In contrast to cervical cancer, integration of human papillomavirus (HPV) DNA into the host genome has been considered a rare event in cancer precursor lesions (cervical intraepithelial neoplasia [CIN]). With our new real-time PCR method, we demonstrated that integrated HPV type 16 (HPV16) is already present in CIN lesions. The physical state of HPV16 and the viral load were simultaneously detected. A unique region of the E2 open reading frame (ORF) that is most often deleted during HPV16 integration is targeted by one set of PCR primers and a probe, and another set targets the E6 ORF. In episomal form, both targets should be equivalent, while in integrated form, the copy numbers of E2 would be less than those of E6. The method was tested with DNAs from 31 cervical lesions (non-CIN to CINIII) from 24 women prospectively followed up for 10 years. This report presents viral load and integration results from the largest series of CIN lesions described to date. Only one sample contained exclusively episomal HPV16 DNA, and this lesion regressed spontaneously. Samples from another patient, with only integrated HPV16, rapidly progressed from CINI to CINIII in 2 years. In all other patients, episomal and integrated forms of HPV16 DNA were found to coexist. Rapid progression of the CIN lesions was closely associated with a heavy load of integrated HPV16. Thus, the method described here is a very sensitive tool with which to assess the physical state of HPV, which is useful in predicting disease progression.

Oral Diseases(2011)17(Suppl. 1), 58–72Objectives: Human papillomavirus (HPV) in oral carcinoma (OSCC) and potentially malignant disorders (OPMD) is controversial. The primary aim was to calculate pooled risk estimates for the association of HPV with OSCC and OPMD when compared with healthy oral mucosa as controls. We also examined the effects of sampling techniques on HPV detection rates.Methods: Systematic review was performed using PubMed (January 1966–September 2010) and EMBASE (January 1990–September 2010). Eligible studies included randomized controlled, cohort and cross‐sectional studies. Pooled data were analysed by calculating odds ratios, using a random effects model. Risk of bias was based on characteristics of study group, appropriateness of the control group and prospective design.Results: Of the 1121 publications identified, 39 cross‐sectional studies met the inclusion criteria. Collectively, 1885 cases and 2248 controls of OSCC and 956 cases and 675 controls of OPMD were available for analysis. Significant association was found between pooled HPV‐DNA detection and OSCC (OR = 3.98; 95% CI: 2.62–6.02) and even for HPV16 only (OR = 3.86; 95% CI: 2.16–6.86). HPV was also associated with OPMD (OR = 3.87; 95% CI: 2.87–5.21). In a subgroup analysis of OPMD, HPV was also associated with oral leukoplakia (OR = 4.03; 95% CI: 2.34–6.92), oral lichen planus (OR = 5.12; 95% CI: 2.40–10.93), and epithelial dysplasia (OR = 5.10; 95% CI: 2.03–12.80).Conclusions: The results suggest a potentially important causal association between HPV and OSCC and OPMD.

Since human papillomavirus (HPV) was first linked to laryngeal/oral carcinomas in 1983, several studies have confirmed its causal role in a subgroup of upper aerodigestive tract tumours. Of the non-genital cancers, tonsillar carcinomas (TCs) have the strongest association with HPV. By the end of 2002, 432 TCs had been analysed for HPV DNA. Overall detection rate was 51%, with HPV-16 being the most prevalent (84%). The original proposal that HPV-33 would be the most frequent HPV in TCs has not been confirmed, being present in only 4.6% of cases. HPV copy numbers are similar to those found in genital carcinomas (10–300 copies/cell), although HPV is mainly episomal in TC. The importance of this observation is unclear, although a role for subepithelial proliferative lymphatic tissue has been speculated. Patients with HPV-16 positive tumours have better overall and disease specific survival than HPV negative patients. They are also younger and the association with conventional risk factors—smoking and drinking—is less significant than in HPV negative patients. Thus, recent data suggest a distinct pattern for HPV-16 positive TCs.

To date, more than 100 types of human papillomavirus (HPV) have been identified. In the past 20 years, there has been an increasing interest in HPVs because of their potential role in the pathogenesis of malignant tumors. HPV infections are known to affect predominantly adult, sexually active age groups, whereas skin warts, at various anatomic sites, are usually associated with younger individuals. The modes of viral transmission in children remain controversial, including perinatal transmission, auto- and hetero-inoculation, sexual abuse, and, possibly, indirect transmission via fomites. Recent studies on perinatal infection with HPV have been inconclusive. It is still unclear how frequently perinatal infection progresses to clinical lesions, whether genital, laryngeal, or oral. Conflicting reports have been published on the prevalence of HPV infections in children. The current consensus is, however, that newborn babies can be exposed to cervical HPV infection of the mother. The detection rate of HPV DNA in oral swabs of newborn babies varies from 4% to 87%. The concordance of HPV types detected in newborn babies and their mothers is in the range of 57% to 69%, indicating that the infants might acquire the HPV infection post-natally from a variety of sources. HPV antibodies have been detected in 10% to 57% of the children, and there is usually no correlation between seropositivity and the detection of HPV DNA in either the oral or the genital mucosa. There is also evidence that transmission in utero or post-natal acquisition is possible. The mode of in utero transmission remains unknown, but theoretically the virus could be acquired hematogenously, by semen at fertilization, or as an ascending infection in the mother. The understanding of viral transmission routes is important, particularly because several vaccination programs are being planned worldwide. The serologic response to HPV detected in different populations of young women or women at risk of cervical cancer might be due to genital infections, but the possibility that HPV infection has been acquired earlier in life through the oral mucosa or respiratory tract cannot be ruled out.