Cervical cancer is the possible outcome of genital infection with high-risk human papillomavirus (HPV) and is preceded by a phase of persistent HPV infection during which the host immune system fails to eliminate the virus. Fortunately, the majority of genital HPV infections are cleared before the development of (pre)malignant lesions. Analysis of CD4+ T-helper (Th) immunity against the E2, E6,...

Clinical studies suggest that responses to HPV16 E6E7L2 fusion protein (TA-CIN) vaccination alone are modest, and GPI-0100 is a well-tolerated, potent adjuvant. Here we sought to optimize both the immunogenicity of TA-CIN via formulation with GPI-0100 and treatment of HPV16+ cancer by vaccination after cisplatin chemotherapy. HPV16 neutralizing serum antibody titers, CD4+ T cell proliferative a...

Human papillomavirus type 16 (HPV16) is the primary etiologic agent for greater than 50% of all cervical carcinomas. Expression of the HPV16 E6 and E7 oncoproteins is under control of the upstream regulatory region (URR), which contains a myriad of transcription factor binding sites, including 7 half sites for NFI. These NFI binding sites were used as probes in electrophoretic mobility shift as...

High-risk human papillomavirus (HR-HPV) has been recognized as a major causative agent for cervical cancer. Upon HPV infection, early genes E6 and E7 play important roles in maintaining malignant phenotype of cervical cancer cells. By using clustered regularly interspaced short palindromic repeats- (CRISPR-) associated protein system (CRISPR/Cas system), a widely used genome editing tool in man...

Cellular tumor suppressors p53 and Rb play an important role in controlling cell proliferation. Inactivation of these tumor suppressor proteins can occur by gene mutation or by association with oncoproteins from the small DNA tumor viruses. One function of p53 is in regulating cell cycle check-point control after DNA damage. To dissect the pathways by which p53 and Rb may act, the E6 and E7 onc...

We have previously shown that a novel DNA vaccine technology of codon optimization and the addition of ubiquitin sequences enhanced immunogenicity of a herpes simplex virus 2 polynucleotide vaccine in mice, and induced cell-mediated immunity when administered in humans at relatively low doses of naked DNA. We here show that a new polynucleotide vaccine using the same technology and encoding a f...

Human papillomavirus (HPV) type 16 infection is strongly associated with the development of cervical carcinoma (CxCa) in women. The HPV16-derived oncoproteins E6 and E7, responsible for both onset and maintenance of malignant transformation, are expressed constitutively in CxCa cells and represent tumor-associated Ags. As a result, E6 and E7 constitute potential targets for adoptive CTL-mediate...

Cervical cancer is a leading cause of death due to cancer among women worldwide. Using transgenic mice to dissect the contributions of the human papillomavirus (HPV) 16 E6 and E7 oncogenes in cervical cancer, E7 was identified previously to be the dominant oncogene. Specifically, when treated with exogenous estrogen for 6 months, E7 transgenic mice developed cancer throughout the reproductive t...

Although HPV16 transforms infected epithelial tissues to cancer in the presence of several co-factors, there is insufficient molecular evidence that poor nutrition has any such role. Because physiological folate deficiency led to the intracellular homocysteinylation of heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) and activated a nutrition-sensitive (homocysteine-responsive) posttranscr...