Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G.

The SARS-CoV-2 Omicron variants are notorious for their transmissibility, but little is known about their subgenomic RNA (sgRNA) expression. This study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern (non-VOC)-D614G. A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOC-D614G regardless of host gender, age and presence of pneumonia. Remarkably, such profile was lost in samples with low viral load, suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point. A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and non-VOC-D614G. The presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load (AUC â€‹= â€‹0.91, 95% CI 0.88-0.94), and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual patient. Further potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

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.

Development of the early-life gut microbiome and associations with eczema in a prospective Chinese cohort.

IMPORTANCE: Eczema is a major allergic disease in children, which is particularly prevalent in Chinese children during their first year of life. In this study, we showed that alterations in the infant gut microbiota precede the development of eczema in a prospective Chinese cohort. In particular, we discovered enrichments of the genera Clostridium sensu stricto 1 and Finegoldia in the cases at 3 and 1 month of age, respectively, which may represent potential targets for intervention to prevent eczema. Besides, we identified a depletion of Bacteroides from 1 to 6 months of age and an enrichment of Clostridium sensu stricto 1 at 3 months in the eczema cases, patterns also observed in C-section-born infants within the same time frames, providing first evidence to support a role of the gut microbiota in previously reported associations between C-section and increased risk of eczema in infancy.

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.

Extent of Oral-Gut Transmission of Bacterial and Fungal Microbiota in Healthy Chinese Adults.

Recent studies have provided evidence on the presence of an oral-gut microbiota axis in gastrointestinal diseases; however, whether a similar axis exists in healthy individuals is still in debate. Here, we characterized the bacterial and fungal microbiomes in paired oral rinse and stool samples collected from 470 healthy Chinese adults by sequencing the 16S rRNA V3-V4 and ITS1 regions, respectively. We hypothesized that there is limited oral-gut transmission of both the bacterial and fungal microbiota in healthy Chinese adults. Our results showed that the oral and gut microbiota in healthy individuals differed in taxonomic composition, alpha and beta diversity, metabolic potential, and network properties. Bayesian analysis showed that the vast majority of subjects had negligible or low bacterial and fungal oral-to-stool contribution. Detailed examination of the prevalent amplicon sequence variants (ASVs) also revealed limited cases of sharing between the oral and stool samples within the same individuals, except a few bacterial and fungal ASVs. Association analysis showed that sharing of the potentially transmissible fungal ASVs was associated with host factors, including an older age and a higher body mass index. Our findings indicate that oral-gut transmission of both bacterial and fungal microbiota in healthy adults is limited. Detection of a large amount of shared bacterial or fungal members between the oral and gut microbiome of an individual may indicate medical conditions that warrant detailed checkup. IMPORTANCE The oral-gut microbiota axis in health is a fundamentally important and clinically relevant topic; however, our current understanding of it remains biased and incomplete. By characterizing the bacterial and fungal microbiomes in paired oral rinse and stool samples from a large cohort of healthy Chinese adults, here we provided new evidence that oral-gut microbiota transmission is limited in non-Western population and across biological domains. Our study has established an important baseline of a healthy oral-gut microbiota axis, with which other disease conditions can be compared. Besides, our findings have practical implications that detection of a large amount of shared bacterial or fungal members between the oral cavity and gut within the same individual as an indicator of potential medical conditions.

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.

Limited Impact of SARS-CoV-2 on the Human Naso-Oropharyngeal Microbiota in Hospitalized Patients.

Numerous studies have reported dysbiosis in the naso- and/or oro-pharyngeal microbiota of COVID-19 patients compared with healthy individuals; however, only a few small-scale studies have also included a disease control group. In this study, we characterized and compared the bacterial communities of pooled nasopharyngeal and throat swabs from hospitalized COVID-19 patients (n = 76), hospitalized non-COVID-19 patients with respiratory symptoms or related illnesses (n = 69), and local community controls (n = 76) using 16S rRNA gene V3-V4 amplicon sequencing. None of the subjects received antimicrobial therapy within 2 weeks prior to sample collection. 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. However, the microbial communities in the two hospitalized patient groups did not differ significantly from each other. Differential abundance analysis revealed the enrichment of nine bacterial genera in the COVID-19 patients compared with local controls; however, six of them were also enriched in the non-COVID-19 patients. Bacterial genera uniquely enriched in the COVID-19 patients included Alloprevotella and Solobacterium. In contrast, Mogibacterium and Lactococcus were dramatically decreased in COVID-19 patients only. Association analysis revealed that Alloprevotella in COVID-19 patients was positively correlated with the level of the inflammation biomarker C-reactive protein. Our findings reveal a limited impact of SARS-CoV-2 on the naso-oropharyngeal microbiota in hospitalized patients and suggest that Alloprevotella and Solobacterium are more specific biomarkers for COVID-19 detection. IMPORTANCE 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.

Determinants and Interactions of Oral Bacterial and Fungal Microbiota in Healthy Chinese Adults.

Numerous studies have examined the composition of and factors shaping the oral bacterial microbiota in healthy adults; however, similar studies on the less dominant yet ecologically and clinically important fungal microbiota are scarce. In this study, we characterized simultaneously the oral bacterial and fungal microbiomes in a large cohort of systemically healthy Chinese adults by sequencing the bacterial 16S rRNA gene and fungal internal transcribed spacer. We showed that different factors shaped the oral bacterial and fungal microbiomes in healthy adults. Sex and age were associated with the alpha diversity of the healthy oral bacterial microbiome but not that of the fungal microbiome. Age was also a major factor affecting the beta diversity of the oral bacterial microbiome; however, it only exerted a small effect on the oral fungal microbiome when compared with other variables. After controlling for age and sex, the bacterial microbiota structure was most affected by marital status, recent oral conditions and oral hygiene-related factors, whereas the fungal microbiota structure was most affected by education level, fruits and vegetables, and bleeding gums. Bacterial-fungal interactions were limited in the healthy oral microbiota, with the strongest association existing between Pseudomonas sp. and Rhodotorula dairenensis. Several bacterial amplicon sequence variants (ASVs) belonging to Veillonella atypica and the genera Leptotrichia, Streptococcus and Prevotella_7 and fungal ASVs belonging to Candida albicans and the genus Blumeria were revealed as putative pivotal members of the healthy oral microbiota. Overall, our study has facilitated understanding of the determining factors and cross-kingdom interactions of the healthy human oral microbiome. IMPORTANCE Numerous studies have examined the bacterial community residing in our oral cavity; however, information on the less dominant yet ecologically and clinically important fungal members is limited. In this study, we characterized simultaneously the oral bacterial and fungal microbial communities in a large cohort of healthy Chinese adults, examined their associations with an array of host factors, and explored potential interactions between the two microbial groups. We showed that different factors shape the diversity and structure of the oral bacterial and fungal microbial communities in healthy adults, with, for instance, sex and age only associated with the diversity of the bacterial community but not that of the fungal community. Besides, we found that bacterial-fungal interactions are limited in the healthy oral cavity. Overall, our study has facilitated understanding of the determining factors and bacterial-fungal interactions of the healthy human oral microbial community.

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.

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.

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.

Non-human Primate Papillomaviruses Share Similar Evolutionary Histories and Niche Adaptation as the Human Counterparts.

Given high genetic diversity of papillomaviruses (PV) and complex scenario of virus-host interaction, the genetic basis underlying the mechanisms of HPV carcinogenicity is not well understood. In an effort to evaluate the origin and evolution of PV pathogenicity, we collected paired oral, perianal, and genital swabs from a wild macaque population. Of the 117 surveyed macaques, 88 (75.2%) were positive for PV DNA in one or more sites, mostly common from genital swabs, followed by oral and perianal sites. All putative macaque PV types phylogenetically clustered into the genera Alpha-, Beta-, and Gammapapillomavirus, with a strong phylogeny-tropism association as observed in HPVs. Using a Bayesian Markov Chain Monte Carlo framework, we demonstrated ancient intra-host divergence of primate PVs in which multiple ancestors had split and adapted to specific host ecosystems at least 41 million years ago, prior to the speciation events of primate host species. Following subsequent divergence and niche adaptation, distinct but phylogenetically related PV types were transmitted to similar host ecosystems by closely related host animals when host speciation occurred, which may explain in part the origin of carcinogenicity of HPV type 16 (HPV16) and Macaca fascicularis PV type 3 (MfPV3) that evolved from a most recent common ancestor containing the determinants for cervicovaginal colonization and cervical cancer. The findings identifying evolutionary and biological relatedness between human and non-human primate PVs lay a genetic foundation for research on parasite-host interactions and carcinogenic outcomes, which will prove useful in further study of viral pathogenesis and host specificity. STUDY IMPORTANCE: To better understand the origin and evolution of PV carcinogenicity associated with cervical cancer, we applied a combination of phylogenetic and bioinformatic analyses to investigate the genetic diversity of macaque papillomaviruses, and estimate divergence times of human and non-human primate PVs. The majority of both human and non-human primate PVs cluster into α-, ß-, and γ-PVs, sharing similar evolutionary histories and biological properties to each other. The strong phylogeny-tropism association of primate PVs indicates an important role of niche adaptation and virus-host codivergence shaping the diversity of viral genomics, host specificity, immune exposure, and pathogenic property. Understanding the evolution of the family Papilloamviridae in general and the primate papillomaviruses in specific in relevant to virus-host interactions should provide important implications for viral pathogenesis and disease prevention.

Impact of inter- and intra-individual variation, sample storage and sampling fraction on human stool microbial community profiles.

Stools are commonly used as proxies for studying human gut microbial communities as sample collection is straightforward, cheap and non-invasive. In large-scale human population surveys, however, sample integrity becomes an issue as it is not logistically feasible for researchers to personally collect stools from every participant. Instead, participants are usually given guidelines on sample packaging and storage, and asked to deliver their stools to a centralised facility. Here, we tested a number of delivery conditions (temperature, duration and addition of preservative medium) and assessed their effects on stool microbial community composition using 16S rRNA gene amplicon sequencing. The largest source of variability in stool community composition was attributable to inter-individual differences regardless of delivery condition. Although the relative effect of delivery condition on community composition was small compared to inter-individual variability (1.6% vs. 60.5%, permutational multivariate analysis of variance [PERMANOVA]) and temporal variation within subjects over 10 weeks (5.2%), shifts in microbial taxa associated with delivery conditions were non-systematic and subject-specific. These findings indicated that it is not possible to model or accurately predict shifts in stool community composition associated with sampling logistics. Based on our findings, we recommend delivery of fresh, preservative-free stool samples to laboratories within 2 hr either at ambient or chilled temperatures to minimise perturbations to microbial community composition. In addition, subsamples from different fractions of the same stool displayed a small (3.3% vs. 72.6% inter-individual variation, PERMANOVA) but significant effect on community composition. Collection of larger sample volumes for homogenisation is recommended.

Complete Genome Sequences of Six Novel Macaca mulatta Papillomavirus Types Isolated from Genital Sites of Rhesus Monkeys in Hong Kong SAR, China.

The complete genomes of six Macaca mulatta papillomavirus types isolated from genital sites of rhesus monkeys were characterized, and less than 72% identity with the complete L1 genes of known papillomaviruses was found. Macaca mulatta papillomavirus type 2 (MmPV2), MmPV3, and MmPV6 cluster into the genus Alphapapillomavirus, and MmPV4, MmPV5, and MmPV7 cluster into the genus Gammapapillomavirus.

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.

Complete Genome Sequence of a Novel Human Papillomavirus Isolated from Oral Rinse.

A novel human papillomavirus (HPV TG550) isolated from the oral rinse of a Chinese male resident was fully characterized. The L1 open reading frame of HPV TG550 shares 82.5% nucleotide sequence similarity with its closest relative, HPV166, and clusters within the species group Gammapapillomavirus 19.

Ancient Evolution and Dispersion of Human Papillomavirus 58 Variants.

Human papillomavirus 58 (HPV58) is found in 10 to 18% of cervical cancers in East Asia but is rather uncommon elsewhere. The distribution and oncogenic potential of HPV58 variants appear to be heterogeneous, since the E7 T20I/G63S variant is more prevalent in East Asia and confers a 7- to 9-fold-higher risk of cervical precancer and cancer. However, the underlying genomic mechanisms that explain the geographic and carcinogenic diversity of HPV58 variants are still poorly understood. In this study, we used a combination of phylogenetic analyses and bioinformatics to investigate the deep evolutionary history of HPV58 complete genome variants. The initial splitting of HPV58 variants was estimated to occur 478,600 years ago (95% highest posterior density [HPD], 391,000 to 569,600 years ago). This divergence time is well within the era of speciation between Homo sapiens and Neanderthals/Denisovans and around three times longer than the modern Homo sapiens divergence times. The expansion of present-day variants in Eurasia could be the consequence of viral transmission from Neanderthals/Denisovans to non-African modern human populations through gene flow. A whole-genome sequence signature analysis identified 3 amino acid changes, 16 synonymous nucleotide changes, and a 12-bp insertion strongly associated with the E7 T20I/G63S variant that represents the A3 sublineage and carries higher carcinogenetic potential. Compared with the capsid proteins, the oncogenes E7 and E6 had increased substitution rates indicative of higher selection pressure. These data provide a comprehensive evolutionary history and genomic basis of HPV58 variants to assist further investigation of carcinogenic association and the development of diagnostic and therapeutic strategies.IMPORTANCE Papillomaviruses (PVs) are an ancient and heterogeneous group of double-stranded DNA viruses that preferentially infect the cutaneous and mucocutaneous epithelia of vertebrates. Persistent infection by specific oncogenic human papillomaviruses (HPVs), including HPV58, has been established as the primary cause of cervical cancer. In this work, we reveal the complex evolutionary history of HPV58 variants that explains the heterogeneity of oncogenic potential and geographic distribution. Our data suggest that HPV58 variants may have coevolved with archaic hominins and dispersed across the planet through host interbreeding and gene flow. Certain genes and codons of HPV58 variants representing higher carcinogenic potential and/or that are under positive selection may have important implications for viral host specificity, pathogenesis, and disease prevention.