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Although most cervical human papillomavirus type 16 (HPV16) infections become undetectable within 1-2 years, persistent HPV16 causes half of all cervical cancers. We used a novel HPV whole-genome sequencing technique to evaluate an exceptionally large collection of 5,570 HPV16-infected case-control samples to determine whether viral genetic variation influences risk of cervical precancer and cancer. We observed thousands of unique HPV16 genomes; very few women shared the identical HPV16 sequence, which should stimulate a careful re-evaluation of the clinical implications of HPV mutation rates, transmission, clearance, and persistence. In case-control analyses, HPV16 in the controls had significantly more amino acid changing variants throughout the genome. Strikingly, E7 was devoid of variants in precancers/cancers compared to higher levels in the controls; we confirmed this in cancers from around the world. Strict conservation of the 98 amino acids of E7, which disrupts Rb function, is critical for HPV16 carcinogenesis, presenting a highly specific target for etiologic and therapeutic research.
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Alphapapillomavirus/genética , Alphapapillomavirus/aislamiento & purificación , Carcinoma/virología , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/virología , Adulto , Alphapapillomavirus/clasificación , Estudios de Casos y Controles , Femenino , Genoma Viral , Humanos , Persona de Mediana Edad , Proteínas E7 de Papillomavirus/genética , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
Multicancer detection (MCD) tests use a single, easily obtainable biospecimen, such as blood, to screen for more than one cancer concurrently. MCD tests can potentially be used to improve early cancer detection, including cancers that currently lack effective screening methods. However, these tests have unknown and unquantified benefits and harms. MCD tests differ from conventional cancer screening tests in that the organ responsible for a positive test is unknown, and a broad diagnostic workup may be necessary to confirm the location and type of underlying cancer. Among two prospective studies involving greater than 16,000 individuals, MCD tests identified those who had some cancers without currently recommended screening tests, including pancreas, ovary, liver, uterus, small intestine, oropharyngeal, bone, thyroid, and hematologic malignancies, at early stages. Reported MCD test sensitivities range from 27% to 95% but differ by organ and are lower for early stage cancers, for which treatment toxicity would be lowest and the potential for cure might be highest. False reassurance from a negative MCD result may reduce screening adherence, risking a loss in proven public health benefits from standard-of-care screening. Prospective clinical trials are needed to address uncertainties about MCD accuracy to detect different cancers in asymptomatic individuals, whether these tests can detect cancer sufficiently early for effective treatment and mortality reduction, the degree to which these tests may contribute to cancer overdiagnosis and overtreatment, whether MCD tests work equally well across all populations, and the appropriate diagnostic evaluation and follow-up for patients with a positive test.
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Detección Precoz del Cáncer , Neoplasias , Humanos , Neoplasias/diagnóstico , Detección Precoz del Cáncer/métodos , Investigación Biomédica Traslacional , Sensibilidad y Especificidad , Tamizaje Masivo/métodosRESUMEN
Despite being highly preventable, cervical cancer is the fourth most common cancer and cause of cancer death in women globally. In low-income countries, cervical cancer is often the leading cause of cancer-related morbidity and mortality. Women living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome are at a particularly high risk of cervical cancer because of an impaired immune response to human papillomavirus, the obligate cause of virtually all cervical cancers. Globally, approximately 1 in 20 cervical cancers is attributable to HIV; in sub-Saharan Africa, approximately 1 in 5 cervical cancers is due to HIV. Here, the authors provide a critical appraisal of the evidence to date on the impact of HIV disease on cervical cancer risk, describe key methodologic issues, and frame the key outstanding research questions, especially as they apply to ongoing global efforts for prevention and control of cervical cancer. Expanded efforts to integrate HIV care with cervical cancer prevention and control, and vice versa, could assist the global effort to eliminate cervical cancer as a public health problem.
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Infecciones por VIH/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Detección Precoz del Cáncer , Femenino , Humanos , Huésped Inmunocomprometido , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Lesiones Precancerosas/terapia , Prevención Primaria , Prevención SecundariaRESUMEN
Timely follow-up for positive cancer screening results remains suboptimal, and the evidence base to inform decisions on optimizing the timeliness of diagnostic testing is unclear. This systematic review evaluated published studies regarding time to follow-up after a positive screening for breast, cervical, colorectal, and lung cancers. The quality of available evidence was very low or low across cancers, with potential attenuated or reversed associations from confounding by indication in most studies. Overall, evidence suggested that the risk for poorer cancer outcomes rises with longer wait times that vary within and across cancer types, which supports performing diagnostic testing as soon as feasible after the positive result, but evidence for specific time targets is limited. Within these limitations, we provide our opinion on cancer-specific recommendations for times to follow-up and how existing guidelines relate to the current evidence. Thresholds set should consider patient worry, potential for loss to follow-up with prolonged wait times, and available resources. Research is needed to better guide the timeliness of diagnostic follow-up, including considerations for patient preferences and existing barriers, while addressing methodological weaknesses. Research is also needed to identify effective interventions for reducing wait times for diagnostic testing, particularly in underserved or low-resource settings. CA Cancer J Clin 2018;68:199-216. © 2018 American Cancer Society.
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Continuidad de la Atención al Paciente , Detección Precoz del Cáncer , Neoplasias/diagnóstico , Biopsia , Diagnóstico Tardío , Diagnóstico por Imagen , Humanos , Tiempo de TratamientoRESUMEN
BACKGROUND: Systematic evaluations of cancer risk in people living with HIV or AIDS (PLHIV) and solid organ transplant recipients provide unique insights into the role of the immune system in cancer development. In this systematic review and meta-analysis, we expand previous analyses of cancer risk for these two immunocompromised populations. METHODS: We considered studies published in English and listed on PubMed or Embase up to July 1, 2022. Studies were eligible for inclusion if they used population-based registries and compared cancer incidence in PLHIV or solid organ transplant recipients with the general population in the same geographical area. We extracted the number of observed site-specific cancers and expected cases and calculated meta-standardised incidence ratios for cancer within PLHIV and solid organ transplant recipients. In solid organ transplant recipients meta-standardised incidence ratios were compared by organ type. This project is registered on PROSPERO, CRD42022366679. FINDINGS: 46 studies in PLHIV and 67 in solid organ transplant recipients were included in the analysis. Meta-standardised incidence ratios for cancers associated with human papillomavirus were increased in both populations; the highest meta-standardised incidence ratio in PLHIV was anal cancer (37·28 [95% CI 23·65-58·75], I2=97·4%), and in solid organ transplant recipients was cutaneous squamous cell carcinoma (45·87 [31·70-66·38], I2=99·0%). Meta-standardised incidence ratios were significantly increased for most non-HPV viral-infection-related cancers in both populations; the highest standard incidence ratios were for Kaposi sarcoma (PLHIV: 801·52 [95% CI 200·25-3208·13], I2=100·0%; solid organ transplant recipients: 47·31 [23·09-96·95], I2=87·7%) and non-Hodgkin lymphoma (32·53 [19·64-53·87], I2=99·8%; 10·24 [8·48-12·35], I2=94·9%). Eight types of cancer with no known viral cause showed an increased risk in solid organ transplant recipients only; no cancer type showed increased risk in PLHIV only. INTERPRETATION: Cancer risk was increased for a range of infection-related cancers in both PLHIV and solid organ transplant recipients, but divergent results in these and other cancers have emerged. The cancer risk patterns probably reflect variances in the degree of impaired immunity, exposure to carcinogenic viruses, and perhaps exposure to carcinogenic immunosuppressive agents. FUNDING: US National Cancer Institute, National Institutes of Health.
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Infecciones por VIH , Neoplasias , Trasplante de Órganos , Receptores de Trasplantes , Humanos , Trasplante de Órganos/efectos adversos , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Neoplasias/epidemiología , Incidencia , Receptores de Trasplantes/estadística & datos numéricos , Huésped Inmunocomprometido , Factores de Riesgo , Medición de Riesgo , Femenino , MasculinoRESUMEN
The requirement of large-scale expensive cancer screening trials spanning decades creates considerable barriers to the development, commercialisation, and implementation of novel screening tests. One way to address these problems is to use surrogate endpoints for the ultimate endpoint of interest, cancer mortality, at an earlier timepoint. This Review aims to highlight the issues underlying the choice and use of surrogate endpoints for cancer screening trials, to propose criteria for when and how we might use such endpoints, and to suggest possible candidates. We present the current landscape and challenges, and discuss lessons and shortcomings from the therapeutic trial setting. It is hugely challenging to validate a surrogate endpoint, even with carefully designed clinical studies. Nevertheless, we consider whether there are candidates that might satisfy the requirements defined by research and regulatory bodies.
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Detección Precoz del Cáncer , Neoplasias , Humanos , Detección Precoz del Cáncer/métodos , Neoplasias/diagnóstico , Biomarcadores de Tumor/análisis , Ensayos Clínicos como Asunto , Proyectos de Investigación/normas , Biomarcadores/análisis , Determinación de Punto FinalRESUMEN
There are marked disparities in cancer survival in low-income countries compared to high-income countries, yet population-based data in the first is largely lacking. In this study, data from the national cancer registry of Rwanda were examined for 542 patients diagnosed with eight of the most common cancers of adults stomach (C16), colorectum (C18-20), liver (C22), breast (female) (C50), cervix (C53), ovary (C56), prostate (C61), and non-Hodgkin lymphomas (C82-85) between 2014 and 2017. Subjects were randomly selected for active followed-up to calculate 1-, 3-, and 5-year observed and relative survival (RS) by cancer type and stage. Overall, 53.7% of cases had died within 5 years of diagnosis. Five-year RS varied by malignancy and ranged from 17.6% (95% confidence interval [CI]: 6.7%-32.6%) for liver cancer to 68% (CI: 51.6%-79.8%) for cancers of the prostate. Stage was assigned for 71.6% of patients (n = 388 of 542), with over half (58%) having advanced stage (III/IV) at diagnosis. For all except liver and ovary, stage was a strong predictor of survival; for example, three-year observed survival was 90.9% and 44.8% (p-value: .002) for early and advanced breast cancer, respectively. This study demonstrates that stage specific survival can be obtained from population based cancer registries in sub Saharan Africa, data that are invaluable for international benchmarking, and for local planning and evaluation of cancer control programs.
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Estadificación de Neoplasias , Neoplasias , Sistema de Registros , Humanos , Rwanda/epidemiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Neoplasias/mortalidad , Neoplasias/diagnóstico , Neoplasias/epidemiología , Anciano , Adulto Joven , Tasa de Supervivencia , Anciano de 80 o más Años , AdolescenteRESUMEN
Assessing the risk of cancer among people living with HIV (PLHIV) in the current era of antiretroviral therapy (ART) is crucial, given their increased susceptibility to many types of cancer and prolonged survival due to ART exposure. Our study aims to compare the association between HIV infection and specific cancer sites in Rwanda. Population-based cancer registry data were used to identify cancer cases in both PLHIV and HIV-negative persons. A probabilistic record linkage approach between the HIV and cancer registries was used to supplement HIV status ascertainment in the cancer registry. Associations between HIV infection and different cancer types were evaluated using unconditional logistic regression models. We performed several sensitivity analyses to assess the robustness of our findings and to evaluate the potential impact of different assumptions on our results. From 2007 to 2018, the cancer registry recorded 17,679 cases, of which 7% were diagnosed among PLHIV. We found significant associations between HIV infection and Kaposi's Sarcoma (KS) (adjusted odds ratio [OR]: 29.1, 95% CI: 23.2-36.6), non-Hodgkin lymphoma (NHL) (1.6, 1.3-2.0), Hodgkin lymphoma (HL) (1.6, 1.1-2.4), cervical (2.3, 2.0-2.7), vulvar (4.0, 2.5-6.5), penile (3.0, 2.0-4.5), and eye cancers (2.2, 1.6-3.0). Men living with HIV had a higher risk of anal cancer (3.1, 1.0-9.5) than men without HIV, but women living with HIV did not have higher risk than women without HIV (1.0, 0.2-4.3). Our study found that in an era of expanded ART coverage in Rwanda, HIV is associated with a broad range of cancers, particularly those linked to viral infections.
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OBJECTIVES: The longer-term impact of introducing human papillomavirus (HPV) testing into routine cervical cancer screening on precancer and cancer rates by histologic type has not been well described. Calendar trends in diagnoses were examined using data from Kaiser Permanente Northern California, which introduced triennial HPV and cytology co-testing in 2003 for women aged ≥30 years. METHODS: We examined trends in cervical precancer (cervical intraepithelial neoplasia grade 3 [CIN3] and adenocarcinoma in situ [AIS]) and cancer (squamous cell carcinoma [SCC] and adenocarcinoma [ADC]) diagnoses per 1000 screened during 2003-2018. We examined ratios of squamous vs. glandular diagnoses (SCC:ADC and CIN3:AIS). RESULTS: CIN3 and AIS diagnoses increased approximately 2% and 3% annually, respectively (ptrend < 0.001 for both). While SCC diagnoses decreased by 5% per annually (ptrend < 0.001), ADC diagnoses did not change. These patterns were generally observed within each age group (30-39, 40-49, and 50-64 years). ADC diagnoses per 1000 screened did not change even among those who underwent co-testing starting in 2003-2006. SCC:ADC decreased from approximately 2.5:1 in 2003-2006 to 1.3:1 in 2015-2018 while the CIN3:AIS remained relatively constant, â¼10:1. CONCLUSIONS: Since its introduction at KPNC, co-testing increased the detection of CIN3 over time, which likely caused a subsequent reduction of SCC. However, there has been no observed decrease in ADC. One possible explanation for lack of effectiveness against ADC is the underdiagnosis of AIS. Novel strategies to identify and treat women at high risk of ADC need to be developed and clinically validated.
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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/epidemiología , Neoplasias del Cuello Uterino/patología , California/epidemiología , Adulto , Persona de Mediana Edad , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/patología , Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/estadística & datos numéricos , Detección Precoz del Cáncer/tendencias , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Adenocarcinoma in Situ/patología , Adenocarcinoma in Situ/diagnóstico , Adenocarcinoma in Situ/epidemiología , Adenocarcinoma in Situ/virología , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/virología , Lesiones Precancerosas/patología , Anciano , Frotis Vaginal/tendencias , Frotis Vaginal/métodos , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Adenocarcinoma/virología , Virus del Papiloma Humano , CitologíaRESUMEN
BACKGROUND: The lack of accurate population-based information on childhood cancer stage and survival in low-income countries is a barrier to improving childhood cancer outcomes. METHODS: In this study, data from the Rwanda National Cancer Registry (RNCR) were examined for children aged 0-14 diagnosed in 2013-2017 for the eight most commonly occurring childhood cancers: acute lymphoblastic leukaemia, Hodgkin lymphoma (HL), Burkitt lymphoma (BL), non-Hodgkin lymphoma excluding BL, retinoblastoma, Wilms tumour, osteosarcoma and rhabdomyosarcoma. Utilising the Toronto Childhood Cancer Stage Guidelines Tier 1, the study assigned stage at diagnosis to all, except HL, and conducted active follow-ups to calculate 1-, 3- and 5-year observed and relative survival by cancer type and stage at diagnosis. RESULTS: The cohort comprised 412 children, of whom 49% (n = 202) died within 5 years of diagnosis. Five-year survival ranged from 28% (95% confidence interval [CI]: 12.5%-45.6%) for BL to 68% (CI: 55%-78%) for retinoblastoma. For the cancers for which staging was carried out, it was assigned for 83% patients (n = 301 of 362), with over half (58%) having limited or localised stage at diagnosis. Stage was a strong predictor of survival; for example, 3-year survival was 70% (95% CI: 45.1%-85.3%) and 11.8% (2.0%-31.2%) for limited and advanced non-HL, respectively (p < .001). CONCLUSION: This study is only the second to report on stage distribution and stage-specific survival for childhood cancers in sub-Saharan Africa. It demonstrates the feasibility of the Toronto Stage Guidelines in a low-resource setting, and highlights the value of population-based cancer registries in aiding our understanding of the poor outcomes experienced by this population.
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Estadificación de Neoplasias , Neoplasias , Sistema de Registros , Humanos , Rwanda/epidemiología , Masculino , Preescolar , Niño , Femenino , Lactante , Adolescente , Tasa de Supervivencia , Recién Nacido , Neoplasias/mortalidad , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias/patología , Estudios de Seguimiento , PronósticoRESUMEN
ABSTRACT: This Research Letter summarizes all updates to the 2019 Guidelines through September 2023, including: endorsement of the 2021 Opportunistic Infections guidelines for HIV+ or immunosuppressed patients; clarification of use of human papillomavirus testing alone for patients undergoing observation for cervical intraepithelial neoplasia 2; revision of unsatisfactory cytology management; clarification that 2012 guidelines should be followed for patients aged 25 years and older screened with cytology only; management of patients for whom colposcopy was recommended but not completed; clarification that after treatment for cervical intraepithelial neoplasia 2+, 3 negative human papillomavirus tests or cotests at 6, 18, and 30 months are recommended before the patient can return to a 3-year testing interval; and clarification of postcolposcopy management of minimally abnormal results.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Embarazo , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/terapia , Consenso , Gestión de Riesgos , Colposcopía , Frotis Vaginal , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , PapillomaviridaeRESUMEN
Human papillomavirus (HPV) testing for cervical screening increases diagnosis of precancer and reduces the incidence of cervical cancer more than cytology alone. However, real-world evidence from diverse practice settings is lacking for the United States (U.S.) to support clinician adoption of primary HPV screening. Using a population-based registry, which captures all cervical cytology (with or without HPV testing) and all cervical biopsies, we conducted a real-world evidence study of screening in women aged 30 to 64 years across the entire state of New Mexico. Negative cytology was used to distinguish cotests from reflex HPV tests. A total of 264 198 cervical screening tests (with exclusions based on clinical history) were recorded as the first screening test between 2014 and 2017. Diagnoses of cervical intraepithelial neoplasia grades 2 or 3 or greater (CIN2+, CIN3+) from 2014 to 2019 were the main outcomes. Of cytology-negative screens, 165 595 (67.1%) were cotests and 4.8% of these led to biopsy within 2 years vs 3.2% in the cytology-only group. Among cytology-negative, HPV tested women, 347 of 398 (87.2%) CIN2+ cases were diagnosed in HPV-positive women, as were 147 of 164 (89.6%) CIN3+ cases. Only 29/921 (3.2%) CIN3+ and 67/1964 (3.4%) CIN2+ cases were diagnosed in HPV-negative, cytology-positive women with biopsies. Under U.S. opportunistic screening, across a diversity of health care delivery practices, and in a population suffering multiple disparities, we show adding HPV testing to cytology substantially increased the yield of CIN2+ and CIN3+. CIN3+ was rarely diagnosed in HPV-negative women with abnormal cytology, supporting U.S. primary HPV-only screening.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Estados Unidos/epidemiología , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Detección Precoz del Cáncer , Cuello del Útero/patología , Displasia del Cuello del Útero/diagnóstico , Tamizaje Masivo , Frotis Vaginal , New Mexico , PapillomaviridaeRESUMEN
BACKGROUND: Human papillomavirus (HPV) testing on self-samples represents a great opportunity to increase cervical cancer screening uptake among under-screened women. METHODS: A systematic review and meta-analysis on randomised controlled trials (RCTs) were performed to update the evidence on the efficacy of strategies for offering self-sampling kits for HPV testing compared to conventional invitations and to compare different self-sampling invitation scenarios. Four experimental invitational scenarios were considered. Women in the control group were invited for screening according to existing practice: collection of a cervical specimen by a healthcare professional. Random-effects models were used to pool proportions, relative participation rates and absolute participation differences. RESULTS: Thirty-three trials were included. In the intention-to-treat analysis, all self-sampling invitation scenarios were more effective in reaching under-screened women compared to controls. Pooled participation difference (PD) and 95% confidence interval (CI) for experimental vs. control was 13.2% (95% CI = 11.0-15.3%) for mail-to-all, 4.4% (95% CI = 1.2-7.6%) for opt-in, 39.1% (95% CI = 8.4-69.9%) for community mobilisation & outreach and 28.1% (23.5-32.7%) for offer at healthcare service. PD for the comparison opt-in vs. mail-to-all, assessed in nine trials, was -8.2% (95% CI = -10.8 to -5.7%). DISCUSSION: Overall, screening participation was higher among women invited for self-sampling compared to control, regardless of the invitation strategy used. Opt-in strategies were less effective than send-to-all strategies.
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Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Humanos , Detección Precoz del Cáncer , Tamizaje Masivo , Manejo de Especímenes , Papillomaviridae , Frotis Vaginal , AutocuidadoRESUMEN
BACKGROUND: Cervical screening has not effectively controlled cervical adenocarcinoma (AC). Human papillomavirus (HPV) testing is recommended for cervical screening but the optimal management of HPV-positive individuals to prevent AC remains a question. Cytology and HPV typing are two triage options to predict the risk of AC. We combined two potential biomarkers (atypical glandular cell, AGC, cytology and HPV-types 16, 18, or 45) to assess their joint effect on detecting AC. METHODS: Kaiser Permanente Northern California (KPNC) used triennial co-testing with cytology and HPV testing (positive/negative) for routine cervical screening between 2003 and 2020. HPV typing of a sample of residual HPV test specimens was performed on a separate cohort selected from KPNC (Persistence and Progression, PaP, cohort). We compared risk of prevalent and incident histologic AC/AIS (adenocarcinoma in situ) associated with preceding combinations of cytologic results and HPV typing. Risk of squamous cell cancer (SCC)/cervical intraepithelial neoplasia grade 3 (CIN3) (SCC/CIN3) was also included for comparison. RESULTS: Among HPV-positive individuals in PaP cohort, 99% of prevalent AC and 96% of AIS were linked to HPV-types 16, 18, or 45 (denoted HPV 16/18/45). Although rare (0.09% of screening population), the concurrent detection of HPV 16/18/45 with AGC cytology predicted a highly elevated relative risk of underlying histologic AC/AIS; the absolute risk of diagnosing AC/AIS was 12% and odds ratio (OR) was 1341 (95%CI:495-3630) compared to patients with other high-risk HPV types and normal cytology. Cumulatively (allowing non-concurrent results), approximately one-third of the AC/AIS cases ever had HPV 16/18/45 and AGC cytology (OR = 1785; 95%CI:872-3656). AGC was not as strongly associated with SCC/CIN3. CONCLUSION: Detection of HPV 16/18/45 positivity elevates risk of adenocarcinoma, particularly if AGC cytology is also found.
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Adenocarcinoma , Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/patología , Papillomavirus Humano 16 , Detección Precoz del Cáncer , Papillomavirus Humano 18 , Displasia del Cuello del Útero/patología , Frotis Vaginal , PapillomaviridaeRESUMEN
OBJECTIVE: To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally. METHODS: Women aged 30-49 years were prospectively enrolled and offered primary HPV testing using either self-collected or provider-collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation. If ineligible, they were referred for excision with a loop electrosurgical excision procedure, for cold knife conization, or for cervical biopsy if malignancy was suspected. RESULTS: Between January 2020 and January 2023, 9014 patients underwent cervical cancer screening. Median age was 37 years (range 30-49) and 4122 women (45.7%) were patients living with HIV. Most (n=8792, 97.5%) chose self-collection. The HPV positivity rate was 31.1% overall and 39.5% among patients living with HIV. Of the 2805 HPV-positive patients, 2588 (92.3%) returned for all steps of their diagnostic work-up and treatment, including ablation (n=2383, 92.1%), loop electrosurgical excision procedure (n=169, 6.5%), and cold knife conization (n=5, 0.2%). Thirty-one patients (1.2%) were diagnosed with cancer and referred to gynecologic oncology. CONCLUSION: It is feasible to perform cervical cancer screening with primary HPV testing and follow-up in low-resource settings. Participants preferred self-collection, and the majority of screen-positive patients completed all steps of their diagnostic work-up and treatment. Our findings provide important information for further implementation and scale-up of cervical cancer screening and treatment services as part of the WHO global strategy for the elimination of cervical cancer.
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Infecciones por VIH , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/prevención & control , Infecciones por Papillomavirus/diagnóstico , Detección Precoz del Cáncer/métodos , Mozambique/epidemiología , Papillomaviridae , Tamizaje Masivo/métodos , Infecciones por VIH/diagnósticoRESUMEN
BACKGROUND: Human papillomavirus-related biomarkers such as p16/Ki-67 "dual-stain" (DS) cytology have shown promising clinical performance for anal cancer screening. Here, we assessed the performance of automated evaluation of DS cytology (automated DS) to detect anal precancer in men who have sex with men (MSM) and are living with human immunodeficiency virus (HIV). METHODS: We conducted a cross-sectional analysis of 320 MSM with HIV undergoing anal cancer screening and high-resolution anoscopy (HRA) in 2009-2010. We evaluated the performance of automated DS based on a deep-learning classifier compared to manual evaluation of DS cytology (manual DS) to detect anal intraepithelial neoplasia grade 2 or 3 (AIN2+) and grade 3 (AIN3). We evaluated different DS-positive cell thresholds quantified by the automated approach and modeled performance compared with other screening strategies in a hypothetical population of MSM with HIV. RESULTS: Compared with manual DS, automated DS had significantly higher specificity (50.9% vs 42.2%; Pâ <â .001) and similar sensitivity (93.2% vs 92.1%) for detection of AIN2+. Human papillomavirus testing with automated DS triage was significantly more specific than automated DS alone (56.5% vs 50.9%; Pâ <â .001), with the same sensitivity (93.2%). In a modeled analysis assuming a 20% AIN2+ prevalence, automated DS detected more precancers than manual DS and anal cytology (186, 184, and 162, respectively) and had the lowest HRA referral rate per AIN2+ case detected (3.1, 3.5, and 3.3, respectively). CONCLUSIONS: Compared with manual DS, automated DS detects the same number of precancers, with a lower HRA referral rate.
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Alphapapillomavirus , Neoplasias del Ano , Infecciones por VIH , Infecciones por Papillomavirus , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Antígeno Ki-67/análisis , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Estudios Transversales , Colorantes , Papillomaviridae , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , VIHRESUMEN
We conducted a meta-analysis of test agreement/concordance between human papillomavirus (HPV) testing in self-collected vs clinician-collected samples in 26 studies (10 071 participants) updating a previous meta-analysis on accuracy for cervical precancer. Pooled overall agreement was 88.7% (95% CI: 86.3%-90.9%), positive agreement was 84.6% (95% CI: 79.9%-88.7%), negative agreement was 91.7% (95% CI: 89.1%-94.0%) and kappa was 0.72 (95% CI: 0.66-0.78). Subgroup meta-analyses suggested higher overall agreement for target amplification-based DNA assays (90.4%) compared to signal amplification-based DNA assays (86.7%; P = .175) or RNA assays (82.3%; P < .001). HPV test agreement/concordance targets may provide criteria to extend existing validations toward alternative sampling approaches and devices/storage media.
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Alphapapillomavirus , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Alphapapillomavirus/genética , ADN , ADN Viral/análisis , ADN Viral/genética , Detección Precoz del Cáncer , Femenino , Humanos , Papillomaviridae/genética , Infecciones por Papillomavirus/diagnóstico , Sensibilidad y Especificidad , Manejo de Especímenes , Neoplasias del Cuello Uterino/diagnóstico , Frotis VaginalRESUMEN
Necessary stages of cervical carcinogenesis include acquisition of a carcinogenic human papillomavirus (HPV) type, persistence associated with the development of precancerous lesions, and invasion. Using prospective data from immunocompetent women in the Guanacaste HPV Natural History Study (NHS), the ASCUS-LSIL Triage Study (ALTS) and the Costa Rica HPV Vaccine Trial (CVT), we compared the early natural history of HPV types to inform transition probabilities for health decision models. We excluded women with evidence of high-grade cervical abnormalities at any point during follow-up and restricted the analysis to incident infections in all women and prevalent infections in young women (aged <30 years). We used survival approaches accounting for interval-censoring to estimate the time to clearance distribution for 20 529 HPV infections (64% were incident and 51% were carcinogenic). Time to clearance was similar across HPV types and risk classes (HPV16, HPV18/45, HPV31/33/35/52/58, HPV 39/51/56/59 and noncarcinogenic HPV types); and by age group (18-29, 30-44 and 45-54 years), among carcinogenic and noncarcinogenic infections. Similar time to clearance across HPV types suggests that relative prevalence can predict relative incidence. We confirmed that there was a uniform linear association between incident and prevalent infections for all HPV types within each study cohort. In the absence of progression to precancer, we observed similar time to clearance for incident infections across HPV types and risk classes. A singular clearance function for incident HPV infections has important implications for the refinement of microsimulation models used to evaluate the cost-effectiveness of novel prevention technologies.
Asunto(s)
Alphapapillomavirus , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Papillomaviridae , Estudios Prospectivos , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/prevención & controlRESUMEN
BACKGROUND: Cancer incidence is higher in men than in women at most shared anatomic sites for currently unknown reasons. The authors quantified the extent to which behaviors (smoking and alcohol use), anthropometrics (body mass index and height), lifestyles (physical activity, diet, medications), and medical history collectively explain the male predominance of risk at 21 shared cancer sites. METHODS: Prospective cohort analyses (n = 171,274 male and n = 122,826 female participants; age range, 50-71 years) in the National Institutes of Health-AARP Diet and Health Study (1995-2011). Cancer-specific Cox regression models were used to estimate male-to-female hazard ratios (HRs). The degree to which risk factors explained the observed male-female risk disparity was quantified using the Peters-Belson method. RESULTS: There were 26,693 incident cancers (17,951 in men and 8742 in women). Incidence was significantly lower in men than in women only for thyroid and gallbladder cancers. At most other anatomic sites, the risks were higher in men than in women (adjusted HR range, 1.3-10.8), with the strongest increases for bladder cancer (HR, 3.33; 95% confidence interval [CI], 2.93-3.79), gastric cardia cancer (HR, 3.49; 95% CI, 2.26-5.37), larynx cancer (HR, 3.53; 95% CI, 2.46-5.06), and esophageal adenocarcinoma (HR, 10.80; 95% CI, 7.33-15.90). Risk factors explained a statistically significant (nonzero) proportion of the observed male excess for esophageal adenocarcinoma and cancers of liver, other biliary tract, bladder, skin, colon, rectum, and lung. However, only a modest proportion of the male excess was explained by risk factors (ranging from 50% for lung cancer to 11% for esophageal adenocarcinoma). CONCLUSIONS: Men have a higher risk of cancer than women at most shared anatomic sites. Such male predominance is largely unexplained by risk factors, underscoring a role for sex-related biologic factors.
Asunto(s)
Adenocarcinoma , Adenocarcinoma/epidemiología , Anciano , Neoplasias Esofágicas , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Factores SexualesRESUMEN
BACKGROUND: Cervical cancer screening participation is suboptimal in most settings. We assessed whether human papillomavirus (HPV) self-sampling may increase screening participation among long-term non-attenders in Norway. METHODS: A pragmatic randomised controlled trial with participation as the primary outcome was initiated in the national cervical screening programme in March 2019. A random sample of 6000 women aged 35-69 years who had not attended screening for at least 10 years were randomised 1:1:1 to receive either (i) a reminder to attend regular screening (control), (ii) an offer to order a self-sampling kit (opt-in) for HPV testing or (iii) a self-sampling kit unsolicited (send-to-all) for HPV testing. RESULTS: Total participation was 4.8%, 17.0% and 27.7% among control, opt-in and send-to-all (P < 0.0001; participation difference (%) send-to-all vs. control: 22.9 (95%CI: 20.7, 25.2); opt-in vs. control: 12.3 (95%CI: 10.3, 14.2); send-to-all vs. opt-in: 10.7 (95% CI: 8.0, 13.3)). High-risk HPV was detected in 11.5% of self-samples and 9.2% of clinician-collected samples (P = 0.40). Most women (92.5%) who returned a positive self-sample attended the clinic for triage testing. Of the 933 women screened, 33 (3.5%) had CIN2 + (1.1%, 3.7%, 3.8% among control, opt-in, and send-to-all, respectively), and 11 (1.2%) had cervical cancer (0%, 1.2%, 1.3% among control, opt-in, send-to-all, respectively). CONCLUSION: Opt-in and send-to-all self-sampling increased screening participation among long-term, higher-risk non-attenders. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03873376.