Boon Siaw Shi
@cuhk.edu.hk
Department of Microbiology, Faculty of Medicine
The Chinese University of Hong Kong
RESEARCH INTERESTS
1. Viral pathogenesis
2. Cancer biology
3. Cell signalling pathways
4. Anti-viral compounds
Scopus Publications
Scopus Publications
Wendy C. S. Ho, Siaw S. Boon, Ka Chun Chong, Christopher K. C. Lai, Ryan K. H. Sze, Aaron T. K. Khan, Rachel L. Xing, Isaya Sukarom, Ying‐Hui Wu, Rene W. Y. Chau,et al.
Wiley
AbstractA cross‐sectional study in 2021−23 collected oral rinse gargle samples from an human papillomaviruses (HPV) vaccine‐naïve general adult population in Hong Kong. HPV was detected by a PCR using SPF10 primers, and genotyped by a linear array covering 25 genotypes. Epidemiologic information including sociodemographics, medical history, oral health, and sexual behavior were collected by a self‐administered questionnaire. Altogether, 2323 subjects aged 18−75 (median 47) years with 50.1% male were recruited. The prevalence for oral HPV infection with all genotypes combined, high‐risk, and low‐risk genotypes was 1.5%, 0.7%, and 0.7%, respectively; and with no statistically significant difference between participant gender. The prevalence increased with age and was highest in women at 45−54 years (2.7% for all genotypes combined), and highest in men aged >64 years (4.1% for all genotypes combined). HPV52 was the most common genotype among all participants. Univariate analysis suggested more lifetime sexual or oral sexual partners as risk factors, but they did not reach statistical significance upon multivariate analysis; whereas higher educational level had an independent protective effect. To conclude, oral HPV prevalence increased with age in Hong Kong. Strategies to prevent oral HPV infection and the associated cancers are urgently needed.
Zigui Chen, Rita Way Yin Ng, Grace Lui, Lowell Ling, Agnes S.Y. Leung, Chit Chow, Siaw Shi Boon, Wendy C.S. Ho, Maggie Haitian Wang, Renee Wan Yi Chan,et al.
Elsevier BV
Zigui Chen, Amy B. W. Chan, Lok-Sang Kam, Man-Hin Chan, Jason Y. K. Chan, Wai-Tung Lee, Chit Chow, Siaw S. Boon, Chichao Xia, Brian Lam,et al.
MDPI AG
The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in association with other head and neck cancers. Archived tumor tissues were tested for HPV. From 1986 to 2020, there was a marked decrease in the incidence of nasopharyngeal and laryngeal cancers, but a persistent increase in OPSCC from 36 cases in 1986 to 116 cases in 2020. The average positive rate for high-risk HPV was 36.1% (112/310) among OPSCC diagnosed in 2010–2020. The HPV-positive rate in recent years was significantly higher than earlier cases (tonsil SCC: 64.7% (55/85) in 2016–2020 vs. 40.4% (19/47) in 2010–2015, p = 0.007). Patients with HPV-positive tonsil cancers were significantly younger than those negative (mean [SD]: 58.9 [9.9] vs. 64.3 [13.3] years, p = 0.006), but no significant difference was observed between genders. A persistent increase in the incidence of oropharyngeal cancer over the last few decades was observed in Hong Kong, which can be explained by the remarkable increase in HPV-positive tonsil cancers.
Josipa Skelin, Ho Yin Luk, Dražan Butorac, Siaw Shi Boon, and Vjekoslav Tomaić
Wiley
AbstractHuman papillomavirus (HPV) infections are a leading cause of viral‐induced malignancies worldwide, with a prominent association with cervical and head and neck cancers. The pivotal role of HPV oncoproteins, E5, E6, and E7, in manipulating cellular events, which contribute to viral pathogenesis in various ways, has been extensively documented. This article reviews the influence of HPV oncoproteins on cellular signaling pathways within the host cell, shedding light on the underlying molecular mechanisms. A comprehensive understanding of these molecular alterations is essential for the development of targeted therapies and strategies to combat HPV‐induced premalignancies and prevent their progress to cancer. Furthermore, this review underscores the intricate interplay between HPV oncoproteins and some of the most important cellular signaling pathways: Notch, Wnt/β‐catenin, MAPK, JAK/STAT, and PI3K AKT/mTOR. The treatment efficacies of the currently available inhibitors on these pathways in an HPV‐positive context are also discussed. This review also highlights the importance of continued research to advance our knowledge and enhance therapeutic interventions for HPV‐associated diseases.
Chichao Xia, Chuanyun Xiao, Ho Yin Luk, Paul K. S. Chan, and Siaw Shi Boon
Springer Science and Business Media LLC
Rita W.Y. Ng, Ryan K.H. Sze, Ka Chun Chong, Shi Zhao, Lowell Ling, Grace Lui, Agnes S.Y. Leung, Apple C.M. Yeung, Wendy C.S. Ho, Martin C.S. Wong,et al.
Elsevier BV
Siaw Shi Boon, Yin Ching Lee, Ka Lai Yip, Ho Yin Luk, Chuanyun Xiao, Man Kin Yim, Zigui Chen, and Paul Kay Sheung Chan
MDPI AG
The human papillomavirus E6 and E7 oncoproteins interact with a different subset of host proteins, leading to dysregulation of the apoptotic, cell cycle, and signaling pathways. In this study, we identified, for the first time, that Aurora kinase B (AurB) is a bona fide interacting partner of E6. We systematically characterized the AurB-E6 complex formation and its consequences in carcinogenesis using a series of in vitro and cell-based assays. We also assessed the efficacy of Aurora kinase inhibitors in halting HPV-mediated carcinogenesis using in vitro and in vivo models. We showed that AurB activity was elevated in HPV-positive cells, and this correlated positively with the E6 protein level. E6 interacted directly with AurB in the nucleus or mitotic cells. A previously unidentified region of E6, located upstream of C-terminal E6-PBM, was important for AurB-E6 complex formation. AurB-E6 complex led to reduced AurB kinase activity. However, the AurB-E6 complex increased the hTERT protein level and its telomerase activity. On the other hand, AurB inhibition led to the inhibition of telomerase activity, cell proliferation, and tumor formation, even though this may occur in an HPV-independent manner. In summary, this study dissected the molecular mechanism of how E6 recruits AurB to induce cell immortalization and proliferation, leading to the eventual cancer development. Our findings revealed that the treatment of AZD1152 exerted a non-specific anti-tumor effect. Hence, a continuous effort to seek a specific and selective inhibitor that can halt HPV-mediated carcinogenesis should be warranted.
Sile Li, Man Kin Yim, Ka Lai Yip, Chuanyun Xiao, Ho Yin Luk, Sijia Xiao, Zigui Chen, Paul K. S. Chan, and Siaw Shi Boon
American Society for Microbiology
We unveiled the mechanism of how HPV employs Aurora kinase A (AurA) of host cells to exert its oncogenic capability synergistically. We systematically characterized the mode of interaction between E6-encoded by cancer-causing HPV and AurA.
Rita W. Y. Ng, Siaw S. Boon, Zigui Chen, Wendy C. S. Ho, Kitty S. C. Fung, Barry K. C. Wong, Apple C. M. Yeung, Martin C. S. Wong, and Paul K. S. Chan
American Medical Association (AMA)
ImportanceKnowledge of the longevity and breath of immune response to coronavirus infection is crucial for the development of next-generation vaccines to control the COVID-19 pandemic.ObjectivesTo determine the profile of SARS-CoV-2 antibodies among persons infected with the closely related virus, SARS-CoV-1, in 2003 (SARS03 survivors) and to characterize their antibody response soon after the first and second doses of COVID-19 vaccines.Design, Setting, and ParticipantsThis prospective cohort study examined SARS-CoV-2 antibodies among SARS03 survivors compared with sex- and age-matched infection-naive controls. Participants received the COVID-19 vaccines between March 1 and September 30, 2021.InterventionsOne of the 2 COVID-19 vaccines (inactivated [CoronaVac] or messenger RNA [BNT162b2]) available in Hong Kong. Two doses were given according to the recommended schedule. The vaccine type administered was known to both participants and observers.Main Outcomes and MeasuresSARS-CoV-2 antibodies were measured prevaccination, 7 days after the first dose, and 14 days after the second dose.ResultsEighteen SARS03 adult survivors (15 women and 3 men; median age, 46.5 [IQR, 40.0-54.3] years) underwent prevaccination serologic examination. The vast majority retained a detectable level of antibodies that cross-reacted with SARS-CoV-2 (16 of 18 [88.9%] with nucleocapsid protein antibodies and 17 of 18 [94.4%] with receptor-binding domain of spike protein antibodies); a substantial proportion (11 of 18 [61.1%]) had detectable cross-neutralizing antibodies. Twelve SARS03 adult survivors (10 women and 2 men) underwent postvaccination serologic examination. At 7 days after the first dose of vaccine, SARS03 survivors mounted significantly higher levels of neutralizing antibodies compared with controls (median inhibition: 89.5% [IQR, 77.1%-93.7%] vs 13.9% [IQR, 11.8%-16.1%] for BNT162b2; 64.9% [IQR, 60.8%-69.5%] vs 13.4% [IQR, 9.5%-16.8%] for CoronaVac; P < .001 for both). At 14 days after the second dose, SARS03 survivors generated a broader antibody response with significantly higher levels of neutralizing antibodies against variants of concern compared with controls (eg, median inhibition against Omicron variant, 52.1% [IQR, 35.8%-66.0%] vs 14.7% [IQR, 2.5%-20.7%]; P < .001).Conclusions and RelevanceThe findings of this prospective cohort study suggest that infection with SARS-CoV-1 was associated with detectable levels of antibodies that cross-react and cross-neutralize SARS-CoV-2, which belongs to a distinct clade under the same subgenus Sarbecovirus. These findings support the development of broadly protective vaccines to cover sarbecoviruses that caused 2 devastating zoonotic outbreaks in humans over the last 2 decades.
Christopher KC Lai, Grace CY Lui, Yuchen Wei, Ka Chun Chong, Zigui Chen, Lowell Ling, Rita WY Ng, Siaw SS Boon, Wendy CS Ho, Apple CM Yeung,et al.
Elsevier BV
Jason Y.K. Chan, Man Kit Cheung, Linlin Lan, Cherrie Ng, Eric H.L. Lau, Zenon W.C. Yeung, Eddy W.Y. Wong, Leanne Leung, Xinyu Qu, Liuyang Cai,et al.
Elsevier BV
Christopher K. C. Lai, Man Kit Cheung, Grace C. Y. Lui, Lowell Ling, Jason Y. K. Chan, Rita W. Y. Ng, Hiu Ching Chan, Apple C. M. Yeung, Wendy C. S. Ho, Siaw Shi Boon,et al.
American Society for Microbiology
Our results showed that while both COVID-19 and non-COVID-19 hospitalized patients differed in the composition, alpha and beta diversity, and metabolic potential of the naso-oropharyngeal microbiota compared with local controls, the microbial communities in the two hospitalized patient groups did not differ significantly from each other, indicating a limited impact of SARS-CoV-2 on the naso-oropharyngeal microbiota in hospitalized patients. Besides, we identified Alloprevotella and Solobacterium as bacterial genera uniquely enriched in COVID-19 patients, which may serve as more specific biomarkers for COVID-19 detection.
Siaw Shi Boon, Ho Yin Luk, Chuanyun Xiao, Zigui Chen, and Paul Kay Sheung Chan
MDPI AG
Cancer arising from the uterine cervix is the fourth most common cause of cancer death among women worldwide. Almost 90% of cervical cancer mortality has occurred in low- and middle-income countries. One of the major aetiologies contributing to cervical cancer is the persistent infection by the cancer-causing types of the human papillomavirus. The disease is preventable if the premalignant lesion is detected early and managed effectively. In this review, we outlined the standard guidelines that have been introduced and implemented worldwide for decades, including the cytology, the HPV detection and genotyping, and the immunostaining of surrogate markers. In addition, the staging system used to classify the premalignancy and malignancy of the uterine cervix, as well as the safety and efficacy of the various treatment modalities in clinical trials for cervical cancers, are also discussed. In this millennial world, the advancements in computer-aided technology, including robotic modules and artificial intelligence (AI), are also incorporated into the screening, diagnostic, and treatment platforms. These innovations reduce the dependence on specialists and technologists, as well as the work burden and time incurred for sample processing. However, concerns over the practicality of these advancements remain, due to the high cost, lack of flexibility, and the judgment of a trained professional that is currently not replaceable by a machine.
Sile Li, Ho Yin Luk, Chichao Xia, Zigui Chen, Paul Kay Sheung Chan, and Siaw Shi Boon
Elsevier BV
Zigui Chen, Rita Way Yin Ng, Grace Lui, Lowell Ling, Chit Chow, Apple Chung Man Yeung, Siaw Shi Boon, Maggie Haitian Wang, Kate Ching Ching Chan, Renee Wan Yi Chan,et al.
American Society for Microbiology
Attempts to use subgenomic RNAs (sgRNAs) of SARS-CoV-2 to identify active infection of COVID-19 have produced diverse results. In this work, we applied next-generation sequencing and RT-PCR to profile the full spectrum of SARS-CoV-2 sgRNAs in a large cohort of respiratory and stool samples collected throughout infection.
Rita Wai-Yin Ng, Chun-Kwok Wong, Grace Chung-Yan Lui, Eugene Yuk-Keung Tso, Zigui Chen, Owen Tak-Yin Tsang, Siaw Shi Boon, Christopher Koon-Chi Lai, Kitty Sau-Chun Fung, Apple Chung-Man Yeung,et al.
Elsevier BV
Siaw S. Boon, Martin C. S. Wong, Rita W. Y. Ng, Danny T. M. Leung, Zigui Chen, Christopher K. C. Lai, Wendy C. S. Ho, Junjie Huang, Barry K. C. Wong, Kitty S. C. Fung,et al.
American Medical Association (AMA)
This cross-sectional study estimates the prevalence of unidentified SARS-CoV-2 infection in the general population of Hong Kong after 3 major pandemic waves.
Siaw Shi Boon, Chichao Xia, Maggie Haitian Wang, Ka Lai Yip, Ho Yin Luk, Sile Li, Rita W. Y. Ng, Christopher K. C. Lai, Paul Kay Sheung Chan, and Zigui Chen
American Society for Microbiology
Our study showed the global distribution of SARS-CoV-2 S protein variants from January 2020 to the end of April 2021. We highlighted the key amino acids of S protein subjected to positive selection.
Chichao Xia, Sile Li, Teng Long, Zigui Chen, Paul K. S. Chan, and Siaw Shi Boon
MDPI AG
Human papillomavirus (HPV) infection remains one of the most prominent cancer-causing DNA viruses, contributing to approximately 5% of human cancers. While association between HPV and cervical cancers has been well-established, evidence on the attribution of head and neck cancers (HNC) to HPV have been increasing in recent years. Among the cancer-causing HPV genotypes, HPV16 and 18 remain the major contributors to cancers across the globe. Nonetheless, the distribution of HPV genotypes in ethnically, geographically, and socio-economically diverse East, Southeast, and South Asia may differ from other parts of the world. In this review, we garner and provide updated insight into various aspects of HPV reported in recent years (2015–2021) in these regions. We included: (i) the HPV genotypes detected in normal cancers of the uterine cervix and head and neck, as well as the distribution of the HPV genotypes by geography and age groups; (ii) the laboratory diagnostic methods and treatment regimens used within these regions; and (iii) the oncogenic properties of HPV prototypes and their variants contributing to carcinogenesis. More importantly, we also unveil the similarities and discrepancies between these aspects, the areas lacking study, and the challenges faced in HPV studies.
Zigui Chen, Ka Chun Chong, Martin C.S. Wong, Siaw S. Boon, Junjie Huang, Maggie H. Wang, Rita W.Y. Ng, Christopher K.C. Lai, and Paul K.S. Chan
Elsevier BV
Zigui Chen, Siaw S. Boon, Maggie H. Wang, Renee W.Y. Chan, and Paul K.S. Chan
Elsevier BV
Martin C.S. Wong, Eliza L.Y. Wong, Junjie Huang, Annie W.L. Cheung, Kevin Law, Marc K.C. Chong, Rita W.Y. Ng, Christopher K.C. Lai, Siaw S. Boon, Joseph T.F. Lau,et al.
Elsevier BV
Tao Zuo, Qin Liu, Fen Zhang, Grace Chung-Yan Lui, Eugene YK Tso, Yun Kit Yeoh, Zigui Chen, Siaw Shi Boon, Francis KL Chan, Paul KS Chan,et al.
BMJ
ObjectiveAlthough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in faeces of patients with COVID-19, the activity and infectivity of the virus in the GI tract during disease course is largely unknown. We investigated temporal transcriptional activity of SARS-CoV-2 and its association with longitudinal faecal microbiome alterations in patients with COVID-19.DesignWe performed RNA shotgun metagenomics sequencing on serial faecal viral extractions from 15 hospitalised patients with COVID-19. Sequencing coverage of the SARS-CoV-2 genome was quantified. We assessed faecal microbiome composition and microbiome functionality in association with signatures of faecal SARS-CoV-2 infectivity.ResultsSeven (46.7%) of 15 patients with COVID-19 had stool positivity for SARS-CoV-2 by viral RNA metagenomic sequencing. Even in the absence of GI manifestations, all seven patients showed strikingly higher coverage (p=0.0261) and density (p=0.0094) of the 3’ vs 5’ end of SARS-CoV-2 genome in their faecal viral metagenome profile. Faecal viral metagenome of three patients continued to display active viral infection signature (higher 3’ vs 5’ end coverage) up to 6 days after clearance of SARS-CoV-2 from respiratory samples. Faecal samples with signature of high SARS-CoV-2 infectivity had higher abundances of bacterial species Collinsella aerofaciens, Collinsella tanakaei, Streptococcus infantis, Morganella morganii, and higher functional capacity for nucleotide de novo biosynthesis, amino acid biosynthesis and glycolysis, whereas faecal samples with signature of low-to-none SARS-CoV-2 infectivity had higher abundances of short-chain fatty acid producing bacteria, Parabacteroides merdae, Bacteroides stercoris, Alistipes onderdonkii and Lachnospiraceae bacterium 1_1_57FAA.ConclusionThis pilot study provides evidence for active and prolonged ‘quiescent’ GI infection even in the absence of GI manifestations and after recovery from respiratory infection of SARS-CoV-2. Gut microbiota of patients with active SARS-CoV-2 GI infection was characterised by enrichment of opportunistic pathogens, loss of salutary bacteria and increased functional capacity for nucleotide and amino acid biosynthesis and carbohydrate metabolism.
Paul K.S. Chan, Grace Lui, Asmaa Hachim, Ronald L.W. Ko, Siaw S. Boon, Timothy Li, Niloufar Kavian, Fion Luk, Zigui Chen, Emily M. Yau,et al.
Centers for Disease Control and Prevention (CDC)
In March 2020, mild signs and symptoms of coronavirus disease developed in a healthy 33-year-old man in Hong Kong. His first infection did not produce virus neutralizing antibodies. In August, he had asymptomatic reinfection, suggesting that persons without a robust neutralizing antibody response might be at risk for reinfection.
Martin C. S. Wong, Alexander C. Vlantis, Miaoyin Liang, Po Yee Wong, Wendy C. S. Ho, Siaw S. Boon, Colette Leung, Paul K. S. Chan, and Zigui Chen
Wiley
This study aimed to evaluate the incidence of and factors associated with persistence and clearance of oral human papillomavirus (HPV) infections.