History Of Oral Human Papillomavirus Infection Research Articles

Association of Oral Microbiome With Oral Human Papillomavirus Infection: A Population Study of the National Health and Nutrition Examination Survey, 2009-2012.

Oral human papillomavirus (HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. A cross-sectional analysis of 5496 20-59-year-old participants in the 2009-2012 National Health and Nutrition Examination Survey was performed. Associations with oral HPV infection were assessed using multivariable logistic regression for oral microbiome α-diversity (within-sample diversity), and using principal coordinate analysis and permutational multivariate analysis of variance for β-diversity (between-sample heterogeneity). Overall, for α-diversity, a lower number of observed amplicon sequence variants (adjusted odds ratio [aOR] = 0.996; 95% confidence interval [CI] = .992-.999) and reduced Faith's phylogenetic diversity (aOR = 0.95; 95% CI = .90-.99) were associated with high-risk oral HPV infection. β-diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R2 = 0.054%; P = .029) and unweighted UniFrac distance (R2 = 0.046%; P = .045). There were differential associations when stratified by sex. Both oral microbiome α-diversity and β-diversity were marginally associated with oral HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection.

Natural History of Oral HPV Infection among Indigenous South Australians.

This study aims to describe the natural history of and identify the risk factors associated with oral human papillomavirus (HPV) infections in an Australian Indigenous cohort. A longitudinal cohort study design, with baseline (2018), 12-month, and 24-month data obtained from Indigenous Australians aged 18+ years in South Australia, was performed. Face-to-face interviews were conducted, and saliva samples for HPV testing were collected at each time point. Basic descriptive analyses were conducted to calculate prevalence, incidence, persistence, clearance, and incidence proportions of any HPV infection. Multivariable logistic regression analyses with adjusted prevalence ratios (PRs) were conducted to identify risk factors associated with oral HPV infection. Among 993 participants with valid saliva samples, 44 HPV types were identified. The prevalence of infection with any oral HPV infection was 51.3%, high-risk HPV was 11%, and types implicated in Heck's disease (HPV 13 or 32) was 37.4%. The incidence, persistence, and clearance of any and high-risk HPV infections were 30.7%, 11.8% and 33.3% vs. 9.3%, 2.8%, and 9%, respectively. Our findings indicate that the prevalence, incidence, and persistence of oral HPV infection in a large sample of Indigenous Australians were high, and clearance was low. Oral sex behaviours and recreational drug use were risk factors associated with incident high-risk HPV infection.

Natural history of oral HPV infection: Longitudinal analyses in prospective cohorts from Australia.

Oral infection with human papillomavirus (HPV) is likely to underpin the rapidly rising incidence of oropharyngeal squamous cell carcinoma; however, there are few data describing the natural history of oral HPV infection. We recruited 704 participants aged 20 to 70 years from worksites, universities and primary care practices in Brisbane, Australia. Participants completed questionnaires at baseline, 12 and 24 months and donate four saliva samples at baseline, 6, 12 and 24 months for HPV polymerase chain reaction testing and typing. We estimated the prevalence of oral HPV infection at baseline, incidence of new infections among those HPV-negative at baseline, clearance rate and persistent infections. At baseline, 10.7% of participants had oral HPV infections from 26 different HPV types. Sexual behaviours were associated with oral HPV infection, including more partners for passionate kissing (29 or more; odds ratio [OR] 3.4, 95% confidence interval [CI] 1.5-8.0), and giving and receiving oral sex (16 or more; OR 5.4, 95% CI 1.6-17.7 and OR 5.6, 95% CI 1.6-18.7, respectively). Of 343 participants, HPV-free at baseline and with subsequent saliva samples, 87 (25%) acquired new infections over the 24 months. Sixty-eight of 87 people included in the clearance analysis (78%) cleared their oral HPV infections. Clearance was associated with being a nonsmoker (OR 12.7, 95% CI 1.3-122.8), and no previous diagnosis of a sexually transmitted infection (OR 6.2, 95% CI 2.0-19.9). New oral infections with HPV in this sample were not rare. Although most infections were cleared, clearance was not universal suggesting a reservoir of infection exists that might predispose to oropharyngeal carcinogenesis.

Prevalence and Determinants of Oral Human Papillomavirus Infection in 500 Young Adults from Italy.

Although the prevalence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is increasing in developed countries and becoming a relevant health issue, the natural history of oral HPV infection is still unclear. Estimating the infection’s prevalence in specific populations and identifying risk factors can widen our understanding of its natural history and help to delineate appropriate prevention strategies. This study sought to (i) determine oral HPV prevalence and genotype distribution in a large series of young Italian adults, (ii) validate an oral rinse sampling/storage protocol, and (iii) pinpoint factors associated with oral HPV infection. Five hundred students, nurses, and technicians (19–35 years-old) studying and working at/for the University of Padua were recruited. Each participant was provided with an oral rinse sampling kit and instructions for use. They were also asked to complete an anonymous questionnaire concerning their demographic characteristics and behaviors. The questionnaires and oral rinse containers were labeled with the same identification code number. The oral rinse samples were tested using a bead-based multiplex BSGP5+/6+-MPG genotyping assay which amplifies the L1 region of 51 mucosal HPV types. The prevalence of oral HPV infection was 4.0% (95% confidence interval (CI), 2.5%-6.1%); those of 14 high-risk HPV types and of HPV-type 16 (HPV16) infection were 2.2% (95% CI, 1.1%-3.9%) and 1.6% (95% CI, 0.6%-3.1%), respectively. HPV16 was the most frequent genotype (40.0% of oral HPV infections). No association was found between oral infection and the co-variables studied (gender, tobacco, alcohol and illegal drug use, number of sex and oral sex partners, HPV vaccination status, history of HPV and sexually transmitted infections, abnormal pap smears, recurrent tonsillitis and tonsillectomy). The oral rinse sampling protocol outlined here proved to be simple, efficient and well tolerated, and the prevalence rate can be considered reliable and thus useful to guide future research. Determinants of oral HPV infection are still unclear and further studies are certainly warranted.

Human papillomavirus-related oropharyngeal cancer in the HIV-infected population.

Human papillomavirus (HPV) is a common sexually transmitted virus and an important etiologic factor in head and neck cancers. HIV-infected individuals are at increased risk of developing oropharyngeal cancers (OPC) compared with the general population. HPV-positive OPC are also increasingly a significant cause of morbidity and mortality for HIV-infected individuals in the era of effective combination antiretroviral therapy. The epidemiology and natural history of oral HPV infection have not been well established, but it appears that oral HPV infection is less common than anal infection, and more common among HIV-infected persons than the general population. Prevention of OPC is therefore increasingly important in HIV-infected individuals. Although not demonstrated in randomized controlled trials, HPV vaccination may prevent oral HPV infection as well. The focus of organized HPV cancer prevention programs should include prophylactic HPV vaccination to reduce the burden of high-risk HPV and low-risk HPV types who have not yet been exposed.

Human Papilloma Virus in Oral Squamous Cell Carcinoma - The Enigma Unravelled.

Squamous cell carcinoma of the head and neck (HNSCC) has long been regarded as a disease entity having a remarkable incidence worldwide and a fairly onerous prognosis; thus encouraging further research on factors that might modify disease outcome. Squamous cell carcinomas encompass at least 90% of all oral malignancies. Several factors like tobacco and tobacco-related products, alcohol, genetic predisposition and hormonal factors are suspected as possible causative factors. Human papilloma virus (HPV), the causal agent of cervical cancer also appears to be involved in the aetiology of oral and oropharyngeal cancer. HPVpositive squamous cell carcinoma (SCC) seems to differ from HPV-negative SCC. Many questions about the natural history of oral HPV infection remain under investigation. The aim of this review is to highlight the current understanding of HPV-associated oral cancer with an emphasis on its prognosis, detection and management.

The epidemiology of the human papillomavirus related to oropharyngeal head and neck cancer.

To summarize the epidemiology of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OSCC). Articles in the English language referenced in MEDLINE/PubMed from the year 2000 onward. Relevant articles pertaining to the epidemiology of HPV-related OSCC were selected for review, with a particular preference for articles from 2008 onward. The incidence of HPV-related OSCC continues to increase in North America and Western Europe, with up to 70% of new oropharyngeal cancer cases being attributed to HPV, whereas data from the developing world remain lacking. There is evidence to support distinct risk factors for HPV-related OSCC as compared with HPV-unrelated OSCC. The long-term natural history of HPV infections remains unknown. HPV-related OSCC are associated with an improved prognosis both at the time of primary diagnosis and disease progression. There is preliminary evidence to show that HPV vaccination initiatives are effective in preventing HPV cervical infections, although data related to oral HPV infections are lacking. The epidemiology of HPV-related OSCC is evolving. Further efforts are needed to characterize the natural history of oral HPV infection and its relationship with the eventual development of HPV-associated OSCC to develop effective tools for secondary prevention. NA.

Oral Human Papillomavirus (HPV) Infection in Healthy Individuals and Patients with Head and Neck Squamous Cell Carcinoma (HNSCC)

Human papillomavirus (HPV) infection is the most common sexually transmitted disease. It also contributes significantly to infection-associated human malignancies, including cervical, anal, penile, vaginal, and vulvar cancer as well as a subset of head and neck squamous cell carcinoma (HNSCC). Despite our extensive knowledge on the role of HPV in the etiology of cervical cancer, cervical cancer screening, prevention, and clinical management, we have just begun to appreciate the role of HPV in the tumorigenesis of HNSCC. In this paper, we will review our current knowledge on the natural history of oral HPV infection in the general population, risk factors for oral HPV infection, the presence of novel HPV types infecting oral cavity, limitations of existing methods for oral HPV detection and its application in the clinical setting. Finally, we will also discuss the role of HPV vaccine in preventing HNSCC.

Risk factors for acquisition and clearance of oral human papillomavirus infection among HIV-infected and HIV-uninfected adults.

Human papillomavirus (HPV) causes the majority of oropharyngeal cancers in the United States, yet the risk factors for and natural history of oral HPV infection are largely unknown. In 2010-2011, a US-based longitudinal cohort study of 761 human immunodeficiency virus (HIV)-infected and 469 at-risk HIV-uninfected participants from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study was initiated. Semiannually collected oral rinses were evaluated for 37 HPV genotypes using the Roche LINEAR ARRAY HPV Genotyping Test (Roche Molecular Systems, Pleasanton, California), and factors associated with oral HPV incidence and clearance were explored using adjusted Wei-Lin-Weissfeld modeling. Through 2013, the 2-year cumulative incidence of any type of oral HPV infection was 34% in HIV-infected persons and 19% in HIV-uninfected persons. However, many of these infections cleared. Seven percent of incident infections and 35% of prevalent infections persisted for at least 2 years. After adjustment for other risk factors, HIV infection (adjusted hazard ratio = 2.3, 95% confidence interval: 1.7, 3.2), reduced current CD4 cell count, and increased numbers of oral sex and "rimming" partners increased the risk of incident oral HPV infection, whereas male sex, older age, and current smoking increased the risk of oral HPV persistence (each P < 0.05). This helps explain the consistent associations observed between these factors and prevalent oral HPV infection in previous cross-sectional studies.

Incidence and clearance of oral human papillomavirus infection in men: the HIM cohort study

Oral human papillomavirus (HPV) infection causes a subset of oropharyngeal cancers. These cancers disproportionately affect men, are increasing in incidence, and have no proven prevention methods. We aimed to establish the natural history of oral HPV infection in men. To estimate incidence and clearance of HPV infections, men residing in Brazil, Mexico, and the USA who were HIV negative and reported no history of anogenital cancer were recruited into the HPV Infection in Men (HIM) cohort study. A subset of the cohort who provided two or more oral rinse-and-gargle samples with valid HPV results and who completed a minimum of 2 weeks of follow-up were included in this analysis. Oral rinse-and-gargle samples and questionnaire data were obtained every 6 months for up to 4 years. Samples were analysed for the presence of oncogenic and non-oncogenic HPV infections by the linear array method. 1626 men aged 18-73 years and with a median follow-up of 12·7 months (IQR 12·1-14·7) were included in the analysis. During the first 12 months of follow-up, 4·4% (95% CI 3·5-5·6; n=115 incident infections) of men acquired an incident oral HPV infection, 1·7% (1·2-2·5; n=53 incident infections) an oral oncogenic HPV infection, and 0·6% (0·3-1·1; n=18 incident infections) an oral HPV 16 infection. Acquisition of oral oncogenic HPV was significantly associated with smoking and not being married or cohabiting, but was similar across countries, age groups, and reported sexual behaviours. Median duration of infection was 6·9 months (95 % CI 6·2-9·3; n=45 cleared infections) for any HPV, 6·3 months (6·0-9·9; n=18 cleared infections) for oncogenic HPV, and 7·3 months (6·0-not estimable; n=5 cleared infections) for HPV 16. Eight of the 18 incident oral HPV 16 infections persisted for two or more study visits. Newly acquired oral oncogenic HPV infections in healthy men were rare and most were cleared within 1 year. Additional studies into the natural history of HPV are needed to inform development of infection-related prevention efforts. US National Cancer Institute, Merck Sharp & Dohme.

HPV-associated head and neck cancer: a virus-related cancer epidemic

A rise in incidence of oropharyngeal squamous cell cancer--specifically of the lingual and palatine tonsils--in white men younger than age 50 years who have no history of alcohol or tobacco use has been recorded over the past decade. This malignant disease is associated with human papillomavirus (HPV) 16 infection. The biology of HPV-positive oropharyngeal cancer is distinct with P53 degradation, retinoblastoma RB pathway inactivation, and P16 upregulation. By contrast, tobacco-related oropharyngeal cancer is characterised by TP53 mutation and downregulation of CDKN2A (encoding P16). The best method to detect virus in tumour is controversial, and both in-situ hybridisation and PCR are commonly used; P16 immunohistochemistry could serve as a potential surrogate marker. HPV-positive oropharyngeal cancer seems to be more responsive to chemotherapy and radiation than HPV-negative disease. HPV 16 is a prognostic marker for enhanced overall and disease-free survival, but its use as a predictive marker has not yet been proven. Many questions about the natural history of oral HPV infection remain under investigation. For example, why does the increase in HPV-related oropharyngeal cancer dominate in men? What is the potential of HPV vaccines for primary prevention? Could an accurate method to detect HPV in tumour be developed? Which treatment strategies reduce toxic effects without compromising survival? Our aim with this review is to highlight current understanding of the epidemiology, biology, detection, and management of HPV-related oropharyngeal head and neck squamous cell carcinoma, and to describe unresolved issues.

Six‐month natural history of oral versus cervical human papillomavirus infection

Human papillomavirus (HPV) infection is etiologically associated with a subset of oral cancers, and yet, the natural history of oral HPV infection remains unexplored. The feasibility of studying oral HPV natural history was evaluated by collecting oral rinse samples on 2 occasions at a 6-month interval from 136 HIV-positive and 63 HIV-negative participants. Cervical vaginal lavage samples were concurrently collected for comparison. HPV genomic DNA was detected in oral and cervical samples by consensus primer PCR and type-specified for 37 HPV types. The six-month cumulative prevalence of oral HPV infection was significantly less than for cervical infection (p < 0.0001). HIV-positive women were more likely than HIV-negative women to have an oral (33 vs. 15%, p = 0.016) or cervical (78 vs. 51%, p < 0.001) infection detected. Oral HPV infections detected at baseline were as likely as cervical infections to persist to 6 months among HIV-negative (60% vs. 51%, p = 0.70) and HIV-positive (55% vs. 63%, p = 0.27) women. Factors that independently elevated odds for oral HPV persistence differed from cervical infection and included current smoking (OR = 8, 95% CI = 1.3-53), age above 44 years (OR = 20, 95% CI = 4.1-83), CD4 < 500 (OR = 6, 95% CI = 1.1-26), use of HAART therapy (OR = 12, 95% CI = 1.0-156), and time on HAART therapy (trend p = 0.04). The rate of oral HPV infections newly detected at follow-up was significantly lower than cervical infection among HIV-positive (p < 0.001) and HIV-negative women (p < 0.001). Our study not only demonstrates that it is feasible to study the natural history of oral HPV infection with oral rinse sampling, but also indicates that oral and cervical HPV natural history may differ.

PL7 Oral viral infections that could be transmitted oro‐genitally

Orogenital transmission has been suggested for several viruses, e.g. herpes simplex virus‐1 and ‐2 (HS‐1 and HSV‐2), Epstein‐Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus‐8 (HHV‐8), human papillomavirus (HPV) and HIV. Most studies have focused on HIV, HSV and HPV. Unprotected orogenital contact, especially receptive oral intercourse, is associated with greater risk of HIV transmission than previously thought. Factors potentially associated with increased risk of HIV transmission through oral sex include poor oral health, the salivary anti‐HIV properties such as peroxidases and thrombospondin‐1, the local and systemic immunological responses, concomitant sexually transmitted infections, ejaculation in the mouth, local mucosal integrity, and the level of infectious HIV present at the oral mucosa. The probability of per act transmission in oral intercourse with ejaculation is 0.04%. HSV‐2 has been regarded as a sexually transmitted virus while HSV‐1 is causing primary herpetic gingivo‐stomatitis, muco‐cutaneous oro‐facial disease and ocular disease. Also HSV‐2 might be detected occasionally in oro‐facial area. Recent data on young women with a primary genital infection indicate that HSV‐1 is much more frequent than HSV‐2. Oro‐genital route of transmission is more common than expected in genital HSV‐1 infections. EBV is a tumorigenic herpes virus that is carried as a persistent infection by more than 90% of adults. Most persistently infected people produce EBV in their saliva, and transmission is through close contact. There is a significant association between sexual intercourse and EBV seropositivity, increasing with numbers of sex partners. Because EBV has been found in genital secretions from healthy seropositive men and women, direct spread of virus during sexual intercourse is possible. Today, 106 HPV types have been sequenced of which almost 40 have been detected also in oral mucosa, causing benign epithelial lesions (papillomas, condylomas, warts and focal epithelial hyperplasia, or FEH). Recent meta‐analyses of the case‐control studies have confirmed HPV as an independent risk factor for oral SCC with odds ratios (OR) 3.7 to 5.4. HPV16 is the overwhelmingly most frequent type. HPV has been regarded as a sexually transmitted disease but this view is challenged by frequent detection of HPV in children. Unlike in genital tract, natural history of oral HPV infection is poorly studied. As part of the Finnish HPV Family Study we evaluated natural history of oral HPV in within family members. The detection rate of HR HPVs varied from 15% to 27%. Our results indicate that natural history of HPV infection in oral mucosa mimics that of genital HPV infections. Oral sex had no association to oral HPV infection, but a persistent oral HPV infection of the spouse increased the risk of persistent oral HPV infection in the other spouse 10‐fold.