Modeling the potential impact of HPV vaccination on Hong Kong's cervical cancer burden

Background. Cervical cancer is a common female cancer in Hong Kong. Cervical screening has been used in detecting cervical lesions for several decades. Given that human papillomavirus (HPV) infection is the etiological cause of cervical cancer, highly efficacious HPV vaccines are recently developed for preventing against HPV infection. Hong Kong has a well-developed healthcare system but relatively high cervical cancer incidence compared to other developed countries partly due to its suboptimal cervical screening program. This highlights the significance to evaluate the potential of implementing organized HPV vaccination programs for further reducing cervical cancer burden on top of cervical screening in Hong Kong. Methods. Cross-sectional, population-based surveys were conducted to assess the acceptability of female adolescent HPV vaccination among girls from secondary schools in 2008 and among mothers of adolescent daughters in 2008 and 2012. Mathematical model with transmission dynamic and stochastic individual-based components was constructed to model the natural history of HPV infection and cervical cancer and thus to project the public health and economic impacts of organized female adolescent HPV vaccination programs in a societal perspective. The model used Markov Chain Monte Carlo algorithm to estimate natural history parameters of HPV infection and probabilistic sensitivity analysis to consider the uncertainty of costs and health utilities in the economic evaluation of organized HPV vaccination. Results. Reported vaccine uptake among11–18 year-old girls increased from 2.4% among schoolgirls in 2008 to 9.1% among daughters of interviewed mothers in 2012. Among interviewed mothers, 27.5% and 37.6% of them were willing to have their daughters vaccinated at market price in 2008 and 2012, respectively. The mathematical model projected that HPV prevalence decreased soon after mass HPV vaccination and vaccine-induced cervical cancer reduction became obvious after vaccination programs have been launched for 30 years. If HPV vaccinesprovided30-year protection, the median incremental cost-effectiveness ratio (ICER) of routine HPV vaccination programs for 12 year-old girls at 25–75% vaccination coverage was US$26,367–32,527 per quality-adjusted life-year (QALY). The median ICER was above US$48,000/QALY if adding 2-year catch-up program for13–18 year-old girls and above US$58,000/QALY if vaccines protect against HPV infection for only 15 years. Conclusions. This study presented the first evaluation of organized HPV vaccination programs in Hong Kong. If vaccine protection lasted for 30 years or longer, organized routine HPV vaccination for 12 year-old girls would potentially be a cost-effective add-on in substantially reducing cervical cancers and HPV-related diseases on top of cervical screening in Hong Kong at an ICER threshold of US$33,218/QALY. However, the current estimated vaccine uptake was unexpectedly low and vaccine acceptability was only moderate. The findings indicated the importance to devise efficient strategies in achieving high and universal coverage for maximizing the population-level benefits of HPV vaccination. Policymakers should consider integrating the organized HPV vaccination programs with existing infrastructures to promote higher acceptability, to translate willingness to vaccinate to actual uptake, to assess population effectiveness, and to monitor safety issue and potential replacement effect of non-vaccine targeted HPV types following mass vaccination.published_or_final_versionPublic HealthDoctoralDoctor of Philosoph

Overall Survival Benefits of First-Line Treatments for Asian Patients with Advanced Epidermal Growth Factor Receptor-Mutated NSCLC Harboring Exon 19 Deletion: A Systematic Review and Network Meta-Analysis

(1) Background: Randomized controlled trials (RCTs) have explored various primary treatments for individuals diagnosed as having later-stage epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer. Nevertheless, the extent to which such treatments are efficacious, particularly with regard to overall survival (OS) rates of patients from Asia with exon 19 deletion (19del), has yet to be clarified. (2) Methods: A systematic review and frequentist network meta-analysis were conducted by obtaining pertinent studies from PubMed/MEDLINE Ovid, Embase, Cochrane Library, and trial registries, as well as various other sources. RCTs in which two or multiple treatments in the primary setting for patients from Asia with EGFR 19del were compared were included. This research has been recorded in the Prospective Register of Systematic Reviews (CRD 42022320833). (3) Results: A total of 2715 patients from Asia participated in 18 trials in which 12 different treatments were administered, which included: EGFR tyrosine kinase inhibitors (TKIs) (osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib), pemetrexed-based chemotherapy, pemetrexed-free chemotherapy, and combination treatments (gefitinib plus apatinib, erlotinib plus ramucirumab, erlotinib plus bevacizumab, and gefitinib plus pemetrexed-based chemotherapy). Such treatments were not significantly beneficial in terms of OS for patients from Asia who had 19del. It was demonstrated that erlotinib plus bevacizumab, ramucirumab plus erlotinib, and osimertinib consistently yielded the greatest benefits regarding progression-free survival benefit (P-scores = 94%, 84%, and 80%, respectively). Combination treatments resulted in increased toxicity, particularly gefitinib plus apatinib and erlotinib plus bevacizumab, causing the highest prevalence of grade ≥ 3 adverse events. Icotinib and osimertinib had the fewest grade ≥ 3 adverse events. Specific treatments were associated with a wide range of toxicity levels. (4) Conclusions: In patients from Asia with 19del, both EGFR-TKIs and treatments in which therapies were combined exhibited no OS benefits in comparison with standard chemotherapy treatments. Additional research is required to study TKIs’ resistance mechanisms and possible combined approaches for individuals harboring this common mutation

Cost-Effectiveness of Intranasal Live-Attenuated Influenza Vaccine for Children: A Systematic Review

Introduction: The public health burden of seasonal influenza is significant, and influenza vaccination is the most effective preventive strategy. Nonetheless, the recommendation of influenza immunization in the pediatric population is still underrepresented. Our work aimed to assess the cost-effectiveness of pediatric influenza vaccination with the intranasal live-attenuated influenza vaccine (LAIV). Methods: We performed a systematic review of publications from PubMed/MEDLINE, Embase, and Scopus, covering the period from 1 January 2000 to 30 April 2022. We searched for economic evaluations that studied the impacts of LAIV among children or the pediatric population. Studies that considered incremental cost-effectiveness ratios (ICERs), in terms of cost per gain in life years, quality adjusted life years, or disability-adjusted life years, were covered. The Consensus Health Economic Criteria (CHEC) Extended Checklist was adopted to check the quality of the included studies. Results: Thirteen studies were included for the final review that were of good or excellent quality. The implementation of influenza vaccination with intranasal LAIV in the pediatric population was cost-effective when compared to the immunization strategies for the elderly and the high-risk groups alone or with no vaccination. The efficacy of LAIV for children, vaccination coverage, and the vaccine price were significant factors to the cost-effectiveness of influenza vaccination for children. Another significant contribution to the cost-effectiveness was the herd immunity arising from pediatric immunization against influenza. Conclusions: The implementation of influenza vaccination in the pediatric population with LAIV is cost-effective. Policymakers and health authorities may consider the evidence on the development of the pediatric influenza vaccination in their immunization schedules

“Fact or fiction?”: oral cavity cancer in nonsmoking, nonalcohol drinking patients as a distinct entity — scoping review

Oral cavity cancer is often described as a lifestyle-related malignancy due to its strong associations with habitual factors, including tobacco use, heavy alcohol consumption, and betel nut chewing. However, patients with no genetically predisposing conditions who do not indulge in these risk habits are still being encountered, albeit less commonly. The aim of this review is to summarize contemporaneous reports on these nonsmoking, nonalcohol drinking (NSND) patients. We performed database searching to identify relevant studies from January 1, 2000 to March 31, 2021. Twenty-six articles from 20 studies were included in this study. We found that these individuals were mostly females in their eighth decade with tumors involving the tongue and gingivobuccal mucosa. This review also observed that these patients were likely diagnosed with early stage tumors with overexpression of programmed death-ligand 1 (PD-L1) and increased intensity of tumor infiltrating lymphocytes. Treatment response and disease-specific prognosis were largely comparable between NSND and smoking/drinking patients

First-Line Atezolizumab Plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis

Background: The IMbrave 150 trial revealed that atezolizumab plus bevacizumab (atezo–bev) improves survival in patients with unresectable hepatocellular carcinoma (HCC) (1 year survival rate: 67.2% vs. 54.6%). We assessed the cost-effectiveness of atezo–bev vs. sorafenib as first-line therapy in patients with unresectable HCC from the US payer perspective. Methods: Using data from the IMbrave 150, we developed a Markov model to compare the lifetime cost and efficacy of atezo–bev as first-line systemic therapy in HCC with those of sorafenib. The main outcomes were life-years, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Results: Atezo–bev demonstrated a gain of 0.44 QALYs, with an additional cost of USD 79,074. The ICER of atezo–bev was USD 179,729 per QALY when compared with sorafenib. The model was most sensitive to the overall survival hazard ratio and body weight. If we assumed that all patients at the end of the IMbrave 150 trial were cured of HCC, atezo–bev was cost-effective (ICER USD 53,854 per QALY). However, if all patients followed the Surveillance, Epidemiology, and End Results data, the ICER of atezo–bev was USD 385,857 per QALY. Reducing the price of atezo–bev by 20% and 29% would satisfy the USD 150,000/QALY and 100,000/QALY willingness-to-pay threshold. Moreover, capping the duration of therapy to ≤12 months or reducing the dosage of bev to ≤10 mg/kg would render atezo–bev cost-effective. Conclusions: The long-term effectiveness of atezo–bev is a critical but uncertain determinant of its cost-effectiveness. Price reduction would favorably influence cost-effectiveness, even if long-term clinical outcomes were modest. Further studies to optimize the duration and dosage of therapy are warranted

Outcomes of nasopharyngeal carcinoma screening for high risk family members in Hong Kong

We undertook a large retrospective study to evaluate the impact of screening family members of NPC patients with Epstein Barr Virus (EBV) serology. 1,199 asymptomatic family members of NPC patients were entered into the annual screening program with EBV serology and nasopharyngoscopy between 1994 and 2005. Eighteen participants of our screening program developed NPC;17 of them were treated in our institute, of whom 16 were detected in screening. The sensitivity and specificity of EBV serology were 83.3 and 87.0%, respectively, and for the program they were 88.9 and 87.0%, respectively. Stage distributions and survival outcomes of the 17 cases were compared with that of 1,185 consecutive symptomatic patients diagnosed in the same period through general referral. It was found that the screening program resulted in early detection of cancer, with 59% presenting at early stage (stage I: 41%, stage II: 18%) compared to 24% (stage I:<1%, stage II: 23%) of symptomatic cancers (P<0.001), and a significant improvement in disease-free survival (P = 0.04). The cancer specific survival and overall survival rate at 5-year are also higher (92 vs. 77% and 92 vs. 70%, respectively), though they fail to reach statistical significance. In conclusion, screening asymptomatic family members of NPC patients annually leads to earlier detection of NPC and clinically valuable survival advantage among these family members. A larger sample size is needed to confirm its full potential in survival benefit. ©Springer Science+Business Media B.V. 2009.Link_to_subscribed_fulltex

Familial nasopharyngeal carcinoma in Hong Kong: Epidemiology and implication in screening

The pathogenetic mechanism of nasopharyngeal carcinoma (NPC) is still unclear. Its familial aggregation, on the other hand, has been well documented by many epidemiological studies. The objective of this study was to evaluate the clinical characteristics of familial NPC in an endemic region. Between March 1994 and November 2005, 1,202 consecutive patients were treated at our institution. Patients were divided into 2 groups according to their family history: group 1 had at least one first-degree relative with NPC at the time of diagnosis, and group 2 did not. There were 125(10.4%) patients in group 1, 66% of them had diseased siblings, 44% had diseased parents and 2% had diseased offspring. The patients in group 1 were on average about 2 years younger than group 2 at diagnosis (47.9 vs. 49.8, P = 0.04). There were also more stage I-II patients in group 1 (37 vs. 23%, P < 0.01). Although the 5 year overall survival was also higher with group 1 (79 vs. 69%, P < 0.01), only age, sex, T classification and N classification were found to be significant independent factors but not family history per se (P = 0.10). Similar findings were observed after excluding screen-detected patients from group 1. The high incidence of familial clustering and improved outcomes from early detection highlight the importance of screening among these high risk family members. © 2008 Springer Science+Business Media B.V.Link_to_subscribed_fulltex

An analysis of the efficacy of serial screening for familial nasopharyngeal carcinoma based on Markov chain models

Treatment of nasopharyngeal carcinoma (NPC) can be improved by early detection of the disease as treatment outcome worsens with disease's progression. This can be achieved with a mass screening program using Epstein Barr virus (EBV) serology and nasopharyngoscopy. The efficacy of any screening strategy should be evaluated before putting it into practice. Such evaluation is ideally performed with simulation as time and cost often preclude the evaluation by randomized trial. This study simulated and compared the outcomes of 4 screening strategies over a period of 12 years: (A) Annual screening, (B) biennial screening, (C) triennial screening, and (D) triennial screening for participants tested EBV negative and annual screening once the participants are tested EBV positive. Progression of the disease was divided into 4 phases and calculated by applying Markov chain model. Parameters of the transition matrix and probabilities were estimated using data from previous screening results of 1,072 family members of NPC patients. The early detection rates with strategies A, B, C and D are 88, 79, 71 and 87% respectively. The 5-year overall survival with screening is 10-12% higher than that without and is the highest with strategies A and D. Strategy D, however, requires only 64% screening tests compared with strategy A and has almost identical resultant disease stage distribution to strategy A. We concluded that strategy D offered the highest efficacy for NPC screening of family members of NPC patients among the four strategies studied. © 2010 Springer Science+Business Media B.V.Link_to_subscribed_fulltex

Clinical outcomes and patterns of failure after intensity-modulated radiotherapy for nasopharyngeal carcinoma

Purpose: To study and report the clinical outcomes and patterns of failure after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). Methods and Materials: The treatment outcomes of NPC patients treated with IMRT at Pamela Youde Nethersole Eastern Hospital between 2005 and 2007 were reviewed. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. Statistical analyses were performed on dose coverage and locoregional failures. Results: A total of 193 NPC patients were analyzed; 93% had Stage III/IV disease. Median follow-up was 30 months. Overall disease failure (at any site) developed in 35 patients. Among these, there were 23 distant metastases, 16 local failures, and 9 regional failures. Four of the locoregional failures were marginal. Dose conformity with IMRT was excellent. Patients with at least 66.5 Gy to their target volumes had significantly less locoregional failure. The 2-year local progression-free, regional progression-free, distant metastasis-free, and overall survival rates were 95%, 96%, 90%, and 92%, respectively. Conclusions: Intensity-modulated radiotherapy provides excellent locoregional control for NPC. Distant metastasis remains the most difficult challenge, and more effective systemic agents should be explored for patients presenting with advanced locoregional diseases. Copyright © 2011 Elsevier Inc.Link_to_subscribed_fulltex