High-risk human papillomavirus (HPV) in parotid lesions.

Although several studies have reported that oropharyngeal infection with HPV may predispose to tumorigenesis, little is known about the etiological factors of salivary gland tumors and the presence of HPV. We studied 9 parotid lesions for HPV infection including an oncocytoma, an acinic cell carcinoma, a high-grade adenocarcinoma, a low-grade polymorphous adenocarcinoma, a Warthin's tumor and 2 pleomorphic adenomas, a lymphoepithelial cyst and a lipoma of the parotid gland. DNA was extracted from formalin-fixed and paraffin-embedded tissue sections. Solution PCR for HPV detection was performed using the GP5+/GP6+ primers, while HPV typing was carried out by multiplex PCR for HPV6, 11, 16, 18, and 33; positive samples were recorfirmed by PCR with specific primers for each type. Quantitative real-time PCR for the high-risk HPV genotypes 16, 18, 31, 33, 35, 52, 58 and 67 was also performed to quantitate the viral load. Finally, in situ PCR was employed with HPV16-specific primers by direct-detection method. Seven of the 9 parotid lesions were HPV positive while 6 of these 7 had been infected by HPV16 and/or HPV18 oncogenic types. High viral load of highrisk genotypes of HPV was found in the oncocytoma, in one of the pleomorphic adenomas, and in the Warthin's tumor. Finally, in situ PCR indicated that HPV16 amplification occurred in the salivary gland tumors. This is the first time that highrisk HPV genotypes are detected in these histological types of parotid lesions, suggesting the possible involvement of the virus in the disease.

Identification of novel prognostic markers in cervical intraepithelial neoplasia using LDMAS (LOH Data Management and Analysis Software).

BACKGROUND: Detection of Loss of Heterozygosity (LOH) is one of the most common molecular applications in the study of human diseases, in particular cancer. The technique is commonly used to examine whether a known tumour suppressor gene is inactivated or to map unknown tumour suppressor gene(s). However, with the increasing number of samples analysed using different software, no tool is currently available to integrate and facilitate the extensive and efficient data retrieval and analyses, such as correlation of LOH data with various clinical data sets. RESULTS: An algorithm to identify prognostic disease markers is devised and implemented as novel software called LDMAS. LDMAS is a software suite designed for data retrieval, management and integrated analysis of the clinico-pathological data and molecular results from independent databases. LDMAS is used in stratification of disease stages according to clinical stage or histological features and correlation of various clinico-pathological features with molecular findings to obtain relevant prognostic markers such as those used in predicting the outcome of cervical intraepithelial neoplasia (CIN). This approach lead to the identification of novel prognostic cervical cancer markers and extraction of useful clinical information such as correlation of Human Papilloma Virus (HPV) status with CIN lesions. CONCLUSIONS: A novel software called LDMAS is implemented and used to extract and identify prognostic disease markers. The software is used to successfully identify 4 novel prognostic markers that can be used to predict the outcome of CIN. LDMAS provides an essential platform for the extraction of useful information from large amount of data generated by LOH studies. LDMAS provides three unique and novel features for LOH analysis: (1) automatic extraction of relevant data from patient records and reports (2) correlation of LOH data with clinico-pathological data and (3) storage of complex data in flexible format. The first feature automates the creation of database of clinically relevant information from huge amount of data, the second feature extracts useful biomedical information such as prognostic markers in CIN and the third feature simplifies the statistical analyses of the data and allows non-statisticians to carry out the analysis. Additionally, LDMAS can be used to extract clinically useful markers from other diseases and interface to high throughput genotyping analysis software such as GDAS used to generate LOH data from Affymetrix GeneChip Mapping arrays.

Cervical cancer screening.

Although primary prevention of human papillomavirus (HPV) infections that are causally associated with invasive cervical cancer may be within our grasp, it is unlikely that these approaches will replace existing cervical cancer screening strategies for many years. Experts agree and data support periodic cytology screening for young-adult women using one of several technologies. Recent analyses of cost-effectiveness suggest that the addition of molecular HPV DNA testing for women aged over 30 years may allow the screening interval to be lengthened to 3 years for most women. Women at high risk for HPV infection and its associated cellular atypias warrant closer monitoring and follow-up. These patients would include organ transplant recipients, women exposed to diethylstilbestrol (DES), and HIV-infected women.

Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival.

Human papillomavirus (HPV) is more commonly found in tonsillar cancer than in other head and neck cancers. The importance of HPV status in tonsillar cancer for prognosis remains unclear. The aim of the present study was to investigate the frequency of HPV in tonsillar cancer and to correlate the presence of HPV with tumor stage, nodal status, grade of differentiation, risk of relapse, and survival. HPV DNA and HPV type were determined, using PCR, in pre-treatment biopsies from 60 cases of primary tonsillar cancer. All patients had undergone full-dose radiotherapy, 45% as the only treatment modality, and 55% in combination with surgery. HPV 16 was detected in 43% (26/60) of the cancers including 1 double infection of both HPV 16 and HPV 33. Patients with HPV(+) tonsillar cancer showed less risk of relapse within 3 years after diagnosis, with a better odds ratio of 4.18 as compared with HPV(-) patients (p = 0. 025). Furthermore, cause specific survival was significantly (p = 0. 047) better in patients with HPV(+) tonsillar carcinomas. At 3 years after diagnosis the survival rate was 65.3% in the HPV(+) group and 31.5% in the HPV(-) group, and at 5 years the survival rate was 53. 5% and 31.5%, respectively. The better outcome for patients with HPV(+) tonsillar cancer was independent of TNM stage, nodal status, gender and age. These results indicate that HPV status is a significantly favorable prognostic factor in tonsillar cancer and may be used as a marker in order to optimize the treatment of patients with this type of cancer.