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Try out PMC Labs and tell us what you think. Learn More. Independent risk factors for any oral alpha mucosal HPV among women in the control arm included marital status adjusted odds ratio [AOR], 3. Detection of beta HPV was common Unlike cutaneous HPV types, alpha mucosal HPV types were uncommon in the oral region and were predominately associated with sexual behavior.

Clinical Trials Registration. Studies have reported an increased incidence of oropharyngeal cancer predominantly among younger birth cohorts in developed countries [ 1 — 8 ]. However, little is known about the epidemiology of oral HPV infection.

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Additionally, these studies focused on detection of oral mucosal HPV types from the genus Alphapapillomavirus. Yet, recent evidence suggests that the oral region of healthy individuals also contains a high prevalence of cutaneous HPV types predominantly Betapapillomavirus and Gammapapillomaviruswhich have ly been thought to uniquely infect keratinized epithelium and are associated with skin lesions [ 14 — 18 ].

Few studies have reported the prevalence of oral HPV in resource-poor regions. As such, the aim of the present study was to estimate the prevalence of oral HPV for both mucosal and cutaneous types in a young healthy population of women in Costa Rica, a Latin American country with no reported data on oral HPV prevalence, and to characterize the risk factors for oral HPV in this population. All subjects provided written informed consent.

At annual follow-up visits, clinicians collected cervical cells for cytology and HPV testing from sexually experienced women. Women with low-grade cytologic abnormalities were evaluated semiannually and those with high-grade or persistent low-grade abnormalities were referred for colposcopy and treatment as needed [ 24 ]. At the 4-year annual study visit, a questionnaire regarding the woman's education, marital status, sexual including oral and anal sex and reproductive history, use of contraceptives, and smoking habits was administered.

Associated data

All women were asked to provide an oral sample, and all sexually experienced women were asked to provide cervical and anal specimens. A complete medical history and physical exam were conducted as part of the process of assessment of adverse events.

Information regarding medical conditions, including oral and respiratory conditions, was collected by study clinicians at each follow-up visit. If a condition was reported as present at the time of the study visit, it was confirmed by physical exam. If hospitalization occurred, a doctor reviewed the hospital chart. All medical conditions that affect the oral cavity and upper respiratory tract identified or reported at any point were included in this analysis. The samples were concentrated by centrifugation g for 10 minutes to obtain a pellet that was washed with 10 mL saline solution to remove residual mouthwash, recentrifuged, and then resuspended in 1 mL of saline solution and frozen in liquid nitrogen tanks until testing.

Anal specimens were collected by inserting a dry swab 3—4 cm into the anal canal, rotating once, and then removing the swab while rotation continued using gentle pressure against the wall of the anal canal. The swab was placed in 1 mL of PreservCyt and frozen immediately in liquid nitrogen. Cervical specimens were collected during the pelvic exam see above.

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A convenience sample of women across both arms was tested for cutaneous HPV. Cutaneous HPV types were detected with the skin beta papillomavirus prototype research assay Diassay BV via PCR detection and a reverse-hybridization assay for typing [ 30 ].

Cutaneous HPV types in the alpha, gamma, mu, and nu genera were detected by a broad-spectrum PCR multiplex genotyping assay [ 31 ]. The prevalence of oral HPV was described by the above HPV categorizations among all women and then by arm note that stratification by vaccine arm was only necessary in the evaluation of alpha mucosal HPV types due to vaccine protection [ 28 ]; for other genera, HPV was evaluated across both arms.

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Determinants for oral HPV were evaluated by logistic regression analysis. Variables evaluated in univariate modeling included age, education, marital status, smoking status, age at first vaginal intercourse, lifetime of sexual partners, total of years sexually active, lifetime of oral sex partners, age at first oral sex, lifetime of anal sex partners, and any anal HPV DNA positivity and any cervical HPV DNA positivity each at the contemporaneous study visit as oral specimen collection.

For the oral sex variables, women were asked specifically if they had given oral sex defined as a woman's mouth on her partner's genitals. To evaluate the independent determinants of oral HPV, risk factors that were ificantly associated with oral HPV detection in the univariate analysis or considered important based on the literature ie, smoking, oral sexual behaviorwere included in multivariate models as adjusted odds ratios AORs. Of the women who were randomized, attended the 4-year study visit vaccine and control arm and were invited to provide an oral specimen.

A total of Among the women who provided an oral sample, median age was 26 years, Oral sex was common Participant characteristics of the overall cohort of 5, young adult women from Costa Rica who provided an oral specimen Fuck local women free in Katki HPV DNA testing and the subset of women who were additionally tested for the presence of cutaneous HPV types.

In the control arm, overall prevalence of alpha mucosal HPV types in the oral region was 1. The prevalence of carcinogenic and noncarcinogenic HPV types was 1. The most common noncarcinogenic types were HPV 0. Single oral HPVs were detected in 1. In the vaccine arm, prevalence of HPV and at the 4-year visit was lower than in the control group as ly reported [ 28 ]. Vaccination status did not affect detection of cutaneous HPV types: the overall prevalence of any cutaneous type in the control and vaccine arms were Of all the cutaneous types tested, beta HPV types were the most common.

Overall prevalence of beta HPV was The most common beta types were HPV 3.

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Because of their low individual prevalence, other cutaneous HPV types from the genera alpha, gamma, mu, and nu were grouped; their combined prevalence was 4. Single cutaneous HPVs were detected in ORs were adjusted for categorical age as well as all the variables included in the table. Statistically ificant findings are bolded. In the multivariate analysis, independent risk factors for detection of any oral alpha mucosal HPV included marital status AOR, 3. Finally, the suggestive association of smoking with oral HPV in the univariate analysis lost ificance in the multivariate analysis.

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Stratified analysis confirmed that the effect of smoking was explained by lifetime of sexual partners, as there was little evidence for a smoking effect within strata of lifetime of partners data not shown. Among the women in the control group who reported acute tonsillitis and the 17 women with chronic disease of the tonsils, adenoids, or peritonsillar abscess, none had detectable oral alpha mucosal HPV.

No ificant associations were observed for clinical conditions other than chronic sinusitis.

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A risk factor analysis evaluating exposures that may increase the odds of cutaneous HPV within the oral region was conducted; however, no ificant behavioral risk factors were identified Supplementary Tablesuggesting that detection of these types was not associated with sexual activity. Our analysis, nested within the Costa Rica Vaccine Trial, provides information regarding the epidemiology of oral HPV in a Latin American population of healthy, young adult women.

Both mucosal and cutaneous HPV types were detected within the oral region.

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Independent risk factors for any oral alpha mucosal HPV included marital status, lifetime of sexual partners, chronic sinusitis, and positive cervical HPV status at the 4-year study visit. Unlike the mucosal HPV types, detection of cutaneous HPV types in the oral region appeared independent of sexual activity. It is important to note, however, that detection of HPV using DNA-based methods does not allow us to distinguish active replicative infection which is better assessed by markers of viral activity from detection of virions deposited from recent sexual activity or other HPV-infected areas of one's body.

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The observed prevalence of oral HPV in our population of to year-old women in Costa Rica 0. Likewise, risk factors for oral HPV observed within our population also mirrored those ly reported in US-based studies. As expected, sexual behavior was an important risk factor for oral alpha mucosal HPV, consistent with what is known for HPV epidemiology at other anatomical sites [ 1112 ]. Detection of oral alpha mucosal HPV within our population was independently associated with having a relatively high lifetime of sexual partners.

Being unmarried further increased the risk of oral alpha mucosal HPV after controlling for of sexual partners. Apart from the expected misclassification of sexual behavior reporting, this could suggest the presence of an additional factor not captured by our questionnaire eg, open-mouth kissing [ 11 ].

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Cervical HPV positivity, a marker of sexual behavior, was also a strong risk factor for detection of oral alpha mucosal HPV. Finally, although oral sex and smoking have been consistently reported as risk factors for oral HPV detection [ 1213 ], after adjustment for sexual behavior, the associations observed in our univariate analyses were no longer ificant. Chronic sinusitis was a newly identified risk factor for oral alpha mucosal HPV detection.

Chronic sinusitis is more likely to occur among women with reduced immune responses who in turn may be more susceptible to viral infections [ 32 ]. An alternative explanation may be that sinusitis compromises the integrity of the oral epithelium, a necessary step in cervical HPV infection [ 33 ]. Cutaneous HPV types are highly prevalent in human skin and hair follicles of healthy individuals [ 34 — 38 ].

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Although multiple asymptomatic infections are common, clinical manifestations of cutaneous HPV infection include common, plantar, planar, and genital warts as well as epidermodysplasia verruciformis [ 39 ]. To date, 3 studies reported detection of cutaneous HPV types within the oral region of healthy individuals [ 141718 ]. As in our study, beta HPV types were the predominant cutaneous HPV type detected; however, the prevalence of beta types detected within our population was notably lower Given current knowledge of their biology, these cutaneous HPV types are not believed to be carcinogenic in healthy individuals.

Although the interplay between mucosal and cutaneous HPV is unknown, our superficial analysis suggested they may not be independent. Using data from our large, community-based study in Costa Rica, we extend the reports of low prevalence of oral alpha mucosal HPV in developed countries to a resource-poor country, and confirm its association with sexual behavior.

Future work will evaluate the proportion of the oral HPVs that are detected over time and are therefore more likely to represent true persistent oral infections. Supplementary materials consist of data provided by the author that are published to benefit the reader. The posted materials are not copyedited. The contents of all supplementary data are the sole responsibility of the authors.

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