Prevalence of oral human papillomavirus infection among the general adult population in Hong Kong.

A 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.

Changes in the Incidence and Human Papillomavirus-Positive Portion of Oropharyngeal Squamous Cell Carcinoma in Hong Kong.

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.

Effectiveness of mRNA and inactivated COVID-19 vaccines: A test-negative study in an infection-naïve Hong Kong population.

OBJECTIVE: Assess real-world effectiveness of vaccines against COVID-19. METHODS: A test-negative study was conducted in January-May 2022 during an Omicron BA.2 wave in Hong Kong. COVID-19 was identified by RT-PCR. 1-1 case-control matching was based on propensity score with vaccine effectiveness adjusted for confounders. RESULTS: Altogether, 1781 cases and 1737 controls aged 3-105 years were analysed. The mean lag time from the last dose of vaccination to testing for SARS-CoV-2 was 133.9 (SD: 84.4) days. Two doses of either vaccine within 180 days offered a low effectiveness against COVID-19 of all severity combined (VEadj [95% CI] for BNT162b2: 27.0% [4.2-44.5], CoronaVac: 22.9% [1.3-39.7]), and further decreased after 180 days. Two doses of CoronaVac were poorly protective 39.5% [4.9-62.5] against severe diseases for age ≥ 60 years, but the effectiveness increased substantially after the third dose (79.1% [25.7-96.7]). Two doses of BNT162b2 protected age ≥ 60 years against severe diseases (79.3% [47.2, 93.9]); however, the uptake was not high enough to assess three doses. CONCLUSIONS: The current real-world analysis indicates a high vaccine effectiveness of three doses of inactivated virus (CoronaVac) vaccines against Omicron variant, whereas the effectiveness of two doses is suboptimal.

Cross-Clade Memory Immunity in Adults Following SARS-CoV-1 Infection in 2003.

Importance: Knowledge 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. Objectives: To 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 Participants: This 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. Interventions: One 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 Measures: SARS-CoV-2 antibodies were measured prevaccination, 7 days after the first dose, and 14 days after the second dose. Results: Eighteen 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 Relevance: The 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.

Seroprevalence of Unidentified SARS-CoV-2 Infection in Hong Kong During 3 Pandemic Waves.

Importance: Seroprevalence studies inform the extent of infection and assist evaluation of mitigation strategies for the COVID-19 pandemic. Objective: To estimate the prevalence of unidentified SARS-CoV-2 infection in the general population of Hong Kong. Design, Setting, and Participants: A prospective cross-sectional study was conducted in Hong Kong after each major wave of the COVID-19 pandemic (April 21 to July 7, 2020; September 29 to November 23, 2020; and January 15 to April 18, 2021). Adults (age ≥18 years) who had not been diagnosed with COVID-19 were recruited during each period, and their sociodemographic information, symptoms, travel, contact, quarantine, and COVID-19 testing history were collected. Main Outcomes and Measures: The main outcome was prevalence of SARS-CoV-2 infection. SARS-CoV-2 IgG antibodies were detected by an enzyme-linked immunosorbent assay based on spike (S1/S2) protein, followed by confirmation with a commercial electrochemiluminescence immunoassay based on the receptor binding domain of spike protein. Results: The study enrolled 4198 participants (2539 [60%] female; median age, 50 years [IQR, 25 years]), including 903 (22%), 1046 (25%), and 2249 (53%) during April 21 to July 7, 2020; during September 29 to November 23, 2020; and during January 15 to April 18, 2021, respectively. The numbers of participants aged 18 to 39 years, 40 to 59 years, and 60 years or older were 1328 (32%), 1645 (39%), and 1225 (29%), respectively. Among the participants, 2444 (58%) stayed in Hong Kong since November 2019 and 2094 (50%) had negative SARS-CoV-2 RNA test results. Only 170 (4%) reported ever having contact with individuals with confirmed cases, and 5% had been isolated or quarantined. Most (2803 [67%]) did not recall any illnesses, whereas 737 (18%), 212 (5%), and 385 (9%) had experienced respiratory symptoms, gastrointestinal symptoms, or both, respectively, before testing. Six participants were confirmed to be positive for anti-SARS-CoV-2 IgG; the adjusted prevalence of unidentified infection was 0.15% (95% CI, 0.06%-0.32%). Extrapolating these findings to the whole population, there were fewer than 1.9 unidentified infections for every recorded confirmed case. The overall prevalence of SARS-CoV-2 infection in Hong Kong before the roll out of vaccination was less than 0.45%. Conclusions and Relevance: In this cross-sectional study of participants from the general public in Hong Kong, the prevalence of unidentified SARS-CoV-2 infection was low after 3 major waves of the pandemic, suggesting the success of the pandemic mitigation by stringent isolation and quarantine policies even without complete city lockdown. More than 99.5% of the general population of Hong Kong remain naive to SARS-CoV-2, highlighting the urgent need to achieve high vaccine coverage.

A global analysis of replacement of genetic variants of SARS-CoV-2 in association with containment capacity and changes in disease severity.

OBJECTIVES: To examine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant replacement in association with containment capacity and changes in case fatality at country level. METHODS: Altogether, 69 571 full SARS-CoV-2 genomes collected globally within the first 6 months of the pandemic were examined. The correlation between variant replacement and containment capacity was examined by logistic regression models using the WHO International Health Regulation (IHR) score, the Oxford COVID-19 Government Response Tracker (OxCGRT) and the vulnerability index INFORM as proxies, while correlation with changes in monthly crude case fatality ratios was examined by a mixed effect model. RESULTS: At the global level, variant lineage G∗, characterized by the S-D614G mutation, replaced the older lineages L and S in March 2020. European countries-including Finland, France and Italy-were the first to reach a 50% increment of G∗, whereas only Singapore and South Korea had non-G∗ persisting throughout the first 6 months. Countries with higher IHR scores (ß-coefficient -0.001, 95%CI -0.016, -0.001; p 0.034) and higher stringency indexes (OxCGRT) (ß-coefficient -0.011, 95%CI -0.020, -0.001; p 0.035) were associated with lower levels of G∗ replacement, whereas higher vulnerability indexes (INFORM) (ß-coefficient 0.049, 95%CI 0.001, 0.097; p 0.044) were associated with higher replacement levels. Crude case fatality ratio showed a positive correlation with G∗ replacement (ß-coefficient: 0.034, 95%CI 0.011, 0.058; p 0.004), even after adjusting for testing capacity and other country-specific characteristics. CONCLUSIONS: SARS-CoV-2 variant lineage G∗ (S-D614G) replaced older lineages more efficiently in countries with lower containment capacity, and its possible association with increased disease severity deserves further investigation.

Acceptance of the COVID-19 vaccine based on the health belief model: A population-based survey in Hong Kong.

BACKGROUND: Vaccines for COVID-19 are anticipated to be available by 2021. Vaccine uptake rate is a crucial determinant for herd immunity. We examined factors associated with acceptance of vaccine based on (1). constructs of the Health Belief Model (HBM), (2). trust in the healthcare system, new vaccine platforms and manufacturers, and (3). self-reported health outcomes. METHODS: A population-based, random telephone survey was performed during the peak of the third wave of COVID-19 outbreak (27/07/2020 to 27/08/2020) in Hong Kong. All adults aged ≥ 18 years were eligible. The survey included sociodemographic details; self-report health conditions; trust scales; and self-reported health outcomes. Multivariable regression analyses were applied to examine independent associations. The primary outcome is the acceptance of the COVID-19 vaccine. RESULTS: We conducted 1200 successful telephone interviews (response rate 55%). The overall vaccine acceptance rate after adjustment for population distribution was 37.2% (95% C.I. 34.5-39.9%). The projected acceptance rates exhibited a "J-shaped" pattern with age, with higher rates among young adults (18-24 years), then increased linearly with age. Multivariable regression analyses revealed that perceived severity, perceived benefits of the vaccine, cues to action, self-reported health outcomes, and trust in healthcare system or vaccine manufacturers were positive correlates of acceptance; whilst perceived access barriers and harm were negative correlates. Remarkably, perceived susceptibility to infection carried no significant association, whereas recommendation from Government (aOR = 10.2, 95% C.I. 6.54 to 15.9, p < 0.001) was as the strongest driving factor for acceptance. Other key obstacles of acceptance included lack of confidence on newer vaccine platforms (43.4%) and manufacturers without track record (52.2%), which are of particular relevance to the current context. CONCLUSIONS: Governmental recommendation is an important driver, whereas perceived susceptibility is not associated with acceptance of COVID-19 vaccine. These HBM constructs and independent predictors inform evidence-based formulation and implementation of vaccination strategies.

Genomic and evolutionary comparison between SARS-CoV-2 and other human coronaviruses.

Three highly pathogenic human coronaviruses can cause severe acute respiratory syndrome (SARS-CoV, SARS-CoV-2 and MERS-CoV). Although phylogenetic analyses have indicated ancient origin of human coronaviruses from animal relatives, their evolutionary history remains to be established. Using phylogenetics and "high order genomic structures" including trimer spectrums, codon usage and dinucleotide suppression, we observed distinct clustering of all human coronaviruses that formed phylogenetic clades with their closest animal relatives, indicating they have encompassed long evolutionary histories within specific ecological niches before jumping species barrier to infect humans. The close relationships between SARS-CoV and SARS-CoV-2 imply similar evolutionary origin. However, a lower Effective Codon Number (ENC) pattern and CpG dinucleotide suppression in SARS-CoV-2 genomes compared to SARS-CoV and MERS-CoV may imply a better host fitness, and thus their success in sustaining a pandemic. Characterization of coronavirus heterogeneity via complementary approaches enriches our understanding on the evolution and virus-host interaction of these emerging human pathogens while the underlying mechanistic basis in pathogenicity warrants further investigation.

Stringent containment measures without complete city lockdown to achieve low incidence and mortality across two waves of COVID-19 in Hong Kong.

INTRODUCTION: An international city, Hong Kong, in proximity to the first epicentre of COVID- 19, experienced two epidemic waves with different importation pressure. We compared the epidemiological features of patients with COVID-19 in the context of containment policies between the first and second waves. METHODS: We retrieved information on the first 1038 cases detected in Hong Kong (23 January to 25 April 2020) to analyse the epidemiological characteristics including age/gender-specific incidence, clustering, reproduction number (Rt ) and containment delay; in relation to the containment measures implemented. Factors associated with containment delay were evaluated by multiple linear regression analysis with age, gender, epidemic wave and infection source as covariates. A time series of 5-day moving average was plotted to examine the changes across the two epidemic waves. RESULTS: The incidence and mortality (135.5 and 0.5 per 1 000 000 population) was among the lowest in the world. Aggressive escalation of border control correlated with reductions in Rt from 1.35 to 0.57 and 0.92 to 0.18, and aversions of 450 and 1650 local infections during the first and second waves, respectively. Implementing COVID-19 tests for overseas returners correlated with an upsurge of asymptomatic case detection, and shortened containment delay in the second wave. Medium-sized cluster events in the first wave were family gatherings, whereas those in the second wave were leisure activities among youngsters. Containment delay was associated with older age (adjusted OR (AOR)=1.01, 95% CI 1.00 to 1.02, p=0.040), male gender (AOR=1.41, 95% CI 1.02 to 1.96, p=0.039) and local cases (AOR=11.18, 95% CI 7.43 to 16.83, p<0.001), and with significant improvement in the second wave compared with the first wave (average: 6.8 vs 3.7 days). A higher incidence rate was observed for males, raising possibility of gender predilection in susceptibility of developing symptoms. CONCLUSION: Prompt and stringent all-round containment strategies represent successful measures in pandemic control. These findings could inform formulation and implementation of pandemic mitigation strategies.

Serologic Responses in Healthy Adult with SARS-CoV-2 Reinfection, Hong Kong, August 2020.

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.

Prospective Study Comparing Deep Throat Saliva With Other Respiratory Tract Specimens in the Diagnosis of Novel Coronavirus Disease 2019.

BACKGROUND: Self-collected specimens have been advocated to avoid infectious exposure to healthcare workers. Self-induced sputum in those with a productive cough and saliva in those without a productive cough have been proposed, but sensitivity remains uncertain. METHODS: We performed a prospective study in 2 regional hospitals in Hong Kong. RESULTS: We prospectively examined 563 serial samples collected during the virus shedding periods of 50 patients: 150 deep throat saliva (DTS), 309 pooled-nasopharyngeal (NP) and throat swabs, and 104 sputum. Deep throat saliva had the lowest overall reverse-transcriptase polymerase chain reaction (RT-PCR)-positive rate (68.7% vs 89.4% [sputum] and 80.9% [pooled NP and throat swabs]) and the lowest viral ribonucleic acid (RNA) concentration (mean log copy/mL 3.54 vs 5.03 [sputum] and 4.63 [pooled NP and throat swabs]). Analyses with respect to time from symptom onset and severity also revealed similar results. Virus yields of DTS correlated with that of sputum (Pearson correlation index 0.76; 95% confidence interval, 0.62-0.86). We estimated that the overall false-negative rate of DTS could be as high as 31.3% and increased 2.7 times among patients without sputum. CONCLUSIONS: Deep throat saliva produced the lowest viral RNA concentration and RT-PCR-positive rate compared with conventional respiratory specimens in all phases of illness. Self-collected sputum should be the choice for patients with sputum.

SARS-CoV-2 RNA Detection on Disposable Wooden Chopsticks, Hong Kong.

We detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA on disposable wooden chopsticks used by 5 consecutive asymptomatic and postsymptomatic patients admitted for isolation and care at our hospital. Although we did not assess virus viability, our findings may suggest potential for transmission through shared eating utensils.

Persistence and clearance of oral human papillomavirus infections: A prospective population-based cohort study.

OBJECTIVE: This study aimed to evaluate the incidence of and factors associated with persistence and clearance of oral human papillomavirus (HPV) infections. METHOD: A prospective cohort study invited 458 subjects (231 HPV-positive and 227 HPV-negative at baseline) to attend follow-ups at 12 months. Those 231 HPV-positive subjects and 10 new infections were invited to reassessment at 24 months. We used next-gen sequencing for detection and genotyping of HPV. RESULTS: α-HPV infections showed higher persistence rates than ß/γ-HPV (22.7% vs 9.2% at 12 months [P < .05], 10.6% vs 6.8% at 24 months [P = .30]). Clearance rates of α-HPV were lower than ß/γ-HPV at 12 months (31.8% vs 45.1%; P = .05) and higher at 24 months (7.6% vs 4.8%; P = .36). Persistence of ß/γ-HPV was positively associated with males (crude odds ratio [COR] = 3.8, 95% confidence interval [CI] = 1.3-11.2), elderly (51-65 vs 16-50 years; COR = 5.1, 95% CI = 1.2-22.3), and smoking (COR = 4.3, 95% CI = 1.9-9.6). Drinking (COR = 0.5, 95% CI = 0.3-0.9), handwashing less than 90% of times before meals (COR = 0.6, 95% CI = 0.3-0.9), and using public bath more than once per month (COR = 0.5, 95% CI = 0.2-0.9) were risk factors hindering ß/γ-HPV clearance. CONCLUSIONS: This study identified factors associated with persistence and clearance of oral HPV infections among Chinese. Studies on other ethnogeographic groups may further inform prevention strategies of oral HPV infection and immunization programmes.

Prevalence and Epidemiologic Profile of Oral Infection with Alpha, Beta, and Gamma Papillomaviruses in an Asian Chinese Population.

Background: Knowledge of the prevalence of and risk factors for oral human papillomavirus (HPV) infection, especially cutaneous types, is limited. Methods: A population-based study using next-generation sequencing consecutively recruited asymptomatic individuals aged 18-64 years from a proportional sampling of the general population of Hong Kong, according to age groups, gender, and regions of residence. We examined associations of alpha-, beta-, and gamma-HPVs from oral rinse samples with participants' sociodemographics by logistic regression models. Results: The prevalence of oral HPV infection among 1426 ethnic Chinese was 15.5% (95% confidence interval [CI], 13.7%-17.5%), 2.5% (95% CI, 1.8%-3.5%), 11.9% (95% CI, 10.3%-13.6%), and 2.9% (95% CI, 2.1%-3.9%) for any type, alpha-, beta-, and gamma-HPV, respectively. Prevalence of any high-risk HPV was 0.8% (95% CI, 0.4%-1.4%), and that of HPV-16 was 0.4% (95% CI, 0.2%-0.8%). HPV-8 and HPV-98 were the most common beta types detected, while HPV-4 and HPV-SD2R were the most common gamma types. Prevalence of alpha- and beta/gamma-HPV infection showed a similar pattern of increase with age, and was higher in men than women. Smoking, drinking, oral sex, and more sexual partners were associated with alpha-HPV. Teeth brushing before sleep was protective for beta/gamma-HPVs. Discussion: The epidemiologic factors associated with oral infection with alpha-HPVs are different from those of beta/gamma-HPVs, suggesting different modes of acquisition and persistence.

Human papillomaviruses and the specificity of PDZ domain targeting.

The human papillomavirus (HPV) E6 oncoprotein is fundamental to the ability of these viruses to induce human malignancy. A defining characteristic of the HPV E6 oncoproteins found in cancer-causing HPV types is the presence of a PDZ binding motif at their extreme C-terminus. Through this motif, E6 is able to interact with a large number of cellular proteins that contain PDZ domains. Many of these cellular proteins are involved in regulation of processes associated with the control of cell attachment, cell proliferation, cell polarity and cell signaling. How E6 targets multiple proteins containing the same recognition domain is still an open question. In this review, we highlight aspects of E6 function and biology that help to answer this question, and thereby provide insight into the role of these substrates during development of HPV-induced malignancy.