Oral Human Papillomavirus DNA Research Articles

Human polyomavirus BKPyV and JCPyV serostatus has no impact on women´s human papillomavirus infection outcome.

Polyomaviruses have both structural and functional similarities with papillomaviruses. Accordingly, their role in human papillomavirus (HPV) associated malignancies has been studied with conflicting results. Our goal was to disclose any association between BK (BKPyV) and/or JC (JCPyV) polyomavirus serology and HPV data derived from Finnish women (327) in a 6-year prospective follow-up. Glutathione S-transferase fusion-protein-capture (ELISA) in combination with fluorescent bead technology was used to analyze antibodies to BKPyV and JCPyV. In the longitudinal setting, BKPyV or JCPyV serostatus was related to i) oral- and ii) genital low (LR)- and high risk (HR) HPV DNA detection, iii) HPV16 persistence at both these sites, iv) results of the Pap (Papanicolaou) smear taken at baseline, and v) development of incident CIN (cervical intraepithelial neoplasia) during the follow-up. Being BKPyV or JCPyV seropositive was not significantly associated with HPV seropositivity to either LR- or HR-genotypes, genital- or oral HPV DNA positivity, persistence of genital- or oral HPV16 infection, grade of Pap smear, or development of incident CIN. Thus, the present study could not provide any confirmation to the concept that co-infections by HPyV and HPV have interactions that impact on the clinical manifestations or outcomes of HPV infections either in the genital tract or in the oral mucosa.

Prevalence of oral and blood oncogenic human papillomavirus biomarkers among an enriched screening population: Baseline results of the MOUTH study.

Human papillomavirus (HPV)-related oropharyngeal cancer screening is being explored in research studies, but strategies to identify an appropriate population are not established. The authors evaluated whether a screening population could be enriched for participants with oncogenic HPV biomarkers using risk factors for oral HPV. Participants were enrolled at Johns Hopkins Hospitals and Mount Sinai Icahn School of Medicine. Eligible participants were either men aged 30 years or older who had two or more lifetime oral sex partners and a personal history of anogenital dysplasia/cancer or partners of patients who had HPV-related cancer. Oral rinse and serum samples were tested for oncogenic HPV DNA, RNA, and E6 or E7 antibodies, respectively. Participants with any biomarker were considered at-risk. Of 1108 individuals, 7.3% had any oncogenic oral HPV DNA, and 22.9% had serum antibodies for oncogenic HPV E6 or E7. Seventeen participants (1.5%) had both oral and blood biomarkers. HPV type 16 (HPV16) biomarkers were rarer, detected in 3.7% of participants, including 20 with oral HPV16 DNA and 22 with HPV16 E6 serum antibodies (n=1 had both). In adjusted analysis, living with HIV (adjusted odds ratio, 2.65; 95% CI, 1.60-4.40) and older age (66-86 vs. 24-45years; adjusted odds ratio, 1.70; 95% CI, 1.07-2.70) were significant predictors of being at risk. Compared with the general population, the prevalence of oral HPV16 (1.8% vs. 0.9%), any oncogenic oral HPV DNA (7.3% vs. 3.5%), and HPV16 E6 antibodies (2.2% vs. 0.3%) was significantly elevated. Enrichment by the eligibility criteria successfully identified a population with higher biomarker prevalence, including HPV16 biomarkers, that may be considered for screening trials. Most in this group are still expected to have a low risk of oropharyngeal cancer.

Stepped Behavioral and Biological Screening for Oral Oncogenic HPV DNA in Middle-aged and Elderly Adults: A Feasibility Study.

Novel preventive interventions are needed to address the rising incidence of HPV+ OPC. In this feasibility study, we characterized barriers to a two-step, behavioral and biological screening program for oral oncogenic HPV infection, an intermediate outcome for HPV+ OPC.

Association between self-reported periodontitis and high-risk oral human papillomavirus infection among Indigenous South Australians: A cross-sectional study.

IntroductionThe incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing globally, reflecting an increase in human papillomavirus (HPV)-related lesions. Indigenous populations are disproportionately affected by OPSCCs. Currently, testing for oral HPV is not recommended as a screening tool to permit early detection of OPSCCs due to the high population prevalence of HPV infection. Periodontitis may be a marker of oral HPV infection, but previous research evaluating this association has been inconclusive. Here we report a large population-based study examining the association between high-risk oral HPV infection and periodontitis among Indigenous South Australians.MethodsWe utilised a large convenience sample of Indigenous South Australians aged 18+ years recruited between February 2018 and February 2020. Of the original cohort (n = 1011), 748 (73.9%) participants participated in the 12 month follow-up. Detailed information on sociodemographic characteristics, health-related behaviours, and sexual history were collected at enrolment. Saliva samples were collected at 12 months and tested for the presence of oral HPV DNA using the optimized general primer (GP) + PCR system. The primary outcomes were the prevalence of any high-risk oral HPV DNA, and separately, HPV 16 and/or 18. Periodontitis was assessed at follow-up by using validated self-reported periodontitis screening questions. Logistic regression analyses were undertaken to assess the association between self-reported periodontitis and oral HPV infection with adjustment for potential sociodemographic and behavioural confounders, with estimates presented as odds ratios (OR) and 95% confidence interval (CI).ResultsData on 673 participants (89.9% of the follow-up cohort) were available. Participants ranged in age from 18 to 80 (mean age 42.2, SD 14.7) and 31.5% were male. Overall, 115 (17.1%) participants had self-reported periodontitis, 40 (5.9%) had any high-risk oral HPV and 14 (2.1%) had HPV 16 and/or 18. Any high-risk HPV was detected among seven (17.5%) participants and HPV 16 and/or 18 was detected in three (21.4%) who self-reported periodontitis. In the regression analyses no significant association was found between self-reported periodontitis and high-risk oral HPV (adjusted OR: 1.10; 95% CI: 0.45–2.70) or HPV 16 and/or 18 (adjusted OR: 1.27; 95% CI: 0.32–5.03).ConclusionThis study did not find any association between self-reported periodontitis and high-risk oral HPV among Indigenous South Australians. Further targeted studies with standardized clinical measures of periodontal disease are needed to clarify the link between high-risk oral HPV and periodontal disease. If confirmed this would add further weight to the importance of recommendations about the utility of periodontitis screening to identify individuals at risk of carrying high-risk oral HPV, who may benefit from more intensive screening and ongoing monitoring.

Performance of oral HPV DNA, oral HPV mRNA and circulating tumor HPV DNA in the detection of HPV-related oropharyngeal cancer and cancer of unknown primary.

A biomarker that is useful for the detection of human papillomavirus (HPV)‐related oropharyngeal cancer (OPC) and cancer of unknown primary (CUP) is indispensable. We evaluated the diagnostic performance of HPV DNA and mRNA in oral gargle samples and circulating tumor HPV16 DNA (ctHPV16DNA) in blood samples. Oral HPV DNA and mRNA were analyzed using commercially available HPV assays of the GENOSEARCH HPV31 and Aptima, respectively. ctHPV16DNA was analyzed using in‐house droplet digital polymerase chain reaction. Seventy‐four patients with OPC and eight patients with CUP were included. The sensitivity and specificity of oral HPV DNA, oral HPV mRNA, and ctHPV16DNA were 82% (95% confidence interval [CI] = 66‐92) and 100% (95% CI = 88‐100), 85% (95% CI = 69‐94) and 94% (95% CI = 73‐100), and 93% (95% CI = 81‐99) and 97% (95% CI = 84‐100), respectively, for HPV16‐related OPC, while those were 20% (95% CI = 1‐72) and 100% (95% CI = 3‐100), 0% (95% CI = 0‐52) and 100% (95% CI = 3‐100), and 100% (95% CI = 54‐100) and 100% (95% CI = 16‐100), respectively, for HPV16‐related CUP. The sensitivity of ctHPV16DNA for HPV16‐related OPC was higher than that of oral biomarkers, though the difference was not statistically significant. ctHPV16DNA remarkably correlated with the anatomic extent of disease, total metabolic tumor volume and HPV16 copy number per tumor genome in patients with HPV16‐related OPC/CUP, whereas oral biomarkers did not. In conclusion, ctHPV16DNA is a potentially promising biomarker for HPV16‐related OPC, while further studies are required for HPV16‐related CUP.

Oral secretory leukocyte protease inhibitor (SLPI): Associations with oropharyngeal cancer and treatment outcome.

BackgroundRates of oropharyngeal cancer (OPC) associated with alcohol & tobacco use have decreased, while human papillomavirus (HPV) associated OPC has increased among men in the US. Secretory leukocyte protease inhibitor (SLPI), detectable in a variety of secretions, has been implicated in cancers of the head and neck, associated with tumor progression and anti-viral activity. Using the recently verified oral gargle specimen, this study aimed to assess the association of salivary SLPI expression with risk of OPC and response to treatment.MethodsA case-control study design compared levels of salivary SLPI among OPC cases to age and tobacco smoking matched healthy controls. Oral HPV DNA and SLPI was quantified from oral gargle specimens. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for associations of oral SLPI and risk of OPC and treatment outcomes.ResultsIn crude and adjusted analyses of 96 OPC cases and 97 age- and smoking-matched controls, OPC was not significantly associated with oral gargle SLPI levels. Among cases, oral SLPI was associated with tonsillectomy (p = 0.018) and among controls oral SLPI was associated with HPV in the oral gargle (p = 0.008). Higher concentrations of SLPI was significantly associated with increased odds of incomplete treatment response (T2: OR: 12.39; 95% CI: 1.44–106.72; T3: OR: 9.86; 95% CI: 1.13–85.90) among all cases, but not among P16+ cases.ConclusionsSalivary SLPI was not associated with OPC risk but was associated with higher odds of an incomplete treatment response.

Relationship between the prevalence of oral human papillomavirus DNA and periodontal disease (Review).

Human papillomavirus (HPV) is a small DNA virus that infects the basal keratinocytes of squamous epithelium in the skin, and in the oral and genital mucosa. Smoking and sexual behavior have been recognized as significant risk factors for oral HPV infection. In the present review, the findings of recent studies of oral HPV infection in relation to periodontitis are discussed, as well as periodontopathic bacteria and periodontal herpes virus. Previous research suggests that HPV localizes to the inflammatory periodontal tissue. Inflammatory periodontal pockets may thus act as a reservoir for HPV. The interactions between HPV and periodontopathic bacteria remain unclear, but it is hypothesized that oral HPV infection may be related to a characteristic oral microbiome. Smoking is associated with HPV and periodontitis, as smoking induces destruction of periodontal tissue and suppresses the host defense, allowing HPV to infect periodontal tissue. Carcinogenic HPV and periodontitis may lead to the development of oral cavity cancer. However, oral HPV E6/E7 expression (transcriptionally active HPV) has not yet been fully investigated in patients with periodontitis. Collectively, the evidence suggests that oral HPV prevalence may be associated with periodontitis. The effect of clinical factors (age, sex, smoking, immunosuppressive condition and vaccination) on oral HPV DNA prevalence should be considered when clarifying the relationship between oral HPV and periodontitis. Additionally, the sampling method should be carefully chosen to directly detect HPV DNA in periodontal tissues.

Interferon-γ and IL-5 associated cell-mediated immune responses to HPV16 E2 and E6 distinguish between persistent oral HPV16 infections and noninfected mucosa.

ObjectivesNatural history of human papillomavirus (HPV) infection in the head and neck region is poorly understood, and their impact on collective HPV‐specific immunity is not known.Materials and methodsIn this study, we have performed a systematic analysis of HPV16‐specific cell‐mediated immunity (CMI) in 21 women with known oral and genital HPV DNA status and HPV serology (Ab) based on 6‐year follow‐up data. These women being a subgroup from the Finnish Family HPV Study were recalled for blood sampling to be tested for their CMI‐responses to HPV16 E2, E6, and E7 peptides.ResultsThe results showed that HPV16 E2‐specific lymphocyte proliferation was more prevalent in women who tested HPV16 DNA negative in oral mucosa and were either HPV16 seropositive or negative than in HPV16 DNA+/Ab+ women (p = 0.046 and p = 0.035). In addition, the HPV16 DNA−/Ab− women most often displayed E6‐specific proliferation (p = 0.020). Proportional cytokine profiles indicated that oral HPV16‐negative women were characterized by prominent IFN‐γ and IL‐5 secretion not found in women with persisting oral HPV16 (p = 0.014 and p = 0.040, respectively).ConclusionsOur results indicate that the naturally arising immune response induced by oral HPV infections displays a mixed Th1/Th2/Th17 cytokine profile while women with persisting oral HPV16 might have an impaired HPV16‐specific CMI, shifted partly toward a Th2 profile, similarly as seen earlier among patients with high‐grade genital HPV lesions. Thus, the lack of HPV 16 E2 and E6 specific T memory cells and Th2 cytokines might also predispose women for persistent oral HPV16 infection which might be related to the risk of cancer.

The prevalence and risk-factors of oral HPV DNA detection among HIV-infected men between men who have sex with men and heterosexual men

Background Human papillomavirus (HPV)-associated oropharyngeal carcinomas are becoming more common with epidemiological impact on human immunodeficiency virus (HIV)- positive individuals. Objective: We evaluated prevalence and risk factors for oral HPV DNA among HIV-infected men who have sex with men (MSM) or heterosexual men. Methods: This cross-sectional hospital-based study included 255 HIV-infected men with different sexual orientation 142 MSM and 113 heterosexual men, who answered a self-administered questionnaire on sociodemographic, clinical and behavioural data. Oral swab and mouthwash samples were analysed by polymerase chain reaction and genotyped by AnyplexTM II 28 (Seegene®). Results: Oral HPV was detected in 17.6% (95% Confidence Interval (CI) 13.5–22.8%), 17.6% in MSM and 17.7% in heterosexual men (p = .984). Multiple HPV infections were detected in 86.7% of HPV-positive men. HPV 56 (13.7%) was the most prevalent high-risk genotype, HPV 66 (7.8%) and HPV 70 (12.3%) were the most prevalent probable HR and low-risk HPV genotypes (12.3% and 7.1%, respectively). At multivariable analysis models, oral HPV was associated with >100 lifetime sexual partners (Odds Ratio (OR) 3.73; 95% CI 1.42–9.77) or lifetime tongue-kissing partners (OR 3.20; 95% CI 1.22–8.39) and lower education level (OR 2.90; 95% CI 1.08–7.78 and 2.74; 95% CI 1.04–7.27, respectively). Conclusions: Oral HPV prevalence was similar between HIV-infected MSM and heterosexual men. Oral HPV was associated with lifetime sexual partners, lifetime tongue-kissing partners and being undergraduate, independently of sexual orientation.

Cervical and oral human papillomavirus infection in women living with human immunodeficiency virus (HIV) and matched HIV-negative controls in Brazil

BackgroundDespite the demonstrated role of human Papillomavirus (HPV) in the etiology of cervical cancer and the strong evidence suggesting the importance of HPV in the development of oropharyngeal cancer, several aspects of the interrelationship between HPV infection in both body sites remain unknown, specifically in female human immunodeficiency virus (HIV)-positive (HIV+) patients. We aimed to assess the prevalence, distribution, and concordance of cervical and oral HPV in HIV+ women and matched HIV-negative (HIV-) controls in Brazil.Material and methodsCervical and endocervical samples for cytological screening and HPV detection and oral samples were collected from 115 HIV+ women using highly active antiretroviral therapy (HAART) and 139 HIV-matched controls (HIV-) in Maringá City, Brazil. Risk factors were assessed using a standardized questionnaire, and the data regarding HIV infection were obtained from the patients’ medical records. HPV detection and typing were performed using the Kit Multiplex XGEN Multi HPV Chip HS12.ResultsHIV infection was well controlled in this cohort, but women who exhibited detectable HIV loads were significantly associated with HPV-positive status overall (P = 0.03) and in cervical mucosa (P = 0.01). HIV+ women had significantly more abnormal cytological findings (P = 0.04) than HIV- women. Of the 115 HIV+ women, 48.7% were positive for cervical and/or oral HPV DNA; of the 139 HIV- women, 41% were positive for cervical and/or oral HPV (P = 0.25). Both HIV+ and HIV- women had a statistically higher prevalence of cervical HPV infection than oral infection. The concurrent HPV infection in two anatomical sites was similar in HIV+ and HIV- women; however, HPV type concordance was not observed. HPV type distribution was different between the anatomical sites in both groups, and HIV+ women presented less common types, mainly in oral mucosa.ConclusionOur data support the importance of testing HPV infection in HIV+ women, even when the HIV infection is well controlled. Prospective studies are required to better understand the natural history of HPV infection in both anatomical sites, specifically in HIV+ women.

Association of Oral Human Papillomavirus DNA Persistence With Cancer Progression After Primary Treatment for Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

Detection of persistent oral human papillomavirus (HPV) DNA may be associated with recurrence of HPV-positive head and neck squamous cell carcinoma (HNSCC). To evaluate the dynamics of oral HPV DNA detection and associations with disease outcomes in patients with HPV-positive and HPV-negative HNSCC. This prospective, 2-institution, tertiary referral center study of 396 patients with newly diagnosed oral cavity or oropharyngeal HNSCC was performed from July 11, 2011, to May 7, 2016. Oral rinse samples were prospectively collected at diagnosis and at completion of primary therapy. Weekly oral rinse samples were collected during radiotherapy. Purified tumor and oral rinse sample DNA were evaluated for 37 HPV types, and viral load was quantified by type-specific real-time polymerase chain reaction. Cancers were stratified by tumor HPV status, and HPV was classified as tumor type if identical to that detected in the tumor or nontumor type. Prevalence of HPV DNA before, during, and after therapy. Associations between tumor-type and nontumor-type oral HPV DNA detection and recurrence-free and overall survival were evaluated. Of the 396 patients (median age, 59 years [range, 19-96 years]; 295 [74.5%] men; and 354 [89.4%] white race/ethnicity), 217 had oropharyngeal cancer; 170, oral cavity cancer; and 9, unknown primary HNSCC. The prevalence of oral HPV detection at diagnosis was higher among patients with HPV-positive compared with HPV-negative HNSCC (24 of 194 [84.2%] vs 170 of 202 [12.4%]; P < .001). Oral HPV-16 DNA had an 81% sensitivity and 100% specificity for HPV-16-positive HNSCC. The prevalence and load of tumor-type HPV decreased significantly during primary therapy with odds ratio for probability of infection with each increasing month after diagnosis (0.41; 95% CI, 0.33-0.52; P < .001), whereas those of nontumor types did not (1.01; 95% CI, 0.97-1.06; P = .62). Current smoking was significantly associated with a reduced clearance of tumor-type HPV DNA (hazard ratio [HR], 0.54; 95% CI, 0.32-0.93). Two-year overall survival was significantly lower among the HPV-positive patients with persistent detection of tumor-type HPV after therapy than among those without detectable tumor-type DNA after therapy (68% vs 95%; adjusted HR, 6.61; 95% CI, 1.86-23.44; P = .003), as was recurrence-free survival (55% vs 88%; adjusted HR, 3.72; 95% CI, 1.71-8.09; P < .001). No associations were observed for nontumor type HPV DNA among patients with HPV-positive or HPV-negative HNSCC. Prevalence and viral load of tumor-type HPV DNA decreased rapidly with therapy, and persistent detection was associated with increased risk of recurrence and death. Analysis of tumor type HPV DNA has considerable promise as a biomarker for treatment response and risk of progression.

High Prevalence of Human Papillomavirus on Anal and Oral Samples from Men and Women with External Anogenital Warts: The HERCOLES Study.

Human papillomavirus (HPV) infection is highly prevalent in the sexually active population. This study estimates the prevalence of HPV DNA in anal and oral samples from a cohort of men and women with incident anogenital warts. Anal and/or oral samples from 541 patients with anogenital warts were tested for 35 HPV genotypes using a PCR assay. The overall prevalence of anal HPV and oral HPV DNA was 59.9% (n = 305/509; 95% confidence interval (CI) 55.6-64.1%) and 14.5% (n = 78/538; 95% CI 11.8-17.7%), respectively. Among patients with perianal warts, the anal HPV DNA prevalence was 92.3% (95% CI 87.0-95.5%). Anal HPV DNA prevalence in patients with genital warts but no perianal warts was 55.7% (95% CI 50.6-60.7%). Both anal and oral HPV infections were more common in men who have sex with men than in heterosexual men (90.4% versus 38.5% and 20.8% versus 11.8%, respectively). Anal high risk-HPV infection was more common in women (58.8%) and in men who have sex with men (67.7%). We found that anogenital warts represent a clinical marker for both anal and oral HPV infections, including anal high risk-HPV infections, particularly among women and men who have sex with men.

Population-Wide Associations between Common Viral Pathogens and Self-Reported Arthritis: NHANES 2009-2012.

Objective Persistent infectious agents have been implicated in chronic and recurrent inflammation, which may trigger or worsen many types of arthritis. Our objective was to determine whether exposure to herpes simplex virus (HSV) and human papillomavirus (HPV) is associated with self-reported arthritis among US adults. Methods We used data from two consecutive cycles of the National Health and Nutrition Examination Survey (NHANES) from 2009 until 2012 (N of examined adults ages 20-69 = 9483). Participants were classified as having arthritis by self-report. Viral serology for HSV-1 and HSV-2 and HPV PCR studies from oral rinse and vaginal swabs were available for analysis. We compared HSV-1 and HSV-2 seropositivity as well as oral and vaginal HPV DNA positivity between participants with self-reported arthritis vs. those without, adjusting for age, gender, race, income, education, BMI, and the use of immunosuppressive medications. We used three comparator outcomes, gout, kidney stones, and hypertension, to evaluate whether the associations were specific or not to arthritis. Results Arthritis was associated with older age, female gender, non-Hispanic White and Non-Hispanic Black race, higher BMI, and lower socioeconomic status. HSV-2 seropositivity, but not HSV-1 seropositivity, was independently associated with arthritis after adjustment for age, gender, race, income, education, BMI, and the use of immunosuppressive medications: AOR 1.48 (1.10-1.99). Oral HPV DNA positivity was also independently associated with arthritis: AOR 1.63 (1.17-2.28). After adjustment, there was no statistically significant difference in vaginal HPV DNA positivity between those with vs. those without arthritis: AOR 1.22 (0.90-1.66). There were no significant associations between viral exposures and any of the comparator outcomes. Conclusions HSV-2 seropositivity and oral HPV DNA positivity were associated with self-reported arthritis and not with comparator outcomes, after adjustment for multiple potential confounders. These findings should be confirmed in longitudinal studies.

Understanding personal risk of oropharyngeal cancer: risk-groups for oncogenic oral HPV infection and oropharyngeal cancer

BackgroundIncidence of human papillomavirus (HPV)-related oropharyngeal cancer is increasing. There is interest in identifying healthy individuals most at risk for development of oropharyngeal cancer to inform screening strategies. Patients and methodsAll data are from 2009 to 2014, including 13 089 people ages 20–69 in the National Health and Nutrition Examination Survey (NHANES), oropharyngeal cancer cases from the Surveillance, Epidemiology, and End Results (SEER 18) registries (representing ∼28% of the US population), and oropharyngeal cancer mortality from National Center for Health Statistics (NCHS). Primary study outcomes are (i) prevalence of oncogenic HPV DNA in an oral rinse and gargle sample, and (ii) incident oropharyngeal squamous cell cancer. ResultsOncogenic oral HPV DNA is detected in 3.5% of all adults age 20–69 years; however, the lifetime risk of oropharyngeal cancer is low (37 per 10 000). Among men 50–59 years old, 8.1% have an oncogenic oral HPV infection, 2.1% have an oral HPV16 infection, yet only 0.7% will ‘ever’ develop oropharyngeal cancer in their lifetime. Oncogenic oral HPV prevalence was higher in men than women, and increased with number of lifetime oral sexual partners and tobacco use. Men who currently smoked and had ≥5 lifetime oral sexual partners had ‘elevated risk’ (prevalence = 14.9%). Men with only one of these risk factors (i.e. either smoked and had 2–4 partners or did not smoke and had ≥5 partners) had ‘medium risk’ (7.3%). Regardless of what other risk factors participants had, oncogenic oral HPV prevalence was ‘low’ among those with only ≤1 lifetime oral sexual partner (women = 0.7% and men = 1.7%). ConclusionsScreening based upon oncogenic oral HPV detection would be challenging. Most groups have low oncogenic oral HPV prevalence. In addition to the large numbers of individuals who would need to be screened to identify prevalent oncogenic oral HPV, the lifetime risk of developing oropharyngeal caner among those with infection remains low.

The Natural History of Oral Human Papillomavirus in Young Costa Rican Women.

Oral human papillomavirus (HPV) infection and related oropharyngeal cancer are uncommon in lower-income countries, particularly compared to HPV-associated cervical cancer. However, little is known about the natural history of oral HPV in less-developed settings and how it compares to the natural history of cervical HPV. Three hundred fifty women aged 22 to 33 years from the Costa Rica Vaccine Trial provided exfoliated cells from the cervical and oral regions at 2 visits 2 years apart. Samples from both visits were tested for 25 characterized α HPV types by the SPF10 PCR-DNA enzyme immunoassay-LiPA25 version 1 system. Risk factors for oral HPV persistence were calculated utilizing generalized estimating equations with a logistic link. Among the 82 women with characterized α oral HPV DNA detected at baseline, 14 persisted and were detected 2 years later (17.6%; 95% confidence interval [CI], 10.9-28.5%) and was similar to the persistence of α cervical HPV (40/223; 17.7%; 95% CI, 13.1-23.9%; P = 0.86). Acquisition of new α oral HPV type was low; incident infection (1.7%; 95% CI, 0.6-3.7%). Oral HPV DNA is uncommon in young women in Latin America, and often appears to clear within a few years at similar rates to cervical HPV.

Oral human papillomavirus infection incidence and clearance: a systematic review of the literature.

Subclinical oral human papillomavirus (HPV) infection that persists for decades is likely to precede an HPV-driven squamous cell carcinoma of the head and neck, but little is known about the natural history of oral HPV. We systematically reviewed and abstracted data from nine manuscripts that examined human immunodeficiency virus-negative and cancer-free subjects for oral HPV DNA to determine the pooled baseline prevalence and incidence of newly acquired oral HPV infections, and specifically for HPV-16. We also documented the clearance rate and the median time to clearance, where data existed. Of 3762 individuals, 7.5 % had an oral infection with any HPV type (1.6 % for HPV-16). Meta-regression analysis estimated the 12-month cumulative incidence to be 4.8 % (95 % confidence interval 3.2-7.3 %). The overall oral HPV clearance was reported to be 0-80 % between studies, and the median time to clearance from 6.5 to 18 months. Oral HPV-16 clearance was 43-83 %, and median time to clearance for HPV-16 was 7-22 months. Oral HPV prevalence, incidence and clearance vary considerably between published studies from different geographical regions. Further research is required to identify predictors of persistent oral HPV infection. Measurable baseline prevalence was observed in all studies, as well as non-trivial incidence of newly acquired oral HPV infections and incomplete clearance.

Concordance of Penile and Oral Human Papillomavirus Infections Among Men in the United States

This study examined the concordance of penile and oral human papillomavirus (HPV) infections in the United States. A total of 1683 men aged 18-59 years who participated in the 2013-2014 National Health and Nutrition Examination Survey and had results of oral and penile HPV DNA testing were examined. The prevalence of any HPV genotype was 45.3% on the penis, 11.2% in the oral cavity, and 8.8% at both sites. The prevalence of HPV in the oral cavity was higher among those with than among those without penile HPV infection (19.3% vs 4.4%; prevalence ratio, 4.37 [95% confidence interval, 2.66-7.16]). The prevalence of ≥1 genotype-concordant HPV infection was 3.2% and was associated with sexual behavior, independent of demographic characteristics and smoking status. Sexual behavior may partly explain the observed association between penile and oral HPV infections.

The association of medication use with clearance or persistence of oral HPV infection.

Persistent oral human papillomavirus (HPV) infection increases risk for oropharyngeal carcinoma, and people living with HIV have higher rates of oral HPV infection and related cancers. Some prescription medications have immunomodulatory effects, but the impact of medication use on oral HPV natural history is unknown. Scope® oral rinse-and-gargle samples were collected semi-annually from 1,666 participants and tested for 37 types of oral HPV DNA using PCR; 594 HPV-infected participants with 1,358 type-specific oral HPV infections were identified. Data were collected on recent (past 6months) use of medications. The relationship between medication use and oral HPV clearance was evaluated using Wei-Lin-Weissfeld regression, adjusting for biologic sex, prevalent versus incident infection, age, HIV status and CD4+T cell count. Out of 11 medications examined, oral HPV clearance was significantly reduced in participants reporting recent use of antipsychotics (HR 0.75, 95% CI 0.57-0.99), anxiolytics/sedatives (HR 0.78, 95% CI 0.63-0.96) and antidepressants (HR 0.82, 95% CI 0.67-0.999). Among antipsychotics users, effect modification by HIV status was observed, with reduced clearance in HIV-infected (HR 0.67, 95% CI 0.49-0.91), but not HIV-uninfected participants (p-interaction=0.009). After adjusted analysis, antipsychotic use remained significantly associated with reduced oral HPV clearance overall (aHR 0.75, 95% CI 0.57-0.99), and when restricted to only HIV-infected participants (aHR 0.66, 95% CI 0.48-0.90). After adjustment, anxiolytic/sedative use and antidepressant use were no longer significantly associated with reduced oral HPV clearance. Some medications were associated with decreased oral HPV clearance, most notably antipsychotic medications. These medications are prescribed for conditions that may have immunomodulating effects, so characteristics of underlying illness may have partially contributed to reduced oral HPV clearance.

Oral Human Papillomavirus Infection in Men Who Have Sex with Men: A Systematic Review and Meta-Analysis.

BackgroundThe epidemiology of oral human papillomavirus (HPV) infection in men who have sex with men (MSM) differs from anogenital HPV infection. The impact of HPV vaccination has, to date, largely focussed on anogenital outcomes. Vaccination of MSM in the UK has been recommended and, if implemented, baseline estimates of oral HPV prevalence will be useful.MethodsWe searched Medline, Embase and psycINFO databases for studies reporting prevalence, incidence, and clearance of oral HPV infection in MSM. We performed a random-effects meta-analysis and meta-regression on prevalence estimates and summarised within-study risk factors for oral HPV DNA detection and incidence/clearance rates. We also performed a meta-analysis of the effect of MSM on oral HPV prevalence compared to heterosexual men.Results26 publications were identified. The pooled prevalence of oral HPV16 from twelve estimates was 3.0% (95%CI 0.5–5.5) in HIV-negative and 4.7% (95%CI 2.1–7.3) in HIV-positive MSM. Median age of study participants explained 38% of heterogeneity (p<0.01) in HPV prevalence estimates (pooled = 17% and 29% in HIV-negative and HIV-positive, respectively; 22 estimates). Nine studies compared MSM to heterosexual men and found no difference in oral HPV prevalence (pooled OR 1.07 (95%CI 0.65–1.74)). The clearance rate was higher than incidence within studies. Type-specific concordance between oral and anogenital sites was rare.ConclusionThere was substantial heterogeneity between estimates of oral HPV prevalence in MSM populations that was partly explained by HIV status and median age.

Human papillomavirus infection in the oral cavity of HIV patients is not reduced by initiating antiretroviral therapy.

Objective:The incidence of human papillomavirus (HPV)-related oral malignancies is increasing among HIV-infected populations, and the prevalence of oral warts has reportedly increased among HIV patients receiving antiretroviral therapy (ART). We explored whether ART initiation among treatment-naive HIV-positive adults is followed by a change in oral HPV infection or the occurrence of oral warts.Design:Prospective, observational study.Methods:HIV-1 infected, ART-naive adults initiating ART in a clinical trial were enrolled. End points included detection of HPV DNA in throat-washes, changes in CD4+ T-cell count and HIV RNA, and oral wart diagnosis.Results:Among 388 participants, 18% had at least one HPV genotype present before initiating ART, and 24% had at least one genotype present after 12–24 weeks of ART. Among those with undetectable oral HPV DNA before ART, median change in CD4+ count from study entry to 4 weeks after ART initiation was larger for those with detectable HPV DNA during follow-up than those without (P = 0.003). Both prevalence and incidence of oral warts were low (3% of participants having oral warts at study entry; 2.5% acquiring oral warts during 48 weeks of follow-up).Conclusion:These results suggest: effective immune control of HPV in the oral cavity of HIV-infected patients is not reconstituted by 24 weeks of ART; whereas ART initiation was not followed by an increase in oral warts, we observed an increase in oral HPV DNA detection after 12–24 weeks. The prevalence of HPV-associated oral malignancies may continue to increase in the modern ART era.