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AIMS: The optimal sampling methods for detecting human papillomavirus (HPV) in male genital sites remain unclear. This study aimed to assess the performance, acceptability, and comfort of two sampling techniques for male genital HPV detection. METHODS AND RESULTS: A total of 490 men aged 18-45 were randomly assigned in a 1:1 ratio to undergo either the rub-brush (nail file followed by swab) or brush-only method (swab only) for sampling at external genitalia sites (PGS) and perineum/perianal (PA) sites. HPV distribution, specimen validity (ß-globin as a quality reference), and participant acceptability and comfort were evaluated between the two sampling methods. The brush-only method demonstrated non-inferiority in detecting 14 high-risk HPV types (16/18/31/33/35/39/45/51/52/56/58/59/66/68) compared to the rub-brush method in both PGS (18.9% vs. 16.9%) and PA (10.5% vs. 11.9%). Although no significant differences were observed in positive rates for other HPV types, the brush-only method had a significantly higher invalid rate in PA (8.5% vs. 1.5%). Approximately 85.0% of participants reported good acceptability and comfort with both sampling methods, regardless of anatomical sites. CONCLUSIONS: This study suggests comparable performance, acceptability and comfort between the two sampling techniques for HPV detection. However, the rub-brush method may offer an advantage in higher sample validity.
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Papillomaviridae , Infecciones por Papillomavirus , Manejo de Especímenes , Humanos , Masculino , Adulto , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Manejo de Especímenes/métodos , Persona de Mediana Edad , Adulto Joven , Papillomaviridae/aislamiento & purificación , Adolescente , Genitales Masculinos/virologíaRESUMEN
OBJECTIVE: To assess the clinical values of extended human papillomavirus (HPV) genotyping in triage of high-risk HPV-positive women, focusing on the trade-off between cervical precancer detections and colposcopy referrals. METHODS: A bivariate random-effects model was used to estimate the diagnostic accuracy of primary HPV screening with following triage strategies to detect cervical precancers: (i) partial genotyping for HPV16/18 combined with cytological testing at atypical squamous cells of undetermined significance threshold (used as the comparator), (ii) genotyping for HPV16/18/58/52, (iii) genotyping for HPV16/18/58/52/33, (iv) genotyping for HPV16/18/58/33/31, (v) genotyping for HPV16/18/58/52/33/31, and (vi) genotyping for HPV16/18/58/52/33/31/39/51. Internal risk benchmarks for clinical management were used to evaluate the risk stratification of each triage strategy. RESULTS: A total of 16,982 women (mean age 46.1 years, range 17-69) were included in this analysis. For CIN3+ detection, triage with HPV16/18/58/33/31 genotyping achieved lower positivity (6.85% vs. 7.35%, p = 0.001), while maintaining similar sensitivity (91.35% vs. 96.42%, p = 0.32) and specificity (94.09% vs. 93.67%, p = 0.56) compared with the comparator strategy. Similar patterns were observed for CIN2+ detection. Women with a positive HPV16/18/58/33/31 genotyping test had high enough risk for CIN3+ for colposcopy referral, while the risk for women with a negative test was below the 1-year return decision threshold according to internal benchmarks. CONCLUSIONS: Our findings suggested extended HPV genotyping is of potential to be used as a triage technique integrated into HPV-based cervical cancer screening, leading to reduced need for colposcopy referral while maintaining similar disease detection and efficient risk stratification.
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Detección Precoz del Cáncer , Genotipo , Infecciones por Papillomavirus , Triaje , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Detección Precoz del Cáncer/métodos , Adulto , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Persona de Mediana Edad , Triaje/métodos , China/epidemiología , Adolescente , Adulto Joven , Colposcopía , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Anciano , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/aislamiento & purificación , Sensibilidad y Especificidad , Virus del Papiloma HumanoRESUMEN
PURPOSE: To evaluate the prognostic value of peripheral lymphocyte count (PLC) in the breast cancer patients after breast-conserving surgery (BCS) with radiotherapy (RT). METHODS AND MATERIALS: This post hoc analysis was performed using data of 628 patients from a phase III, randomized controlled trial comparing hypofractionated RT (HFRT) with conventional fractionated RT (CFRT) after BCS. PLCs were obtained before, during, and after RT until the 1-year follow-up. The optimal cut-off PLCs were determined using the maxstat package in R. Survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. RESULTS: A total of 275 (46.1 %) patients developed lymphopenia during RT, among them, 17 (2.8 %) had grade 3 lymphopenia and no one developed grade 4 lymphopenia. With a median follow-up of 110.8 months, patients with pre-RT PLCs of < 1.77 × 109/L had a significantly lower 10-year breast cancer-specific survival (BCSS) rate (P = 0.013) and overall survival (OS) rate (P = 0.026). Patients with a nadir PLC of < 1.35 × 109/L had a significantly poorer 10-year OS rate (P = 0.048). Multivariate analysis showed that a pre-RT PLC of < 1.77 × 109/L was an independent factor influencing BCSS and OS, while the effect of the nadir PLC did not remain significant. Neither PLC nor lymphopenia recovery at post-RT 1, 3, and 6 months and 1 year was associated with survival. CONCLUSIONS: Radiation-induced lymphopenia in patients with breast cancer after BCS tends to be mild. The lower pre-RT PLC predicted poorer survival.
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Neoplasias de la Mama , Mastectomía Segmentaria , Humanos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Femenino , Persona de Mediana Edad , Pronóstico , Anciano , Recuento de Linfocitos , Adulto , Linfopenia/etiología , Radioterapia Adyuvante , Tasa de Supervivencia , LinfocitosRESUMEN
Females with existing high-risk HPV (HR-HPV) infections remain at risk of subsequent multiple or recurrent infections, on which benefit from HPV vaccines was under-reported. We pooled individual-level data from four large-scale, RCTs of AS04-HPV-16/18 vaccine to evaluate efficacy and immunogenicity in females DNA-positive to any HR-HPV types at first vaccination. Females receiving the AS04-HPV-16/18 vaccine in the original RCTs constituted the vaccine group in the present study, while those unvaccinated served as the control group. Vaccine efficacy (VE) against new infections and associated cervical intraepithelial neoplasia (CIN) 2+ in females DNA-negative to the considered HR-HPV type but positive to any other HR-HPV types, VE against reinfections in females DNA-positive to the considered HR-HPV type but cleared naturally during later follow-up, and levels of anti-HPV-16/18 IgG were assessed. Our final analyses included 5137 females (vaccine group = 2532, control group = 2605). The median follow-up time was 47.88 months (IQR: 45.72-50.04). For the prevention of precancerous lesions related to the non-infected HR-HPV types at baseline, VE against HPV-16/18 related CIN 2+ was 82.70% (95% CI: 63.70-93.00%). For the prevention of reinfections related to the infected HR-HPV types following natural clearance, VE against HPV-16/18 12MPI was non-significant (p > .05), albeit robust immunity persisted for at least 48 months. Females with existing HR-HPV infections at first vaccination still benefit from vaccination in preventing precancers related to the non-infected types at baseline. VE against reinfections related to the infected types following natural clearance remains to be further investigated.
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Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Papillomavirus Humano 16 , Vacunas contra Papillomavirus/uso terapéutico , Reinfección/complicaciones , Papillomavirus Humano 18 , Vacunación , ADNRESUMEN
The human papillomavirus (HPV) vaccine is the first vaccine developed specifically targeting the prevention of cervical cancer. For more than 15 years, China has expedited a series of efforts on research and development of the domestically manufactured HPV vaccines, producing local population-based evidence, promoting free HPV vaccination from pilots, and launching action plans to tackle barriers in the scale-up of HPV vaccination. To further roll out the HPV vaccination program in China, several challenges should be addressed to support the steps forward. The availability of more locally manufactured HPV vaccines, pricing negotiation and local evidence supporting the efficacy of one-dose schedule would greatly alleviate the continued supply and financial constraints in China. Meanwhile, more attention should be paid to girls living in low-resource areas and males to ensure equal access to the HPV vaccination. Furthermore, linkage to secondary prevention and further real-world monitoring and evaluation are warranted to inform effective cervical cancer prevention strategies in the post-vaccine era.
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Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Masculino , Humanos , Virus del Papiloma Humano , Infecciones por Papillomavirus/prevención & control , Neoplasias del Cuello Uterino/prevención & control , Vacunación , ChinaRESUMEN
Background: Current uptake of HPV vaccination and screening in China is far below World Health Organization 2030 targets for cervical cancer elimination. We quantified health and economic losses of delaying large-scale HPV vaccination and screening implementation in China. Methods: We used a previously validated transmission model to project lifetime health benefits, costs, effectiveness, and timeline for cervical cancer elimination of alternative scenarios, including combining HPV vaccination initiated from 2022 to 2030 with screening in different modalities and coverage increase rates, as well as screening alone. All women living or projected to be born in China during 2022-2100 were considered. We employed a societal perspective. Findings: Regardless of vaccine type, immediate large-scale vaccination initiated in 2022 and achieving 70% coverage of HPV-based screening in 2030 (no-delay scenario) would be the least costly and most effective. Compared with the no-delay scenario, delaying vaccination by eight years would result in 434,000-543,000 additional cervical cancer cases, 138,000-178,000 deaths, and $2863-4437 million costs, and delay elimination by 9-10 years. Even with immediate vaccination, the gradual scale-up of LBC-based screening to 70% coverage in 2070 would result in 2,530,000-3,060,000 additional cases, 909,000-1,040,000 deaths, and $5098-5714 million costs compared with no-delay scenario, and could not achieve elimination if domestic 2vHPV or 4vHPV vaccines are used (4.09-4.21 cases per 100,000 woman in 2100). Interpretation: Delaying large-scale HPV vaccination and/or high-performance screening implementation has detrimental consequences for cervical cancer morbidity, mortality, and expenditure. These findings should spur health authorities to expedite large-scale vaccine rollout and improve screening. Funding: Bill & Melinda Gates Foundation (INV-031449 and INV-003174) and CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-004).
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BACKGROUND: Women with breast cancer and improved survival face some specific quality of life (QOL) issues. Electronic health (eHealth) is a useful tool aiming to enhance health services. However, evidence remains controversial about the effect of eHealth on QOL in women with breast cancer. Another unstudied factor is the effect on specific QOL functional domains. Therefore, we undertook a meta-analysis about whether eHealth could improve the overall and specific functional domains of QOL in women with breast cancer. METHODS: PubMed, Cochrane Library, EMBASE, and Web of Science were searched to identify appropriate randomized clinical trials from database inception to March 23, 2022. The standard mean difference (SMD) served as the effect size and the DerSimonian-Laird random effects model was constructed for meta-analysis. Subgroup analyses were conducted according to different participant, intervention, and assessment scale characteristics. RESULTS: We initially identified 1954 articles excluding duplicates and ultimately included 13 of them involving 1448 patients. The meta-analysis revealed that the eHealth group had significantly higher QOL (SMD 0.27, 95% confidence interval [95% CI] 0.13-0.40, p < 0.0001) than the usual care group. Additionally, although not statistically significant, eHealth tended to improve the physical (SMD 2.91, 95% CI -1.18 to 6.99, p = 0.16), cognitive (0.20 [-0.04, 0.43], p = 0.10), social (0.24 [-0.00, 0.49], p = 0.05), role (0.11 [0.10, 0.32], p = 0.32), and emotional (0.18 [0.08, 0.44], p = 0.18) domains of QOL. Overall, consistent benefits were observed in both the subgroup and pooled estimates. CONCLUSIONS: eHealth is superior to usual care in women with breast cancer for improved QOL. Implications for clinical practice should be discussed based on subgroup analysis results. Further confirmation is needed for the effect of different eHealth patterns on specific domains of QOL, which would help improve specific health issues of the target population.
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Neoplasias de la Mama , Telemedicina , Humanos , Femenino , Calidad de Vida/psicología , Neoplasias de la Mama/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , ElectrónicaRESUMEN
BACKGROUND: Self-sampling HPV test and thermal ablation are effective tools to increase screening coverage and treatment compliance for accelerating cervical cancer elimination. We assessed the cost-effectiveness of their combined strategies to inform accessible, affordable, and acceptable cervical cancer prevention strategies. METHODS: We developed a hybrid model to evaluate costs, health outcomes, and incremental cost-effectiveness ratios (ICER) of six screen-and-treat strategies combining HPV testing (self-sampling or physician-sampling), triage modalities (HPV genotyping, colposcopy or none) and thermal ablation, from a societal perspective. A designated initial cohort of 100,000 females born in 2015 was considered. Strategies with an ICER less than the Chinese gross domestic product (GDP) per capita ($10,350) were considered highly cost-effective. RESULTS: Compared with current strategies in China (physician-HPV with genotype or cytology triage), all screen-and-treat strategies are cost-effective and self-HPV without triage is optimal with the most incremental quality-adjusted life-years (QALYs) gained (220 to 440) in rural and urban China. Each screen-and-treat strategy based on self-collected samples is cost-saving compared with current strategies (-$818,430 to -$3540) whereas more costs are incurred using physician-collected samples compared with current physician-HPV with genotype triage (+$20,840 to +$182,840). For screen-and-treat strategies without triage, more costs (+$9404 to +$380,217) would be invested in the screening and treatment of precancerous lesions rather than the cancer treatment compared with the current screening strategies. Notably, however, more than 81.6% of HPV-positive women would be overtreated. If triaged with HPV 7 types or HPV16/18 genotypes, 79.1% or 67.2% (respectively) of HPV-positive women would be overtreated with fewer cancer cases avoided (19 cases or 69 cases). CONCLUSIONS: Screen-and-treat strategy using self-sampling HPV test linked to thermal ablation could be the most cost-effective for cervical cancer prevention in China. Additional triage with quality-assured performance could reduce overtreatment and remains highly cost-effective compared with current strategies.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Niño , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/diagnóstico , Análisis Costo-Beneficio , Papillomavirus Humano 16/genética , Infecciones por Papillomavirus/diagnóstico , Papillomavirus Humano 18/genética , Tamizaje Masivo , Detección Precoz del CáncerRESUMEN
OBJECTIVES: This study aimed to investigate whether a deep learning (DL) model based on preoperative MR images of primary tumors can predict lymph node metastasis (LNM) in patients with stage T1-2 rectal cancer. METHODS: In this retrospective study, patients with stage T1-2 rectal cancer who underwent preoperative MRI between October 2013 and March 2021 were included and assigned to the training, validation, and test sets. Four two-dimensional and three-dimensional (3D) residual networks (ResNet18, ResNet50, ResNet101, and ResNet152) were trained and tested on T2-weighted images to identify patients with LNM. Three radiologists independently assessed LN status on MRI, and diagnostic outcomes were compared with the DL model. Predictive performance was assessed with AUC and compared using the Delong method. RESULTS: In total, 611 patients were evaluated (444 training, 81 validation, and 86 test). The AUCs of the eight DL models ranged from 0.80 (95% confidence interval [CI]: 0.75, 0.85) to 0.89 (95% CI: 0.85, 0.92) in the training set and from 0.77 (95% CI: 0.62, 0.92) to 0.89 (95% CI: 0.76, 1.00) in the validation set. The ResNet101 model based on 3D network architecture achieved the best performance in predicting LNM in the test set, with an AUC of 0.79 (95% CI: 0.70, 0.89) that was significantly greater than that of the pooled readers (AUC, 0.54 [95% CI: 0.48, 0.60]; p < 0.001). CONCLUSION: The DL model based on preoperative MR images of primary tumors outperformed radiologists in predicting LNM in patients with stage T1-2 rectal cancer. KEY POINTS: ⢠Deep learning (DL) models with different network frameworks showed different diagnostic performance for predicting lymph node metastasis (LNM) in patients with stage T1-2 rectal cancer. ⢠The ResNet101 model based on 3D network architecture achieved the best performance in predicting LNM in the test set. ⢠The DL model based on preoperative MR images outperformed radiologists in predicting LNM in patients with stage T1-2 rectal cancer.
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Aprendizaje Profundo , Neoplasias del Recto , Humanos , Metástasis Linfática/patología , Estudios Retrospectivos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Imagen por Resonancia Magnética/métodos , Neoplasias del Recto/patologíaRESUMEN
BACKGROUND: There are no studies extrapolating the incidence and mortality of cervical cancer in China by comparing incidence and deaths pattern between geographic and age groups. METHODS: We applied age-period-cohort models to assess region-level trends in incidence and mortality from 2006 to 2016, with piecewise linear regression in a Bayesian framework to predict these trends to 2030. RESULTS: Between 2006 and 2016, age-standardized incidence rates (ASIR) for females aged 15 to 84 years increased by 3.7% (95% confidence interval, 3.1%-4.3%) annually from 11.01 to 16.41 per 100,000 females in China. In the 25 to 39 age groups, the incidence rates decreased in urban regions and inversely increased in rural regions. The age-standardized mortality rates (ASMR) increased from 3.18 to 4.83, with annual increases of about 3.6% (1.5%-5.8%). From 2017 to 2030, the ASIR is expected to increase from 17.13 (15.91-18.46) to 23.22 (20.02-27.01) by 2.5% per year (P < 0.05). Meanwhile, the average age at diagnosis is predicted to grow from 53.1 to 60.5 years. In the 15 to 54 age groups, the incidence rates decreased in urban regions but increased in rural regions. The ASMR is expected to increase consistently from 4.82 (4.38-5.31) to 9.13 (7.35-11.39) by 5.0% per year (P < 0.05). CONCLUSIONS: Cervical cancer incidence and mortality rates are projected to increase in China. In addition, the urban-rural incidence gap is estimated to widen further among young women. IMPACT: Cervical cancer prevention should consider the trend and diversity in incidence patterns between urban and rural regions.
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Neoplasias del Cuello Uterino , Humanos , Femenino , Persona de Mediana Edad , Neoplasias del Cuello Uterino/epidemiología , Incidencia , Teorema de Bayes , Población Urbana , China/epidemiología , Estudios de Cohortes , MortalidadRESUMEN
Although urine-based human papillomavirus (HPV) detection is promising in cervical cancer screening, it has not yet been well-developed. Women aged 30-65 were invited to participate in the current study to provide one urine and two paired vaginal samples. Urine was detected by polymerase chain reaction (PCR)-based HPV test (urine-based HPV test). Two vaginal samples were tested by careHPV and GenPlex® HPV genotyping assay, respectively. Women with vaginal HPV positive were called back for colposcopy and biopsied if clinically indicated. The consistency was 79.0% (κ = 0.563) and 80.5% (κ = 0.605) between the urine-based HPV test, careHPV test, and GenPlex® HPV genotyping assay. Against CIN2 detection, the careHPV test showed 77.4% sensitivity, and 71.0% specificity, while the GenPlex® HPV genotyping assay had a sensitivity of 100% and a specificity of 58.7%. For urine-based HPV test, the corresponding rates were 96.8% and 58.7%. Moreover, no significant differences were observed between the urine-based HPV test and careHPV test (p = 0.3395) and GenPlex® HPV genotyping assay (p = 0.338). The newly developed urine-based HPV test demonstrated acceptable consistency and comparable clinical performance with referenced HPV tests for vaginal samples. Therefore, urine-based HPV detection could be a useful alternative for women with difficulties to access cervical cancer screening.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Sensibilidad y Especificidad , Detección Precoz del Cáncer , Infecciones por Papillomavirus/diagnóstico , ADN Viral/análisis , Papillomaviridae/genética , Virus del Papiloma Humano , China/epidemiología , Tamizaje MasivoRESUMEN
The appropriate management strategies for BI-RADS category 4a lesions among handheld ultrasound (HHUS) remain a matter of debate. We aimed to explore the role of automated breast ultrasound (ABUS) or the second-look mammography (MAM) adjunct to ultrasound (US) of 4a masses to reduce unnecessary biopsies. Women aged 30 to 69 underwent HHUS and ABUS from 2016 to 2017 at five high-level hospitals in China, with those aged 40 or older also accepting MAM. Logistic regression analysis assessed image variables correlated with false-positive lesions in US category 4a. Unnecessary biopsies, invasive cancer (IC) yields, and diagnostic performance among different biopsy thresholds were compared. A total of 1946 women (44.9 ± 9.8 years) were eligible for analysis. The false-positive rate of category 4a in ABUS was almost 65.81% (77/117), which was similar to HHUS (67.55%; 127/188). Orientation, architectural distortion, and duct change were independent factors associated with the false-positive lesions in 4a of HHUS, whereas postmenopausal, calcification, and architectural distortion were significant features of ABUS (all p < 0.05). For HHUS, both unnecessary biopsy rate and IC yields were significantly reduced when changing biopsy thresholds by adding MAM for US 4a in the total population (scenario #1:BI-RADS 3, 4, and 5; scenario #2: BI-RADS 4 and 5) compared with the current scenario (all p < 0.05). Notably, scenario #1 reduced false-positive biopsies without affecting IC yields when compared to the current scenario for ABUS (p < 0.001; p = 0.125). The higher unnecessary biopsy rate of category 4a by ABUS was similar to HHUS. However, the second-look MAM adjunct to ABUS has the potential to safely reduce false-positive biopsies compared with HHUS.
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Mamografía , Ultrasonografía Mamaria , Femenino , Humanos , Ultrasonografía Mamaria/métodos , Sensibilidad y Especificidad , China , Biopsia , HospitalesRESUMEN
Background: A key barrier to cervical cancer elimination in China is low human papillomavirus (HPV) vaccine uptake, which is limited by supply constraints, high prices, and restriction to two/three-dose schedule. We explored optimal vaccination strategies for maximizing health and economic benefits accommodated to different supply and dose schedules. Methods: We evaluated different HPV vaccine strategies under 4 scenarios with different assumptions about vaccine availability and dose schedules. Each strategy involved different vaccine types, target ages, and modes of delivery. We used a previously validated transmission model to assess the health impact (cervical cancer cases averted), efficiency (number of doses needed to be given to prevent one case of cervical cancer [NND]), and value for money (incremental cost-effectiveness ratio [ICER] and return on investment [ROI]) of different strategies in Chinese females over a 100-year time horizon. All costs are expressed in 2021 dollars. We adopted a societal perspective and discounted quality-adjusted life-years (QALYs), costs and benefits by 3% annually for cost-effectiveness analysis and ROI calculation. Findings: In a supply-constrained and on-label use scenario, compared with no vaccination, two-dose routine vaccination of 14-year-olds would be the optimal, cost-saving strategy for a future national program (NNDs: 150-220, net cost saving: $15 164 million-$22 034 million, ROIs: 7-14, depending on vaccine type). If the one-dose schedule recommended by WHO is permitted in China, then reallocating the second dose from the routine cohorts to add a catch-up vaccination at 20-year-olds would be the most efficient strategy (NNDs: 73-107), and would be cost-saving compared with routine one-dose vaccination only (net cost saving: $4127 million-$6035 million, ROIs: 19-37). When supply constraints are lifted, scaling up vaccination in older females to 26 years could further expand the health benefits and still be cost-saving compared to maintaining the optimal vaccination strategy in the supply-constrained context. Interpretation: Our study provides timely evidence for the current and future HPV vaccination strategy planning in China, and may also be of value to other countries with supply and dose restrictions. Funding: Bill & Melinda Gates Foundation; CAMS Innovation Fund for Medical Sciences (CIFMS).
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OBJECTIVE: To address the value of visual inspection where HPV-based screening is not yet available, we evaluated the real-world effectiveness of visual inspection with acetic acid (VIA) and with Lugol's iodine (VILI) as a primary screening method for cervical cancer in rural China. METHODS: A total of 206 133 women aged 30-59 years received two rounds of VIA/VILI screening for cervical cancer in 2006-2010. Women with positive screening results underwent colposcopy and direct biopsy, and were treated if cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed. Clinical effectiveness of VIA/VILI was evaluated by process and outcome measures. RESULTS: The VIA/VILI positivity rate, biopsy rate and detection rate of CIN2+ in the second round were significantly lower than in the first round. The 2-year cumulative detection rate of CIN2+ varied from 0.53% to 0.90% among the four cohorts initiated in 2006, 2007, 2008, and 2009. The first round of screening detected 60%-83% of CIN2, 70%-86% of CIN3, and 88%-100% of cervical cancer. Over 92% of CIN2+ were found at the early stage. CONCLUSION: Multiple rounds of visual inspection with continuous training and quality assurance could act as a temporary substitutional screening method for cervical cancer in resource-restricted settings.
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Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Ácido Acético , Detección Precoz del Cáncer/métodos , Displasia del Cuello del Útero/diagnóstico , Yoduros , Tamizaje Masivo/métodosRESUMEN
INTRODUCTION: The pivotal efficacy study assessed efficacy and safety of GSK's AS04-HPV-16/18 vaccine in Chinese women aged 18-25 years up to 6 years. The present extension study, performed 4 years later, offered AS04-HPV-16/18 vaccination to placebo recipients. Vaccine safety and its long-term protective effect were assessed at Year 10. METHODS: All 6051 women who received AS04-HPV-16/18 or the placebo during the initial study (NCT00779766) were invited to phase III/IV, open-label, partially controlled extension Year 10 study (NCT03629886). Placebo recipients were offered three-dose AS04-HPV-16/18 vaccination and followed up over 12 months to assess the safety. Cervical samples from all women were examined. Vaccine efficacy (VE) against incident infections and cytological lesions associated with HPV-16/18 and other oncogenic types was assessed as exploratory objective. RESULTS: Among 3537 women (out of 6051) enrolled in the extension study, 1791 women (mean age 32.7 years; standard deviation 1.8 years) received AS04-HPV-16/18 and reported no serious adverse events, potential immune-mediated diseases, or adverse pregnancy outcomes related to vaccination. Among 6051 women, VE against incident HPV-16, -18, and -16/18 infections up to Year 10 was 82.8% (95% confidence interval: 72.5-89.7), 79.8% (64.5-89.2), and 80.8% (72.4-87.0), respectively. VE against HPV-16/18 ASC-US+, CIN1+, and CIN2+ was 92.7% (82.2-97.7), 94.8% (67.4-99.9), and 90.5% (34.6-99.8), respectively. CONCLUSION: AS04-HPV-16/18 vaccine showed an acceptable safety profile in Chinese women vaccinated at age 26 years or above, and a long-term protection similar to other efficacy trials worldwide.
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Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Adolescente , Adulto , Femenino , Humanos , Embarazo , Adulto Joven , Pueblos del Este de Asia , Estudios de Seguimiento , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/efectos adversos , Vacunas contra Papillomavirus/uso terapéutico , Neoplasias del Cuello Uterino/prevención & controlRESUMEN
Objective: Cervical squamous intraepithelial lesion (SIL) and cervical cancer are major threats to females' health and life in China, and we aimed to estimate the economic burden associated with their diagnosis and treatment. Methods: A nationwide multicenter, cross-sectional, hospital-based survey was conducted in 26 qualified hospitals across seven administrative regions of China. We investigated females who had been pathologically diagnosed with SIL and cervical cancer, and included five disease courses ("diagnosis", "initial treatment", "chemoradiotherapy", "follow-up" and "recurrence/progression/metastasis") to estimate the total costs. The median and interquartile range (IQR) of total costs (including direct medical, direct non-medical, and indirect costs), reimbursement rate by medical insurance, and catastrophic health expenditures in every clinical stage were calculated. Results: A total of 3,471 patients in different clinical stages were analyzed, including low-grade SIL (LSIL) (n=549), high-grade SIL (HSIL) (n=803), cervical cancer stage IA (n=226), IB (n=610), IIA (n=487), IIB (n=282), III (n=452) and IV (n=62). In urban areas, the estimated total costs of LSIL and HSIL were [Formula: see text]1,637.7 (IQR: [Formula: see text]956.4-[Formula: see text]2,669.2) and [Formula: see text]2,467.1 (IQR: [Formula: see text]1,579.1-[Formula: see text]3,762.3), while in rural areas the costs were [Formula: see text]459.0 (IQR: [Formula: see text]167.7-[Formula: see text]1,330.3) and [Formula: see text]1,230.5 (IQR: [Formula: see text]560.6-[Formula: see text]2,104.5), respectively. For patients with cervical cancer stage IA, IB, IIA, IIB, and III-IV, the total costs were [Formula: see text]15,034.9 (IQR: [Formula: see text]11,083.4-[Formula: see text]21,632.4), [Formula: see text]19,438.6 (IQR: [Formula: see text]14,060.0-[Formula: see text]26,505.9), [Formula: see text]22,968.8 (IQR: [Formula: see text]16,068.8-[Formula: see text]34,615.9), [Formula: see text]26,936.0 (IQR: [Formula: see text]18,176.6-[Formula: see text]41,386.0) and [Formula: see text]27,332.6 (IQR: [Formula: see text]17,538.7-[Formula: see text]44,897.0), respectively. Medical insurance covered 43%-55% of direct medical costs for cervical cancer patients, while the coverage for SIL patients was 19%-43%. For most cervical cancer patients, the expense was catastrophic, and the extent of catastrophic health expenditure was about twice large for rural patients than that for urban patients in each stage. Conclusions: The economic burden of SIL and cervical cancer in China is substantial, with a significant proportion of the costs being avoidable for patients with LSIL. Even for those with medical insurance, catastrophic health expenditures are also a major concern for patients with cervical cancer, particularly for those living in rural areas.
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BACKGROUND: To investigate the differences in HPV genotypes and clinical indicators between cervical squamous cell carcinoma and adenocarcinoma and to identify independent predictors for differentiating cervical squamous cell carcinoma and adenocarcinoma. METHODS: A total of 319 patients with cervical cancer, including 238 patients with squamous cell carcinoma and 81 patients with adenocarcinoma, were retrospectively analysed. The clinical characteristics and laboratory indicators, including HPV genotypes, SCCAg, CA125, CA19-9, CYFRA 21-1 and parity, were analysed by univariate and multivariate analyses, and a classification model for cervical squamous cell carcinoma and adenocarcinoma was established. The model was validated in 96 patients with cervical cancer. RESULTS: There were significant differences in SCCAg, CA125, CA19-9, CYFRA 21-1, HPV genotypes and clinical symptoms between cervical squamous cell carcinoma and adenocarcinoma (P < 0.05). Logistic regression analysis showed that SCCAg and HPV genotypes (high risk) were independent predictors for differentiating cervical squamous cell carcinoma from adenocarcinoma. The AUC value of the established classification model was 0.854 (95% CI: 0.804-0.904). The accuracy, sensitivity and specificity of the model were 0.846, 0.691 and 0.899, respectively. The classification accuracy was 0.823 when the model was verified. CONCLUSION: The histological type of cervical cancer patients with persistent infection of high-risk HPV subtypes and low serum SCCAg levels was more prone to being adenocarcinoma. When the above independent predictors occur, the occurrence and development of cervical adenocarcinoma should be anticipated, and early active intervention treatment should be used to improve the prognosis and survival of patients.
Asunto(s)
Adenocarcinoma , Carcinoma de Células Escamosas , Papillomaviridae , Infecciones por Papillomavirus , Serpinas , Neoplasias del Cuello Uterino , Antígenos de Neoplasias , Antígeno CA-19-9 , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Femenino , Genotipo , Humanos , Queratina-19 , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virologíaRESUMEN
INTRODUCTION: Human papillomavirus (HPV) vaccines protect against incident HPV infections, which cause cervical cancer. OBJECTIVES: We estimated the prevalence and incidence of HPV infections in young adult women to understand the impact of an HPV vaccination programme in this population. METHODS: We collected cervical specimens from 6322 unvaccinated women, aged 18-37 years, who participated in the Costa Rica Vaccine Trial and its long-term follow-up. Women were followed for (median) 4.8 years and had (median) 4.0 study visits. Cervical specimens were tested for the presence/absence of 25 HPV genotypes. For each age band, we estimated the percentage of women with 1+ prevalent or 1+ incident HPV infections using generalised estimating equations. We also estimated the prevalence and incidence of HPV as a function of time since first sexual intercourse (FSI). RESULTS: The model estimated HPV incident infections peaked at 28.0% (95% CI 25.3% to 30.9%) at age 20 years then steadily declined to 11.8% (95% CI 7.6% to 17.8%) at age 37 years. Incident oncogenic HPV infections (HPV16/18/31/33/35/39/45/51/52/56/58/59) peaked and then declined from 20.3% (95% CI 17.9% to 22.9%) to 7.7% (95% CI 4.4% to 13.1%); HPV16/18 declined from 6.4% (95% CI 5.1% to 8.1%) to 1.1% (95% CI 0.33% to 3.6%) and HPV31/33/45/52/58 declined from 11.0% (95% CI 9.3% to 13.1%) to 4.5% (95% CI 2.2% to 8.9%) over the same ages. The percentage of women with 1+ incident HPV of any, oncogenic, non-oncogenic and vaccine-preventable (HPV16/18, HPV31/33/45, HPV31/33/45/52/58, and HPV6/11) types peaked <1 year after FSI and steadily declined with increasing time since FSI (p for trends <0.001). We observed similar patterns for model estimated HPV prevalences. CONCLUSION: Young adult women may benefit from HPV vaccination if newly acquired vaccine-preventable oncogenic infections lead to cervical precancer and cancer. HPV vaccination targeting this population may provide additional opportunities for primary prevention. TRIAL REGISTRATION NUMBER: NCT00128661.
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BACKGROUND: In women vaccinated against human papillomavirus (HPV), reductions in cervical disease and related procedures results in more women having intact transformation zones, potentially increasing the risk of cervical lesions caused by non-vaccine-preventable HPV types, a phenomenon termed clinical unmasking. We aimed to evaluate HPV vaccine efficacy against cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and cervical intraepithelial neoplasia grade 3 or worse (CIN3+) attributed to non-preventable HPV types in the long-term follow-up phase of the Costa Rica HPV Vaccine Trial (CVT). METHODS: CVT was a randomised, double-blind, community-based trial done in Costa Rica. Eligible participants were women aged 18-25 years who were in general good health. Participants were randomly assigned (1:1) to receive an HPV 16 and 18 AS04-adjuvanted vaccine or control hepatitis A vaccine, using a blocked randomisation method (permuted block sizes of 14, 16, and 18). Vaccines in both groups were administered intramuscularly with 0·5 mL doses at 0, 1, and 6 months. Masking of vaccine allocation was maintained throughout the 4-year randomised trial phase, after which participants in the hepatitis A virus vaccine control group were provided the HPV vaccine and exited the study; a screening-only, unvaccinated control group was enrolled. The unvaccinated control group and HPV vaccine group were followed up for 7 years, during which treatment allocation was not masked. One of the prespecified primary endpoints for the long-term follow-up phase was precancers associated with HPV types not prevented by the vaccine, defined as histologically confirmed incident CIN2+ events or CIN3+ events attributed to any HPV type except HPV 16, 18, 31, 33, and 45. Our primary analytical period was years 7-11. Primary analyses were in all participants with at least one follow-up visit and excluded participants with a previous endpoint (ie, modified intention-to-treat cohort). Safety endpoints have been reported elsewhere. This trial is registered with ClinicalTrials.gov, NCT00128661 and NCT00867464. The randomised, masked trial phase is completed; an unmasked subset of women in the HPV-vaccinated group is under active investigation. FINDINGS: Between June 28, 2004, and Dec 21, 2005, 7466 participants were enrolled (HPV vaccine group n=3727 and hepatitis A virus vaccine control group n=3739). Between March 30, 2009, and July 5, 2012, 2836 women enrolled in the new unvaccinated control group. The primary analytical cohort (years 7 to 11) included 2767 participants in the HPV vaccine group and 2563 in the unvaccinated group for the CIN2+ events endpoint assessment and 2826 participants in the HPV vaccine group and 2592 in the unvaccinated control group for the CIN3+ events endpoint assessment. Median follow-up during years 7 to 11 for women included for the CIN2+ events analysis was 52·8 months (IQR 44·0 to 60·7) for the HPV vaccine group and 49·8 months (42·0 to 56·9) for the unvaccinated control group. During years 7 to 11, clinical unmasking was observed with a negative vaccine efficacy against CIN2+ events attributed to non-preventable HPV types (-71·2% [95% CI -164·0 to -12·5]), with 9·2 (95% CI 2·1 to 15·6) additional CIN2+ events attributed to non-preventable HPV types per 1000 HPV-vaccinated participants versus HPV-unvaccinated participants. 27·0 (95% CI 14·2 to 39·9) fewer CIN2+ events irrespective of HPV type per 1000 vaccinated participants were observed during 11 years of follow-up. Vaccine efficacy against CIN3+ events attributed to non-preventable HPV types during years 7 to 11 was -135·0% (95% CI -329·8 to -33·5), with 8·3 (3·0 to 12·8) additional CIN3+ events attributed to non-preventable HPV types per 1000 vaccinated participants versus unvaccinated participants. INTERPRETATION: Higher rates of CIN2+ events and CIN3+ events due to non-preventable HPV types in vaccinated versus unvaccinated participants suggests clinical unmasking could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programmes in screened populations. Importantly, the net benefit of vaccination remains considerable; therefore, HPV vaccination should still be prioritised as primary prevention for cervical cancer. FUNDING: National Cancer Institute and National Institutes of Health Office of Research on Women's Health. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.
Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Lesiones Precancerosas , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Adolescente , Adulto , Costa Rica/epidemiología , Femenino , Estudios de Seguimiento , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Masculino , Papillomaviridae , Lesiones Precancerosas/prevención & control , Neoplasias del Cuello Uterino/patología , Vacunación , Adulto Joven , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/prevención & controlRESUMEN
BACKGROUND: We investigated the impact of human papillomavirus (HPV) vaccination on the performance of cytology-based and HPV-based screening for detection of cervical precancer among women vaccinated as young adults and reaching screening age. METHODS: A total of 4632 women aged 25-36 years from the Costa Rica HPV Vaccine Trial were included (2418 HPV-vaccinated as young adults and 2214 unvaccinated). We assessed the performance of cytology- and HPV-based cervical screening modalities in vaccinated and unvaccinated women to detect high-grade cervical precancers diagnosed over 4 years and the absolute risk of cumulative cervical precancers by screening results at entry. RESULTS: We detected 95 cervical intraepithelial neoplasia grade 3 or worse (52 in unvaccinated and 43 in vaccinated women). HPV16/18/31/33/45 was predominant (69%) among unvaccinated participants, and HPV35/52/58/39/51/56/59/66/68 predominated (65%) among vaccinated participants. Sensitivity and specificity of cervical screening approaches were comparable between women vaccinated as young adults and unvaccinated women. Colposcopy referral rates were lower in the vaccinated group for HPV-based screening modalities, but the positive predictive value was comparable between the 2 groups. CONCLUSIONS: Among women approaching screening ages, vaccinated as young adults, and with a history of intensive screening, the expected reduction in the positive predictive value of HPV testing, associated with dropping prevalence of HPV-associated lesions, was not observed. This is likely due to the presence of high-grade lesions associated with nonvaccine HPV types, which may be less likely to progress to cancer.