Human Papilloma Virus associated with oral cancer and preventive strategies: the role of vaccines.

The aim of this paper is to describe the efficacy of Human Papilloma Virus (HPV) vaccines for preventing oral cancer. A systematic review of the literature was conducted to describe the state of the art about HPV vaccines for preventing oral cancer. The aspects of prevention and control of infection by administering vaccines and the diffusion of sexual education campaigns are discussed also. In recent years there has been a growing interest in HPV in dentistry, suggesting a role of such a family of viruses in the development of oral cancers as well as of the uterine cervix. Even if the mass media have increasingly faced the problem, causing frequent alarming among patients, the dentist therefore needs a complete and up-to-date knowledge of this infectious condition that is one of the most common causes of sexually transmitted mucous membrane infections (eg genital, anal and oral). Recent studies about HPV infection are a basic requirement in order to promote the HPV vaccinations and patient’s health.

HPV acting on E-cadherin, p53 and p16: literature review.

In addition to tobacco and alcohol consumption, the two main risk factors for oral squamous cell carcinoma (OSCC), recent studies have revealed infections with human papilloma virus (HPV) as an additional risk factor for OSCC development. In the field of head and neck malignancies, the prevalence of HPV infections in oropharyngeal cancer (OC) ranges in different studies up to 84%. While HPV infection is discussed as an independent risk factor in this region, its distinguished role in carcinogenesis of tumours localized to the oral cavity remains uncertain. A systematic literature search was performed using PubMed, Cochrane library, Science Direct, and the Internet search, with language restricted to English. The search included published studies which dealt with detection methods of HPV-related oral and oropharyngeal cancers and biomolecular studies, particularly regarding the compromising of p53 p16 and e-cadherin’s. P53 Tumour suppressor protein p53 has several functions that are related to maintaining genomic stability and inhibiting cell proliferation in response to DNA damage. For preventing neoplasia to occur, the most important of these functions are cessation of cell growth and induction of either apoptosis or senescence. P16 is a cellular protein involved in cell cycle regulation. It is a cyclin-dependent kinase 4 (CDK4) inhibitor, and is integral to Rb mediated regulation of G1-S phase of the cell cycle. P16 is expressed at a very low level in normal cell as Rb inhibits transcription of p16. Various detection methods ranging from immunohistochemistry (IHC) to molecular techniques have been used to determine the HPV status of HNSCC. E-cadherin, a 120 kDa Type I classical cadherin, is expressed primarily on epithelial cells. It is found on the surface of keratinocytesand Langerhans cells (LC) and E-cadherin mediated adhesion between these cell types is required for LC retention in the epidermis. It is also an important tumour suppressor protein: its loss or inactivation is associated with epithelial-to-mesenchymal transition (EMT), a process involving dedifferentiation, infiltration and metastasis of tumours. Oral carcinogenesis is a multi-factorial process involving socioeconomic, environmental and microbial factors leading to multistep changes. Smoking and tobacco exposure seems to modify the survival and recurrence of HPV positive tumours and should be considered in future trials for risk stratification of HPV positive patients. HPV associated oropharynx cancer represents a distinct clinical and biologic entity with many unresolved issues that will be investigated in future translational, clinical research. We need to further explore and understand why the disease occurs predominantly in males, and whether the natural history of oral HPV infection differences in men and women.

Human papilloma virus in the tonsillar microbiota of an Afghan population group.

Cancer of the oral cavity is known to have a diverse aetiology that includes infectious agents. Human papilloma virus has been found to be associated with several types of human cancer, inclusive of cervical, vulvar, vaginal, penile, anal, and cancer of tonsil. The aim of this manuscript is to investigate the presence of human papilloma virus in tonsillar microbiota of an Afghan population group. A sample of the tonsillar microbiota was collected by oral swab paper stick from 80 healthy donors. The sample was investigated for the presence of high-risk human papillomavirus types 16, 18, 31 and 45 by real time PCR. Eight samples produced some positive endpoint signals for human papillomaviruses. The human papillomavirus 31 was the unique papillomavirus detected; its calculated prevalence rate was 0.10 (C.I. 0.05-0.19). However, the viral load was always very low, in the order of 10-3 viral genomes per cell. The high prevalence of high-risk human papillomavirus in healthy population suggest a need for further investigation on virus spreading and supports the development of vaccination strategies.

HPV infection in the oral cavity: epidemiology, clinical manifestations and relationship with oral cancer.

PURPOSE: The aim of this paper is to describe epidemiology and clinical manifestations of oral infection by Human papillomavirus (HPV), with particular attention to potential malignant lesions. MATERIALS AND METHODS: A systematic review of the literature was conducted to describe the state of the art about HPV infection in oropharyngeal mucosa and its modalities of transmission, with particular attention to possible simultaneous infection in multiple anatomic sites. The aspects of prevention and control of infection by administering vaccines and the diffusion of sexual education campaigns are discussed also. Therapeutic protocols are also described where necessary. RESULTS: In recent years there has been a growing interest in HPV oral medicine, suggesting a role of such a family of viruses in the development of neoplasms of the oropharyngeal district as well as of the uterine cervix. Even if the mass media have increasingly faced the problem, causing frequent alarming among patients, the dentist therefore needs a complete and up-to-date knowledge of this infectious condition that is one of the most common causes of sexually transmitted mucous membrane infections (e.g. genital, anal and oral). CONCLUSIONS: Recent studies about HPV infection are a basic requirement in order to promote the health of patients and provide them with the most exhaustive indications from dentists.

Genetic susceptibility and periodontal disease: a retrospective study on a large italian sample.

BACKGROUND: Periodontal disease (PD) is a multifactorial illness in which environment and host interact. The genetic component plays a key role in the onset of PD. In fact the genetic compound can modulate the inflammation of the mucous membranes and the loss of alveolar bone. The genetics of PD is not well understood. Previous studies suggest a strong association between PD occurrence and individual genetic profile. The role of genetic susceptibility could impact on the clinical manifestations of PD, and consequently on prevention and therapy. MATERIALS AND METHODS: Genetic polymorphisms of VRD, IL6 and IL10 were investigated in Italian adults affected by PD. 571 cases classified according the criteria of the American Academy of Periodontology were included. All patients were Italian coming from three areas according to italian institute of statistics (ISTAT) (www.istat.it/it/archivio/regioni). The sample comprised 379 patients from North (66%), 152 from Central (26%) and 40 of South (8%). RESULTS: No significant differences were found among allele distribution. CONCLUSION: Chronic PD is a complex disease caused by a combination of genetic susceptibility, patients habits (oral hygiene, smoking, alcohol consumption) and oral pathogens. In our report no differences were detected among three Italian regions in allele distribution.

An unusual, deceptive delayed of profuse haemorrhage after mandibular implant dentistry: risk planning and medico-legal instruction.

Mandibular implant placement (MIP) has been accepted and widely used for decades all over the world, and has reached a very high level of therapeutic reliability. MIP is used mostly in elderly edentulous patients who lost their teeth when dentistry was not oriented to fixed or removable prosthetic. Notwithstanding this, every year cases of severe complications during MIP due to haemorrhage causing life-threatening airway's obstruction are reported. These severe complications of MIP need immediate therapy, usually with hospitalization, and may be potentially fatal. A 56-year-old man presented to the private practice requesting the placement of two dental implants at 41 and 31 previously lost for periodontal disease. Two implants of 3.3 mm of diameter, and 10 mm of length were inserted replacing teeth 31 and 41. Two hours after surgery and home delivery, the patient came to the emergency room complaining of dyspnoea and edema at the floor of the mouth. The maxillo-facial surgeon decided to perform tracheostomy and haemostasis under general anaesthesia. Two weeks after demission a complete healing was performed. This is important for dental practitioners to avoid severe bleeding complications during the MIP in the interforaminal region, especially on the midline. Moreover, when mandibles are severely atrophic, practitioners should be aware of this fact and the possible implications. The evaluation of these data is essential in the correct preoperative planning of implant procedures in the mandible, and with the increasing demand for MIP, the variations of the lingual foramen of the mandible should receive more attention.

Clinical outcome of a two-piece implant system with an internal hexagonal connection: a prospective study.

The purpose of this prospective clinical study was to evaluate the survival rate (SVR - i.e. fixtures still in place at the end of the observation period) and success rate (SCR - i.e. bone resorption around implant neck) of an implant system characterized by cylindrical and tapered implants, both provided with an internal hexagonal connection. In the period between January 1996 and October 2011, 52 implants with internal hexagonal connection were inserted in 21 females and 31 males, mean age 54±11 years. The mean post-surgical follow-up was 44.6±34.4 months. Several parameters were evaluated as potential outcome conditioners: age, gender, smoking, replaced tooth, periodontal disease, fixture shape (i.e. cylindrical or tapered), jaw location (i.e. maxilla or mandible), bone graft, immediate loading, post-extractive placement, type of prosthesis (i.e. single crown or bridge), edentulism, implant diameter and length. An SPSS statistical program was used and Cox regression analysis performed. SVR was 100% since no fixtures were lost. SCR, expressed through the mean marginal bone loss, was 77%. No significant differences were found, for most of the parameters analyzed, with the exception of prosthetic bridges, where implants supporting this type of rehabilitation showed a worse clinical outcome in comparison to single crown rehabilitations. Internal hexagonal connection is a reliable tool for oral rehabilitation.

Maxillary sinus by-pass with tilted implants via tapered-screw bone expanders in low density bone: one year follow -up of a case series.

In the present paper the use of tapered-screw bone expanders (TSBEs) is proposed, in combination with the placement of tilted implants in close proximity to the anterior sinus wall, solving the problem of the reduced height of the alveolar bone in the sub-antral area. The Authors named the procedure: Tilted Implant Expansion Osteotomy (TIEO). Fifteen patients (10 females and 5 males, mean age 47.8±8.15 years) with distal edentulous maxillae were enrolled in this study. For each edentulous site 2 implants were placed, the anterior implant in the area of the most anterior missing tooth while, the posterior implant, immediately in front of the maxillary sinus, with an inclined position. Adopting the aforesaid procedure, 34 cylindrical two-piece implants were placed, 17 of which were placed in tilted position, in order to by-pass the maxillary sinus. After a healing period of 4-6 months, the second stage surgery was performed. The cases were finalized by metal-ceramic cementable restorations with a variable number of elements, from 2 to 4, without any cantilever element. The post finalization follow-up was at 12 months. Survival rate was 100% since no fixtures were lost. At the one-year follow-up the clinical and radiological appearance of the soft and hard tissues was optimal and no pathological signs were recorded. TIEO is a promising surgical procedure for oral rehabilitation of maxillary edentulous sites and represents a therapeutic alternative to sinus lift techniques.

Modified connective tissue punch technique to increase the vestibular/buccal keratinized tissue on flapless implant surgery: a case series.

The aim of this article is to show a simple and predictable technique to enhance both the vestibular/buccal (V/B) gingival thickness (GT) and keratinized tissue width (KTW) improving the soft-tissue profile after flapless implant placement. The technique proposed was named Modified Connective Tissue Punch (MCTP). Fourteen patients (6 men and 8 women) aged between 35 and 69 years (mean value 48.07±13.023 years) were enrolled in this case series. Seventeen implant sites were submitted to flapless procedure. The connective punch (CP) was harvested with a motor-driven circular tissue punch and then a full-split dissection was executed, in order to create a deep pouch, beyond the mucogingival junction, on the V/B side. In this recipient site the CP was placed. The normal flapless surgical protocol was used; implants were inserted and covered with transgingival healing cap screws. GT and KTW were measured: both immediately before and after surgery; at the time of the prosthetic finalization (3-4months, respectively, for mandible and maxilla); 1 year post surgery follow-up. GT was measured at 1 mm, 2 mm and 5 mm on the V/B side, from the outline of the punch. Both KTW and GT at 1 and 2 mm can be effectively increased, while no significant effects for GT at 5 mm can be expected from this technique. Furthermore, the mean values of KTW and GT at 1 mm and 2 mm show significant increases at 3-4 months post-operative, while no further significant increments are shown at 1 year post-operative follow-up. The Authors recommend the use of the MCTP technique to reduce the number of aesthetic complications and soft tissue defects in flapless implant surgery. Longer follow-ups are needed to evaluate the stability of peri-implant tissues over time.

Retrospective study on bone-level and soft-tissue-level cylindrical implants.

The purpose of this prospective clinical study was to evaluate the survival rate (SVR - i.e. fixtures still in place at the end of the observation period) and success rate (SCR - i.e. bone resorption around implant neck) of two cylindrical implant systems. Both systems were equipped with a tapered connection, one requiring a bone-level (BL) placement, while the other a soft-tissue-level (STL) placement. In the period between January 1996 and October 2011, a total of 150 implants (76 in females and 74 in males, mean age 60±11 years) were inserted. The mean post-surgical follow-up was 84±47 months. Several parameters were evaluated as potential outcome conditioners: age, gender, diabetes, smoking, periodontitis, type of edentulism, replaced tooth, jaw location (i.e. maxilla or mandible), bone graft, immediate loading, post-extractive, type of prosthesis, implant diameter and length. An SPSS program was used for statistical analysis. Only two fixtures were lost, therefore SVR was 98.7%. SCR, expressed through the mean marginal bone loss, was 92%. The mean peri-implant bone loss was 0.121.47 mm for BL implants and 0.041.3 mm for STL implants. None of the studied variables had a statistical significant impact on SVR or SCR. Cylindrical implants are reliable for oral rehabilitation.

The influence of “conical plus octagonal” internal connection on implant survival and success rate: a retrospective study of 66 fixtures.

Implant oral rehabilitation has become one of the most successful dentistry techniques over the last 30 years. However, peri-implantitis is the most important complication in implant dentistry. Peri-implantits can be caused by inadequate implant-abutment connections (IAC). The aim of our study is to evaluate the influence of “conical plus octagonal” (i.e. I-Fix connection) on implant survival and success rate. All the implants included in this study were of a completely new type (I-Fix implants and abutments by FMD Falappa Medical Devices S.p.A. Rome, Italy). Sixty-six implants were inserted in males and females. The implants were of different diameters and lengths, inserted both in the mandible and in the maxilla with immediate or delayed loading, with guided bone regeneration (GBR), and post-extractive surgery. All implants were provided with I-Fix connection, 64 abutments using passing screws and 2 using full screws. None of the 66 implants were lost (i.e. survival rate - SVR = 100%). Cox-regression analysis demonstrated that diabetes (p=0.0074), GBR (p=0.0115), maxilla (p=0.0117) and smoking (p=0.0194) have a statistical significant impact on clinical outcome (i.e. greater bone resorption around implant neck). Our data show that I-Fix connection did not influence SVR. This finding demonstrates that I-Fix design seemed to significantly affect the survival rate of the implants in a recent meta-analysis. In spite of the limits of our study, I-Fix connection has been demonstrated to be efficient in closing the gap between implant and abutment and maintaining a good connection over time.

Why should patients with systemic disease and tobacco smokers go to the dentist?

Periodontal diseases (PD) affect about half of the adult population all over the world. PD is caused by bacterial infection which induces an inflammatory response with progressive destruction of the periodontal tissues and finally the loss of teeth. Tobacco smoking (TS), alcohol consumption, and systemic diseases (SDs), such as cardiovascular diseases, diabetes mellitus, respiratory diseases, osteoporosis, malnutrition and stress, are considered additional risk factors. This short review examines the potential causal association between PD, TS and SDs. There is strong evidence that PD is associated with an increased risk of SDs. In addition, many patients with SDs are also affected by PD, which can be mild or severe, and tobacco smokers manifest a greater risk of developing PD. The aim of this manuscript is to investigate the effects of periodontal therapy on the management of SDs and influence of TS on PD. This manuscript includes many randomized controlled trials and reviews to test the effects of different periodontal therapies for patients with SDs. A definite conclusion on the relationship between PD and SDs is lacking, however, there is sufficient evidence to justify periodontal treatment to prevent SDs; in fact, PD is prevalent in the middle-aged population and can have a significant impact on systemic health.

PERIODONTAL POCKETS AS A RESERVOIR OF HELICOBACTER PYLORI CAUSING RELAPSE OF GASTRIC ULCER: A REVIEW OF THE LITERATURE.

Helicobacter pylori (HP) is one of the most common gastric infections in the world, affecting about half the world’s population and is the principal cause of adenocarcinoma of the distal stomach. It seems that HP infects the subject early in life and is transmitted from person to person. The HP reaches the stomach through oral ingestion, and because of its non-invasive nature, the stomach is the ultimate site of colonization. Recently, it has been debated whether the oral cavity is a reservoir of HP bacteria participating in infection transmission, or representing a nidus of re-infection after eradication of the bacterium. HP and recurrent aphthous stomatitis (RAS) show similar clinical and histological findings, and the discovery of HP in RAS ulcers support the idea of a correlation between the two diseases. Another important relationship between RAS and HP is the high incidence of anemia in patients with RAS that may be caused by HP-positive stomach disease. In fact, antibiotic therapy and treatment of anemia can reduce the frequency of RAS ulcer recurrence. HP is considered a carcinogenic agent type 1 of the stomach by the International Agency for Research on Cancer. In conclusion, the oral cavity is an extra-gastric reservoir of HP and periodontal therapy associated with systemic therapy can better eradicate HP from the mucosa of all gastro-enteric tract, reducing relapse of HP infection. Prospective cohort studies are needed to demonstrate the bacterial action in the oral cavity.

Pathology of choroid plexus papillomas: a review.

Choroid plexus papillomas (CPPs) are rare, usually slow growing neoplasms. Their biological behaviour cannot be predicted in an individual case. Furthermore, the neuropathological diagnosis of these neoplasms is occasionally difficult because light and electron microscopical and immunohistochemical features may overlap with those of other neoplasms localising in the choroid plexus. The aim of this paper is to review the pathological literature (light and electron microscopy (EM) and immunocytochemistry), to provide guidance on current diagnostic tools and criteria and address the identification of 'atypical' CPPs, e.g. those CPPs with histological features indicative of aggressive behaviour, in an attempt to help bridge the diagnostic gap between benign CPPs on the one hand and choroid plexus carcinomas (CPCs) on the other.

The "VGF" protein in rat adenohypophysis: sex differences and changes during the estrous cycle and after gonadectomy.

Gene expression and cell localization of the neuroendocrine protein VGF were studied in the rat anterior pituitary. In females, four antisera against nonoverlapping regions of VGF immunostained a small number of lactotropes and many gonadotropes. In the latter cells, VGF immunoreactivity was localized to a subpopulation of secretory granules. Distinct changes were seen after estrus, with a significant increase in VGF messenger RNA (whole pituitary), whereas VGF immunostaining was strikingly reduced in gonadotropes and somewhat more abundant in lactotropes. In male rats, gene expression was low, and immunoreactivity was restricted to a few lactotropes. After castration or ovariectomy, VGF messenger RNA was high, and VGF immunoreactivity was abundant in gonadotropes. Selective localization and cyclic modulation suggest involvement of the VGF gene product(s) in pituitary gonadotrope and/or lactotrope function.

Numerical chromosome changes in a nasal polyp.

The etiology of nasal polyposis is not fully understood. We found numerical chromosome changes in one out of five cytogenetically investigated nasal polyps. The histological picture of this case was characterized by the presence of histiocyte-like cells, which were absent in the remaining cytogenetically normal polyps.