published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Background: Human papillomavirus (HPV) DNA test is more sensitive and can detect more high-grade cervical intraepithelial lesions than cytology test in cervical cancer screening. There are studies confirming HPV test being more effective in cervical cancer screening by detecting the persistence of HPV infection that could lead to cancer. However, the costs associated with a HPV test is higher than a cytology test. Moreover, HPV test is less specific which could subject more women to further triage tests or unnecessary invasive diagnostic procedures. Therefore healthcare costs could possibly increase if primary HPV screening is to be adopted. Study objective: The aim of the study is to systematically review the cost-effectiveness of primary HPV testing in cervical cancer screening Method: Electronic search was performed in three biomedical databases (PubMed, Medline, Cochrane Library) and one economic evaluation database to identify relevant studies. Studies were selected according to the explicit inclusion and exclusion criteria defined. Only those studies carried out in high-income countries were included so that result could be better applied to Hong Kong. Results: A total of 19 studies were included in this systematic review. Cytology-only method is generally not cost-effective. To be cost-effective, it has to be performed in a longer screening interval which would reduce not only the screening costs but also a reduction in the health outcomes. Among the different options in HPV-based primary screening, HPV testing with cytology triage is the most cost-effective strategy in many of the studies. Combined HPV/cytology co-screening could achieve the biggest health benefit but is also most costly. HPV-based screening is more cost-effective for those >30 years of age and is usually less cost-effective if applied to young women. From the result in sensitivity analysis, HPV-based screening is sensitive to an increase in the costs of the HPV test, a low HPV test sensitivity and a low screening compliance rate. Conclusion: Primary HPV screening is cost-effective and generally performs better than cytology screening. The result of this systematic review guides the future direction of developing an optimal cervical screening strategy in Hong Kong. Local context has to be considered when examining the cost-effectiveness of primary HPV testing for cervical screening. Good quality local epidemiological data on HPV infection and cervical cancer and screening would be required to aid future research on the application of HPV test for cervical cancer screening in Hong Kong. / published_or_final_version / Public Health / Master / Master of Public Health

Cervical cancer is one of the common cancers among women and poses a great burden to the public health. Currently there are two human papillomavirus vaccines, CervarixTM and Gardasil®, against HPV type 16/18 and type 6/11/16/18 cervical cancer available in the market. Most clinical trials about immunogenicity and safety of the two vaccines were conducted among Caucasian females, rather than on Asian female populations. This systematic review aims to summarize and evaluate immunogenicity and safety of the two vaccines conducted mainly at the setting of randomized control trials on Asian female populations. This investigation would enhance understanding about whether ethnic difference impacts antibody responses, what were the severe adverse events in Asian populations, and whether the vaccines demonstrate satisfactory immunogenicity. Eleven relevant studies were identified from Pubmed and Medline with totally 4026 subjects involved. The quality and validity of these studies was critically appraised in terms of randomization, allocation ratio, blinding, analytical methods and other potential limitations. The two vaccines demonstrated high geometric mean antibody titer levels among Asian females. Injection-site pain was the mostly complained solicited local symptom, followed by redness and swelling. Few severe solicited local symptoms were reported. The unsolicited symptoms were not as common as solicited symptoms and quite a few of them were not related to the vaccination. One severe adverse event was confirmed in Japan’s study – a spontaneous abortion had taken place 15 days after vaccination. China lacks of systematic cancer registries, therefore it is difficult to estimate the disease burden. China’s Gross Domestic Product only reached $5445 per capita in 2011. HPV vaccination would not be cost-effective in the countries which had Gross Domestic Product lower than $8505 per capita, therefore piloting the HPV vaccination in major economic powerhouses like Shanghai and Beijing would be more realistic. To sum up, this systematic review demonstrated satisfactory immunogenicity on Asian females. The safety data were acceptable to some extent except one spontaneous abortion occurred in Japan’s study. / published_or_final_version / Public Health / Master / Master of Public Health

In cervical screening programmes, Papanicolaou test (Pap test) is the key screening tool. However Pap test is difficult to implement in low-resource region. Introduction of an economic, cost-effective and less skill demanding equipment is hence a potential direction of advance in cervical screening methodology. 　　Cervical carcinogenesis involves genetic instability which leads to chromosomal aneuploidy. Evaluation of aneuploidy may hence provide information for identifying cancer and precursor cells. An automated DNA-image-cytometry system (DNA-imager) capable of quantitating the DNA content of cells has recently been developed. 　　To evaluate the efficacy of DNA-imager in cervical cancer screening, a total of 483 residual ThinPrep liquid-based cytology (LBC) samples after diagnosis were retrieved and evaluated by the DNA-imager. The high risk human papillomavirus (HPV) status of the atypical squamous cells of undetermined significance (ASC-US) samples has been tested as a parallel study. According to established criteria, 423 out of the 483 samples were satisfactory for downstream analysis. The samples were designated “Normal”, “Suspicious” or “Abnormal” according to their DNA aneuploidy and proliferation activity. 　　Significantly more high grade lesion samples (HSIL and SCC) were designated as “Abnormal” by DNA-imager than were lower grade lesion samples (Negative, ASC-US, AGC, ASC-H, and LSIL) (94.19% vs 51.04%, p<0.0001). For detecting ≥HSIL, DNA-imager achieved high sensitivity and specificity (94.19% and 48.96%) using “Abnormal” as cut off. Adopting a more stringent definition of “Suspicious” or “Abnormal” would increase the sensitivity to 100% but decreased the specificity to 24.33%. 　　 　　Regarding ASC-US triage, DNA-imager achieved a sensitivity and specificity of 80.00% and 71.29% respectively when “Abnormal” was used as test positive to predict cases with ≥HSIL follow-up in the next two year. The sensitivity increased but the specificity decreased to 90.00% and 34.65% respectively if “Suspicious or above” was used as indicator of undesirable follow-up. HR-HPV test, on the other hand, was able to identify all cases with ≥HSIL upon follow-up (sensitivity = 100%) but the specificity was only 15.84%. Among these ASC-US sample, test positivity of the two tests showed poor concordance with each other (Cohen’s κ = 0.062 and 0.074 respectively for “Suspicious or above” or “Abnormal”, respectively). 　　Our findings suggested that DNA-imager may be a useful tool for automated primary screening of cervical cancer 3 / published_or_final_version / Pathology / Master / Master of Medical Sciences

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_version / Public Health / Doctoral / Doctor of Philosophy

published_or_final_version / Surgery / Master / Master of Surgery

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

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