Abstract

BackgroundWe have previously shown the high prevalence of oral anti-human papillomavirus type 16 (HPV-16) antibodies in women with HPV-associated cervical neoplasia. It was postulated that the HPV antibodies were initiated after HPV antigenic stimulation at the cervix via the common mucosal immune system. The present study aimed to further evaluate the effectiveness of oral fluid testing for detecting the mucosal humoral response to HPV infection and to advance our limited understanding of the immune response to HPV.MethodsThe prevalence of oral HPV infection and oral antibodies to HPV types 16, 18 and 11 was determined in a normal, healthy population of children, adolescents and adults, both male and female, attending a dental clinic. HPV types in buccal cells were determined by DNA sequencing. Oral fluid was collected from the gingival crevice of the mouth by the OraSure method. HPV-16, HPV-18 and HPV-11 antibodies in oral fluid were detected by virus-like particle-based enzyme-linked immunosorbent assay. As a reference group 44 women with cervical neoplasia were included in the study.ResultsOral HPV infection was highest in children (9/114, 7.9%), followed by adolescents (4/78, 5.1%), and lowest in normal adults (4/116, 3.5%). The predominant HPV type found was HPV-13 (7/22, 31.8%) followed by HPV-32 (5/22, 22.7%). The prevalence of oral antibodies to HPV-16, HPV-18 and HPV-11 was low in children and increased substantially in adolescents and normal adults. Oral HPV-16 IgA was significantly more prevalent in women with cervical neoplasia (30/44, 68.2%) than the women from the dental clinic (18/69, 26.1% P = 0.0001). Significantly more adult men than women displayed oral HPV-16 IgA (30/47 compared with 18/69, OR 5.0, 95% CI 2.09–12.1, P < 0.001) and HPV-18 IgA (17/47 compared with 13/69, OR 2.4, 95% CI 0.97–6.2, P = 0.04).ConclusionThe increased prevalence of oral HPV antibodies in adolescent individuals compared with children was attributed to the onset of sexual activity. The increased prevalence of oral anti-HPV IgA in men compared with women was noteworthy considering reportedly fewer men than women make serum antibodies, and warrants further investigation.

Highlights

  • We have previously shown the high prevalence of oral anti-human papillomavirus type 16 (HPV-16) antibodies in women with human papillomaviruses (HPV)-associated cervical neoplasia

  • We previously described the presence of oral fluid HPV-16 IgA and IgG antibodies in the majority of women with cervical neoplasia [10]

  • In a small pilot study we found that oral HPV-16 IgA, when compared with serum and cervico-vaginal rinse antibodies, most closely correlated with HPV-16 DNA at the cervical lesion of women with cervical intraepithelial neoplasia (CIN) [7] This indicated that oral IgA could be a useful biomarker of mucosal HPV infection at a genital site via the common mucosal immune system [11]

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Summary

Introduction

We have previously shown the high prevalence of oral anti-human papillomavirus type 16 (HPV-16) antibodies in women with HPV-associated cervical neoplasia. The present study aimed to further evaluate the effectiveness of oral fluid testing for detecting the mucosal humoral response to HPV infection and to advance our limited understanding of the immune response to HPV. Oral HPV infection shows the typical fluctuating presence observed in anogenital mucosa [6]. The introduction of appropriate vaccines to an area will require knowledge of the HPV types within the general population and those associated with cervical [8] and other cancers. Vaccine introduction will require monitoring of the immune response in vaccinees during clinical trials and within a public health vaccine program the testing of children and young people for exposure to HPV prior to vaccination. There is the need for easy, safe, non-invasive sampling methods for the determination of HPV infection and of the immune responses to HPV

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