Both mucosal and cutaneous papillomaviruses are in the oral cavity but only alpha genus seems to be associated with cancer.

BACKGROUND: Human papillomaviruses are associated with invasive cancers in the cervical, anogenital, and oropharyngeal areas. Persistent HPV infections, particularly with high-risk HPV such as HPV 16, are involved in the carcinogenesis of a subset of oropharyngeal cancers. The majority of published studies on HPV prevalence in these tumors concentrated on identifying high-risk mucosal types. OBJECTIVES: To determine the HPV type specific prevalence in different samples collected from the oral cavity of three groups of patients: (A) healthy (n=25); (B) non-malignant lesions (n=47); and (C) cancers (n=78). STUDY DESIGN: To evaluate the prevalence of HPV genotypes in the oral cavity, samples were analyzed by PCR with: MY09/MY11 followed by GP5+/GP6+, CP65/CP70 followed by CP66/CP69, and FAP59/FAP64 primers. The presence of viral transcripts was ascertained by RT-PCR with specific primers for the E7 region. RESULTS: Mucosal HPV types were associated with the presence of cancers. This trend was statistically significant if the analysis was performed for HPV 16 (p=0.04), which is the most prevalent type detected in oropharyngeal cancers. Conversely, cutaneous HPVs were associated with non-malignant lesions (p=0.007). The multiple correspondence analysis confirmed these data. Viral transcripts of only mucosal HPVs were detected in non-malignant lesions and cancers. CONCLUSIONS: Different types of HPVs infect the oral epithelium, but only the mucosal types, particularly HPV 16, are clearly associated with tumors. The discovery that cutaneous HPVs are associated with potential malignant oral disorders brings other data to understand the significance of their presence in the oral cavity.

Persistence of HPV after radio-chemotherapy in locally advanced cervical cancer.

A causal association of high risk HPV persistent infections with cervical cancer is firmly established by epidemiological and experimental evidence. Since HPV is considered a necessary factor for cervix carcinoma development and disease severity, the HPV DNA persistence may represent an indicator of both therapy effectiveness and risk of recurrence. The presence of HPV in locally advanced cervical carcinoma was analysed at the beginning of therapy, shortly after treatment and during follow-up, in 18 patients with cervix carcinoma treated by radio/chemotherapy. Persistence of HPV DNA sequences was revealed in 62.5% (10/16) of HPV positive patients, in which the HPV type and its physical status were exactly the same as at the onset of therapy, even many years after surgery. Interestingly, in two patients the HPV18 sequence analysis detected the same point mutations in the samples before and after the chemotherapy, and during the follow-up. HPV DNA clearance was associated with a better patient outcome because the majority of the HPV cleared women showed a complete response (6/6), no disease recurrence (4/6), and are still alive. Nevertheless, statistically significant association was seen only with complete responses versus partial or no responses. In conclusion, we demonstrated that HPV DNA positive tumour cells might persist for years in the genital epithelia, even after the surgical removal of the cervix and that HPV DNA detection after therapy is a valid and significant (p=0.03) tool to assess the efficacy of the treatment.

Detection of bovine papillomavirus type 2 in the peripheral blood of cattle with urinary bladder tumours: possible biological role.

Bovine papillomavirus type 2 (BPV-2) infection has been associated with urinary bladder tumours in adult cattle grazing on bracken fern-infested land. In this study, we investigated the simultaneous presence of BPV-2 in whole blood and urinary bladder tumours of adult cattle in an attempt to better understand the biological role of circulating BPV-2. Peripheral blood samples were collected from 78 cattle clinically suffering from a severe chronic enzootic haematuria. Circulating BPV-2 DNA was detected in 61 of them and in two blood samples from healthy cows. Fifty of the affected animals were slaughtered at public slaughterhouses and neoplastic proliferations in the urinary bladder were detected in all of them. BPV-2 DNA was amplified and sequenced in 78 % of urinary bladder tumour samples and in 38.9 % of normal samples as a control. Circulating episomal BPV-2 DNA was detected in 78.2 % of the blood samples. Simultaneous presence of BPV-2 DNA in neoplastic bladder and blood samples was detected in 37 animals. Specific viral E5 mRNA and E5 oncoprotein were also detected in blood by RT-PCR and Western blot/immunocytochemistry, respectively. It is likely that BPV-2 can persist and be maintained in an active status in the bloodstream, in particular in the lymphocytes, as a reservoir of viral infection that, in the presence of co-carcinogens, may cause the development of urinary bladder tumours.

Molecular analyses and prognostic relevance of HPV in head and neck tumours.

HPV involvement in head and neck (HN) cancer is still under active investigation. Fresh frozen and archival clinical samples from 115 patients affected by HN carcinomas were analysed by PCR-based methods and direct sequencing. HPV types, intra-type variants, physical status, viral load and viral transcript presence were determined. HPV positivity was correlated with the main clinical-pathological features, including smoker and drinker status, and the clinical outcome. Twenty-one tumours were HPV positive (18.3%) with HPV16 being the most frequent type (n=14) followed by HPV6 (n=4), HPV33, HPV35, and HPV58 (n=1, each type). Tonsil carcinomas contained more high-risk HPV types (6/8; 75%) than all other sites (p=0.0004). HPV16 genome was integrated in all analysed tumours, as pure integrated form or mixed with concomitant episomal forms (4 cases). The viral load showed a wide variability (range, 0.7-485 copies per cell) with the highest value detected in a larynx tumour and the lowest one in a case of cancer of the oral cavity. In 9 HPV-positive samples where mRNA was available, transcripts of viral early oncogenes originating by integrated, episomal or mixed forms of the viral genome were found. A statistically significant correlation was evidenced between HPV and tumour differentiation, being the virus more associated with tumour grade G3/G4. Multivariate Cox regression analysis revealed that lymph-node and grade status were significant independent factors for a worse disease-free survival and overall survival, whereas the HPV status was associated with a better overall survival (OR, 0.33; 95% CI, 0.13-0.81; p=0.01). Taken together these results indicate that distinct pathological mechanisms for the malignant transformation in each single HN subsite should be taken in account; HPV molecular analyses should be considered a valid tool to distinguish subsets of oropharyngeal tumours and HPV presence could be useful for the prognostic assessment of HNSCC.

Bovine papillomavirus type-2 DNA and expression of E5 and E7 oncoproteins in vascular tumours of the urinary bladder in cattle.

Cattles suffering from chronic enzootic haematuria frequently develop urinary bladder tumours of both epithelial and mesenchymal origin mainly haemangioma and its malignant counterpart. The role of the bovine papillomavirus type-2 (BPV-2) and of its major transforming oncoprotein in naturally occurring urothelial carcinogenesis has been recently clarified. E5 interacts in vivo as in vitro with the beta receptor for the platelet-derived growth factor (PDGF). However, studies regarding tumours of mesenchymal origin such as those arising from blood vessels are lacking. We show that the BPV-2 is present in 100% of the vascular tumours of the urinary bladder examined. Twenty-six out of twenty-seven tumour samples (96%) expressed E5 while 20 out of 27 (74%) tumour samples expressed E7. The two viral oncoproteins were not expressed in normal endothelial cells. Additionally, they co-localize in neoplastic endothelial cells as demonstrated by confocal immunofluorescence. PDGFbeta receptor was also shown to be expressed and co-localizes with E5 in neoplastic blood vessels. Our results demonstrate, for the first time, that the BPV-2 is present in high percentage in tumours of mesenchymal origin arising in its natural host. Furthermore, the expression of the two viral oncoproteins confirm that the virus may have a causative role in the neoplastic process.