HPV Virus Medical Facts - Treatment

Cui Z, Huang L. Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh, 633 Salk Hall, Pittsburgh, PA, 15213, USA, leafh@pitt.edu.

With the successful identification of many tumor-specific antigens, tumor-associated antigens, and the potential of using unfractioned tumor cell derivatives as tumor antigens, a system and/or adjuvant that can deliver these antigens and help them to induce strong and effective anti-tumor immune responses is greatly needed. Previously, we reported that a MHC class I-restricted peptide epitope derived from human papillomavirus (HPV) 16 E7 protein, when incorporated into a clinically proven safe LPD (liposome-polycation-DNA) particle, was able to effectively eradicate tumors established in mice. Cervical cancer is the second most common cancer among women worldwide. HPV infection is clearly linked to this cancer. Vaccines based on the early (E) gene products of HPV could be effective in controlling it. However, besides the fact that epitope vaccines have many limitations particularly, concerning the diverse HLAs in humans, the use of the epitope as an antigen prevented us from fully characterizing the immune responses induced by the LPD as a vaccine carrier and/or adjuvant in previous studies. In the present study, by using the HPV 16 E7 protein as an antigen, we first showed that LPD, as a vaccine carrier and adjuvant induced strong and robust immune responses, both cellular and antibody. We then showed that immunization with LPD particles incorporated with either the wild type HPV 16 E7 protein or a potentially safer mutant induced strong immune responses that caused complete regressions of a model cervical cancer tumor established in murines. LPD could be a potent vaccine carrier and/or adjuvant for many antigens.

J Immune Based Ther Vaccines. 2005 Apr 20;3(1):2.

Kinetics and isotype profile of antibody responses in rhesus macaques induced following vaccination with HPV 6, 11, 16 and 18 L1-virus-like particles formulated with or without Merck aluminum adjuvant.

Ruiz W, McClements WL, Jansen KU, Esser MT. Vaccine and Biologics Research Merck Research Laboratories 466 Devon Park Dr, Wayne, PA 19087-8630 USA. mark_esser@merck.com.

BACKGROUND: Human papillomaviruses (HPV) are the most common sexually transmitted viruses. Infection of the cervical epithelium by HPVs can lead to the development of cervical cancer. Recent advances in vaccine research have shown that immunization with papillomavirus-like particles (VLPs) containing the major structural viral protein, L1 from HPV 16 can provide protection from the establishment of a chronic HPV 16 infection and related cervical intraepithelial neoplasia (CIN) in baseline HPV 16 naive women. METHODS: To better understand the quantitative and qualitative effects of aluminum adjuvant on the immunogenic properties of an HPV 6, 11, 16 and 18L1 VLP vaccine, we used an HPV-specific, antibody isotyping assay and a competitive immunoassay that measures antibodies to neutralizing epitopes to profile sera from rhesus macaques immunized with the HPV L1 VLP vaccine formulated with or without aluminum adjuvant. RESULTS: Immunization with VLPs formulated with the aluminum adjuvant elicited a significantly stronger immune response with higher peak antibody titers both at four weeks post vaccination (12.7 to 41.9-fold higher) as well as in the persistent phase at week 52 (4.3 to 26.7-fold higher) than that of VLPs alone. Furthermore, the aluminum adjuvant formulated HPV VLP vaccine elicited a predominantly T helper type 2 response, with high levels of IgG1 and IgG4 and low levels of IgG2. The vaccine also elicited high levels of serum IgA, which may be important in providing mucosal immunity to impart protection in the anogenital tract. CONCLUSION: These results show that the HPV 6, 11, 16 and 18 L1-VLP vaccine formulated with Merck aluminum adjuvant elicits a robust and durable immune response and holds promise as a vaccine for preventing cervical cancer.

Dermatol Clin. 2005 Apr;23(2):313-22.

Advances in antiviral therapy.

Wu JJ, Pang KR, Huang DB, Tyring SK. Department of Dermatology, University of California at Irvine, C340, Medical Science I, Irvine, CA 92697-2400, USA.

Infections with five of the herpesviruses (herpes simplex virus 1 [HSV-1], HSV-2, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus) are treated with topical or systemic antiviral therapies. There are more than 100 genotypes of human papillomaviruses (HPVs), which may manifest as warts, skin cancers, cervical cancer, anogenital cancers, and upper digestive tract cancers. Molluscum contagiosum (MC) is a common, benign viral infection of the skin. Immunomodulating agents, such as imiquimod, act on HPV and MC indirectly by inducing host immune responses, such as cytokines and cell-mediated immunity, and thereby reduce recurrences. There are multiple vaccines available for certain viral diseases and others in development for HSV-2 and HPV.

Eur J Immunol. 2005 May;35(5):1548-56.

Papillomavirus virus-like particles induce cytokines characteristic of innate immune responses in plasmacytoid dendritic cells.

Lenz P, Lowy DR, Schiller JT. Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, USA.

Human papillomavirus (HPV) virus-like particles (VLP) are being extensively tested as vaccines for the prevention of HPV-associated cervical cancer. Dendritic cells (DC) acquire and present antigens, initiating innate and adaptive immune responses. It has been shown previously that DC of the myeloid lineage are capable of generating adaptive immune responses to HPV VLP in vitro. However, the capacity of plasmacytoid DC (pDC) to acquire HPV VLP and the nature of the immune response generated have not been reported. In this study we found that freshly isolated as well as CpG-matured pDC bind papillomavirus VLP and that internalization occurs preferentially in the immature pDC. In contrast to myeloid DC, pDC did not undergo phenotypic maturation upon exposure to HPV16 VLP. However, HPV16 VLP induced pDC to secrete of IFN-alpha and IL-6, both cytokines that play a role in the generation of antibody responses, as well as TNFalpha and IL-8. Given that VLP do not contain viral nucleic acids, these results indicate that viral capsids alone may be capable of inducing cytokine production by pDC. Finally, CpG-activated pDC, but not pDC exposed to HPV16 VLP, activated lymphocytes to secrete IL-10 and low levels of IFN-gamma. Together these findings suggest a possible immunogenic effect of pDC in the setting of VLP vaccination.

Int J Gynecol Cancer. 2005 Mar-Apr;15(2):278-84.

Human papillomavirus status in advanced cervical cancer: predictive and prognostic significance for curative radiation treatment.

Lindel K, Burri P, Studer HU, Altermatt HJ, Greiner RH, Gruber G. Department of Radiation Oncology, Inselspital, University of Berne, Bern, Switzerland. katja_lindel@med.uni-heidelberg.de

Human papillomavirus (HPV) infection plays a major role in oncogenesis of squamous cell carcinoma of the cervix. This study was performed to investigate if HPV status and E2 gene integrity are prognostic parameters for clinical outcome and predictive for radiation response. Forty women with locally advanced cervical cancer treated with curative radiotherapy were analyzed for HPV infection and E2 gene integrity by multiplex polymerase chain reaction. Statistical analyses were performed for overall survival, disease-free survival (DFS), local progression-free survival, and treatment response (clinical complete remission). Twenty-eight (70%) of 40 carcinomas were HPV positive. The only significant factor for a better overall survival, DFS, and local progression-free survival was HPV positivity (P < 0.02, P= 0.02, and P < 0.05, log-rank, respectively). HPV-positive tumors had a significantly better clinical complete remission (67% vs 33%, P= 0.04, Fisher's exact test). An intact E2 gene region showed a trend for a better DFS (P= 0.1, log-rank). This study reveals HPV as an independent prognostic parameter for outcome and radiation response. Integration of the virus genome into host cell DNA might be a molecular target to determine the treatment response of HPV-positive cancers.

HPV Virus Medical Facts - Treatment for HPV Manifestations Links

Genital Warts and HPV FAQ - Here you can read about the biggest worry associated with HPV.

PapScreen - Information on treatment. Once all your test results are available, your doctor will be able to discuss the best treatment for you.