Nicoletta Termine

HPV in oral squamous cell carcinoma vs head and neck squamous cell carcinoma biopsies: a meta-analysis (1988–2007)

INTRODUCTION In the literature, there exists a wide range of human papillomavirus (HPV) DNA prevalence for head and neck squamous cell carcinoma (HNSCC), especially in relation to methods of viral detection and the lesion site. We estimated the pooled prevalence of HPV DNA in biopsies of HNSCC generically grouped versus oral squamous cell carcinoma (OSCC) in relation to the method of viral DNA detection, with the primary end point of verifying if these two variables (specification of tumour site and method of HPV DNA identification) influence the datum on HPV assay. METHODS By means of MEDLINE/PubMED/Ovid databases, we selected studies examining paraffin-embedded (PE) biopsies of HNSCC and OSCC. According to the inclusion criteria, 62 studies were analyzed. The following data were abstracted: sample size, HPV DNA prevalence, methods of detection [PCR and in situ hybridization (ISH)] and HPV genotypes. After testing the heterogeneity of the studies by the Cochran Q test, metanalysis was performed using the random effects model. RESULTS The pooled prevalence of HPV DNA in the overall samples (Sigma: 4852) was 34.5%, in OSCC it was 38.1% and in the not site-specific HNSCC was 24.1%. With regard to the detection method, PCR-based studies reported a higher prevalence rate than ISH-based rates (34.8, versus 32.9%) especially in the OSCC subgroup (OSCC PCR based: 39.9%). CONCLUSION These findings support the assumption that a correct distinction of HNSCC by site, together with the use of more sensitive HPV DNA detection methods, should be considered as essential prerogatives in designing future investigations into viral prevalence in head and neck tumors.

Oral human papillomavirus infection in women with cervical HPV infection: New data from an Italian cohort and a metanalysis of the literature

A key issue in oral HPV infection is whether it can be associated with a genital HPV infection, or whether it can be considered as an independent event. This analysis evaluated the frequency and type-concordance of oral HPV infection in women with cervical HPV infection by means of: (i) a cross-sectional study on a sample (n=98) of Italian women; and (ii) a literature-based metanalysis, including the experimental study the subject of this Paper and nine other published studies (n=1017), which also examined the influence of oral sampling procedure (oral brushing vs oral rinse) and HIV status on oral HPV detection. The prevalence of oral HPV infection in the Italian study was 14.3% (95% CI: 7.4-21.2); the prevalence of type-concordance was 21.4% (95% CI: 0.0-43.6) and it was only marginally significant (P=0.05). The prevalence of oral HPV infection in the metanalysis was estimated as 18.1% (95% CI: 10.3-25.9); the prevalence of type-concordance was 27.0% (95% CI: 12.3-41.7), and it was statistically significant (P=0.002). The metanalysis also showed that the oral sampling procedure was not a determinant of HPV detection; however, HIV status increased the likelihood of oral HPV infection (HIV-positive vs negative: 27.2%; 95% CI: 22.1-32.2 vs 15.5%; 95% CI: 6.9-24.2) and type-concordance (HIV-positive vs negative: 46.8%; 95% CI: 34.7-58.9 vs 15.6%; 95% CI: 0.8-30.4). Oral HPV infection and type-concordance in women with cervical HPV infection are more prevalent than could be expected by chance; this finding is consistent with the notion of a degree of dependence of the oral site on the cervical site. Furthermore, oral HPV prevalence and type-concordance are influenced by immunity.

Low rate of oral human papillomavirus (HPV) infection in women screened for cervical HPV infection in Southern Italy: A cross‐sectional study of 140 immunocompetent subjects

Even though the natural history of cervical and oral human papillomavirus (HPV) infection has been investigated intensely, the possibility that HPV may infect both sites in the same subject is not well documented. This study investigated the frequency of concurrent oral and cervical HPV infection in southern Italian women, in the light of some selected socio‐behavioral variables. One hundred forty women (mean age: 36 years), with known cervical HPV status, were analyzed for oral HPV. Age, smoking/drinking habits, clinical and socio‐behavioral history were assessed by personal interviews. Oral mucosal cells were collected by oral brushing and HPV DNA was sought by the use of nested PCR amplification followed by direct DNA sequencing and the commercial assay INNOLiPA HPV Genotyping (Innogenetics N.V., Ghent, Belgium). The data were analyzed by using the chi‐square test and a logistic regression (logit) model (P < 0.05 statistically significant). Oral HPV infection was detected in 2/140 (1.4%) cases, being present in 2/76 (2.6%) women with cervical HPV infection and 0/64 uninfected women (P = 0.19). A lack of type‐specific concordance in the two patients with concurrent infection was observed. In the sample of population examined, HPV cervical infection does not seem to predispose to oral transmission, even in the presence of oral–genital sexual habits, thus suggesting the independence of infection at the two mucosal sites. J. Med. Virol. 81:1438–1443, 2009.

Mucoadhesive Polymers for Oral Transmucosal Drug Delivery: A Review

The oral mucosa offers an interesting site for the application of dosage forms that release drugs within/throughout the oral mucosa, by assuring a high drug bioavailability for topic and systemic effects. However, the relative permeability of the oral mucosa and the washing effect related to the oral fluids and mechanical stresses must be considered in the formulation of oral dosage forms. Since a sustained drug release can be guaranteed only if dosage forms remain in contact with the oral site of absorption/application for a prolonged time, the development of mucoadhesive dosage forms is mandatory. The mucoadhesion is a complex phenomenon and the mucoadhesive bond consists of two different parts, the mucoadhesive polymers and the mucous substrate. In addition to factors related to the oral mucosa and oral environment features, the physical-chemical characteristics of mucoadhesive polymers must be also considered as factors influencing the mucoadhesive bonds. While it is not possible to modify the mucosal features or it is possible to modify or inhibit only in part certain mucosal processes, the knowledge of polymer properties influencing mucoadhesive bonds allows to modify or to control these properties in developing increasingly effective mucoadhesive systems. The aims of this review are to discuss the several mechanisms and factors behind the phenomenon of mucoadhesion with particular reference to the features of the oral environment, oral mucosa, and polymeric compounds influencing mucoadhesion process. Finally, a brief mention to the main mucoadhesive dosage forms designed for oral transmucosal drug delivery is made.

Biopsy vs. brushing: Comparison of two sampling methods for the detection of HPV-DNA in squamous cell carcinoma of the oral cavity

BACKGROUND HR HPV infection was proposed as aetiological factor of oral squamous cell carcinomas (OSCC). HPV frequency in OSCC is highly variable, due to the discrepancy in oral sampling procedures, HPV testing methods and inclusion criteria regarding tumour site (strictly oral cavity vs. nearby structures). Our aim was to compare HPV DNA frequency and type-specific distribution in paired cytological and histological samples of SCC strictly located in oral cavity. The correlation between HPV detection rate by each method of sampling and demographical, behavioural and clinical-pathological variables was also examined. PATIENTS AND METHODS HPV DNA was detected in brushed cells and formalin-fixed paraffin-embedded biopsies obtained from 83 consecutive unselected immunocompetent adults with OSCC. HPV DNA detection was performed in all samples by nPCR followed by direct DNA sequencing and the assay INNO-LiPA HPV Genotyping. Univariate and multivariate statistics were used, including Cohen κ index to evaluate agreement between two methods and association between HPV infection and demographical, behavioural and clinical-pathological variables for each method of sampling (p<0.05 statistically significant). RESULTS HPV DNA was detected in 15.7% (13/83) of brushings and 12.1% (10/83) of biopsies (p>0.05). High risk HPV 51, 16 and 39 were genotypes more frequently detected, especially among biopsies; no concordance between two methods was found (Cohen κ index=0.04, p=0.34). CONCLUSION A fraction of OSCC could be linked to HR HPV infection in the Mediterranean area. Although without a statistical significance, biopsy specimen demonstrated more accurate for HR HPV detection than brushing in OSCC.

Oral HPV Infection: Current Strategies for Prevention and Therapy

Infection with High Risk (HR) Human Papillomaviruses (HPVs) is the main aetiological agent of Cervical Squamous Cell Carcinoma (CSCC) and also associated in a subgroup of other neoplasms, including Oropharyngeal Squamous cell Carcinoma (OPSCC). HPV infection, in genital as in oral mucosa, can also be subclinical or associated with benign proliferative lesions (common warts, condylomas, papillomas) caused mostly by infection with Low Risk (LR)-HPVs. In the last decades, extensive research has resulted in growing knowledge on HPV biology and specifically viral life cycle, biochemical properties of viral proteins and their interaction with the host proteins leading to potential new targets of prophylactic or therapeutic vaccines and therapies for HPV infection. In addition, notable progresses have been made in the field of diagnostics to detect HPV DNA or RNA. The recent epidemiological data suggest the significant changes in HPV endemic, due to the changes in sexual habits especially among young generations (i.e. early sexual debuts, multiple sexual partners, oral and anal sex); this scenario has urged on the need of adequate campaigns of primary (sexual education, vaccination programs) and secondary prevention (diagnostics of HPV-related diseases). Due to the growing interest on HPV infection and HPV related cancers, the authors made a narrative review of the literature on oral HPV infection and oral-genital transmission. After this, in view of the controversies about the strategies of therapy and prevention of HPV infection, the present review focuses on the current state of art about the available tools for the therapeutic and, if any, preventive management of oral HPV infection.

Long-standing oral ulcers: proposal for a new `S-C-D classification system’: Chronic oral ulcers

Persistent oral ulcers and erosions can be the final common manifestation, sometimes clinically indistinguishable, of a diverse spectrum of conditions ranging from traumatic lesions, infectious diseases, systemic and local immune-mediated lesions up to neoplasms. The process of making correct diagnosis for persistent oral ulcers still represents a challenge to clinicians. Major diagnostic criteria should include the clinical appearance of both ulcer and surrounding non-ulcerated mucosa, together with the evaluation of associated signs and symptoms, such as: number (single or multiple), shape, severity of the ulcer(s), conditions of remaining mucosa (white, red or with vesiculo-bullous lesions) and systemic involvement (e.g. fever, lymphadenopathy or evaluation of haematological changes). The aim of this paper was to review the literature relating to persistent oral ulcers and provide a helpful, clinical-based diagnostic tool for recognising long-standing ulcers in clinical dental practice. The authors, therefore, suggest distinguishing simple, complex and destroying (S-C-D system) ulcerations, as each requires different diagnostic evaluations and management. This classification has arisen from studying the current English literature relating to this topic, performed using MEDLINE / PubMed / Ovid databases.