Over the past several decades, knowledge of the biology and epidemiology of human papillomavirus (HPV) infection has increased tremendously. However, there are still many unanswered questions concerning the interaction of the virus with its host. The virus has been identified as a necessary causal agent for cervical squamous neoplasia and has been linked to the development of neoplasia in several other mucosal sites. The viral oncogenes E6 and E7 are the major players in the virus' scheme to evade the immune system and use the host cell replication machinery to survive. Many risk factors for infection with HPV have been identified; however, the focus now centers on identifying risk factors for persistence of the infection as it is likely that transient infections play a very small role in the overall development of clinical disease. Prevention measures to date have centered around screening programs, mostly for cervical cancer, including the perfection of screening techniques and inclusion of molecular testing for HPV into screening regimens. The development of prophylactic and therapeutic vaccines has also increased as primary prevention measures appear to have the best hope for long-term effects on cancer incidence.

Progress toward a molecular characterization of cancer would have important clinical benefits; thus, there is an important need to image the molecular features of cancer in vivo. In this paper, we describe a comprehensive strategy to develop inexpensive, rugged and portable optical imaging systems for molecular imaging of cancer, which couples the development of optically active contrast agents with advances in functional genomics of cancer. We describe initial results obtained using optically active contrast agents to image the expression of three well known molecular signatures of neoplasia: including over expression of the epidermal growth factor receptor (EGFR), matrix metallo-proteases (MMPs), and oncoproteins associated with human papillomavirus (HPV) infection. At the same time, we are developing inexpensive, portable optical systems to image the morphologic and molecular signatures of neoplasia noninvasively in real time. These real-time, portable, inexpensive systems can provide tools to characterize the molecular features of cancer in vivo.

BACKGROUNDGreater than 40% of patients with squamous cell carcinoma (SCC) of the oral cavity have lymph node metastasis at the time of diagnosis and a 5‐year survival rate of less than 50%. Changes in gene expression that regulate metastasis of SCC to lymph nodes have not been identified.METHODSTo study metastasis of oral SCC, highly metastatic oral SCC cell lines from a poorly metastatic oral SCC cell line were established by in vivo selection using a lymph node metastatic mouse model. The metastatic potential of the cells was studied using Matrigel invasion and cell surface protein adhesion assays. mRNA and protein encoded from metastasis‐related genes in the metastatic derivatives and in their parental cells were examined using Northern blot analysis, immunoblotting, rapid analysis of gene expression, and a cDNA microarray technique.RESULTSThe in vivo selected metastatic cells showed much higher Matrigel invasion capability than the parental cells. They also showed alterations in their adhesion properties to three cell surface proteins. Comparison of metastatic and nonmetastatic cells revealed several significant alterations in the expression of metastasis‐related genes, including up‐regulation of the urokinase‐type plasminogen activator receptor, integrin β1, membrane type 1‐matrix metalloproteinase, and down‐regulation of protease‐activated receptor‐1.CONCLUSONSTo the authors' knowledge, the current study is the first to report on gene expression analysis using a lymph node metastatic mouse model of human oral SCC. The data suggest that certain alterations of metastasis‐related gene expression favor invasion of oral SCC and that cell surface proteins may play major roles in the metastasis of oral SCC to the lymph nodes. Cancer 2002;95:1663–72. © 2002 American Cancer Society.DOI 10.1002/cncr.10837

Productive Epstein-Barr virus (EBV) replication characterizes hairy leukoplakia, an oral epithelial lesion typically occurring in individuals infected with human immunodeficiency virus (HIV). Serial tongue biopsy specimens were obtained from HIV-infected subjects before, during, and after valacyclovir treatment. EBV replication was detected by Southern hybridization to linear terminal EBV genome fragments, reverse-transcriptase polymerase chain reaction amplification of EBV replicative gene transcripts, immunohistochemical detection of EBV replicative protein, and in situ hybridization to EBV DNA. EBV replication was detected in both hairy leukoplakia and normal tongue tissues. Valacyclovir treatment completely abrogated EBV replication in vivo, resulting in resolution of hairy leukoplakia when it was present. EBV replication returned in normal tongue epithelial cells after valacyclovir treatment. These data suggest that normal oral epithelium supports persistent EBV infection in individuals infected with HIV and that productive EBV replication is necessary but not sufficient for the pathogenesis of oral hairy leukoplakia.

No abstract