HPV screening at the People's Hospital of Fujian Province in Fuzhou from April 2020 to April 2023. HPV detection and genotyping were conducted using PCR hybridization. RESULTS: The overall HPV infection rate was 16.1% during the COVID-19 pandemic, with the outpatient group exhibiting a greater infection rate (19.0%) than did the healthy group (12.3%). The top five high-risk HPV (HR-HPV) genotypes in both groups were HPV52, HPV53, HPV58, HPV16, and HPV51. Additionally, HPV81 and HPV43 were the two most common low-risk HPV (LR-HPV) genotypes in the patient group, while HPV81 and HPV42 were the two most common LR-HPV genotypes in the healthy group. The highest prevalence of HPV infection was observed in individuals aged ≤ 24 years (28.4%, 95% CI 25.9-30.9), followed by those aged ≥ 55 years (23.6%, 95% CI 21.6-24.7) and other age groups. The prevalence decreased from 23.0% (95% CI 22.4-23.7) in 2018-2019 to 13.8% (95% CI 12.0-15.5) in 2023. CONCLUSION: This study provides valuable insights into the prevalence and genotypes of HPV infection in the female population of Central Fujian Province from 2020 to 2023. The findings indicate that the prevalence of HPV infection in Central Fujian Province remains relatively low compared to the national average. Furthermore, the prevalence of HPV decreased during the COVID-19 pandemic; however, as the pandemic waned, there was potential for an increase in HPV infection rates. Therefore, it is crucial to strengthen HPV screening and vaccination strategies to prevent the potential spread of HPV.


Asunto(s)
COVID-19 , Genotipo , Papillomaviridae , Infecciones por Papillomavirus , Humanos , Femenino , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , China/epidemiología , Adulto , Prevalencia , COVID-19/epidemiología , COVID-19/virología , Persona de Mediana Edad , Adulto Joven , Papillomaviridae/genética , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/clasificación , Adolescente , Anciano , Cuello del Útero/virología , Virus del Papiloma Humano
19.
Gynecol Oncol ; 184: 96-102, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38301312

RESUMEN

BACKGROUND: Little is known about cervical cancer screening strategy utilization (cytology alone, cytology plus high-risk human papillomavirus [HPV] testing [cotesting], primary HPV testing) and test results in the United States. METHODS: Data from the Centers for Disease Control and Prevention's National Breast and Cervical Cancer Early Detection Program were analyzed for 199,578 persons aged 21-65 years screened from 2019 to 2020. Screening test utilization and results were stratified by demographic characteristics and geographic region. Age-standardized pooled HPV test positivity and genotyping test positivity were estimated within cytology result categories. RESULTS: Primary HPV testing was performed in 592 persons (0.3%). Among the remaining 176,290 persons aged 30-65 years, cotesting was utilized in 72.1% (95% confidence interval [CI] 71.9-72.3%), and cytology alone was utilized in 27.9% (95% CI 27.7-28.1%). Utilization of cytology alone varied by geographic region, ranging from 18.3% (95% CI 17.4-19.1%) to 49.0% (95% CI 48.4-49.6%). HPV genotyping test utilization among those with positive pooled HPV test results was 33.9%. In persons aged ≥30 years, variations in age-adjusted test results by region were observed for pooled HPV-positive test results and for HPV genotyping-positive test results. CONCLUSIONS: Cervical cancer screening strategy utilization and test results vary substantially by geographic region within a national screening program. Variation in utilization may be due to regional differences in screening test availability or the preferences of healthcare systems, screened persons and/or clinicians. Test result variations may reflect differing risk factors for HPV infections by geographic region.


Asunto(s)
Detección Precoz del Cáncer , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/epidemiología , Persona de Mediana Edad , Adulto , Detección Precoz del Cáncer/estadística & datos numéricos , Detección Precoz del Cáncer/métodos , Estados Unidos/epidemiología , Anciano , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/epidemiología , Adulto Joven , Frotis Vaginal/estadística & datos numéricos , Papillomaviridae/aislamiento & purificación , Papillomaviridae/genética
20.
Am J Obstet Gynecol ; 230(6): 655.e1-655.e10, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38336125

RESUMEN

BACKGROUND: In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression. OBJECTIVE: This study aimed to describe human papillomavirus HPV type-specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. STUDY DESIGN: We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF10-DEIA-LiPA25 system (DNA ELISA [enzyme-linked immunosorbent assay] HPV SPF10 kit and RHA HPV SPF10-LiPA25 kit). Persistence/progression was defined as having a record of cervical intraepithelial neoplasia grade ≥2 in the DPDB determined on the last and worst diagnosis on a biopsy or loop electrosurgical excision procedure specimen during follow-up. We estimated the relative risk (95% confidence interval) of persistence/progression using a modified Poisson model. RESULTS: A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37-1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03-1.61), whereas no differences were observed across age groups. CONCLUSION: The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women.


Asunto(s)
Progresión de la Enfermedad , Genotipo , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/cirugía , Adulto , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/patología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Adulto Joven , Estudios de Cohortes , Clasificación del Tumor , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Espera Vigilante , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Dinamarca/epidemiología , Virus del Papiloma Humano
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