HPV Virus Treatments - Methods

Sirianni N, Wang J, Ferris RL. Department of Otolaryngology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.

High risk HPV types 16 and 18 are associated with cervical cancer and squamous cell carcinoma of the head and neck (SCCHN). Cidofovir is an antiviral drug used to treat HPV-induced laryngeal papillomatosis and other viral infections, with initial reports suggesting activity in cervical carcinoma cells. We investigated the effects of Cidofovir on a naturally HPV-16-transformed SCCHN cell line (UPCI:SCC090), in comparison with a cervical carcinoma cell line (CasKi) of similar viral characteristics, to evaluate its therapeutic potential. HPV-16 gene transcription was only marginally reduced, and the antiviral and p53 restorative effects were modest in SCC90 cells. However, combination with irradiation enhanced the effects of Cidofovir treatment on these cells. Several days of treatment were required for this effect, which may limit its clinical applicability. Future therapies for HPV-associated tumors may include intralesional antiviral therapy in combination with radiation therapy, but optimization for clinical utility is needed.

JAMA. 2005 Mar 23;293(12):1471-6.

Incidence of cervical squamous intraepithelial lesions associated with HIV serostatus, CD4 cell counts, and human papillomavirus test results.

Harris TG, Burk RD, Palefsky JM, Massad LS, Bang JY, Anastos K, Minkoff H, Hall CB, Bacon MC, Levine AM, Watts DH, Silverberg MJ, Xue X, Melnick SL, Strickler HD. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA. tharris@aecom.yu.edu

CONTEXT: Recent cervical cancer screening guidelines state that the interval between screenings can be safely extended to 3 years in healthy women 30 years or older who have normal cytology results and have negative test results for oncogenic human papillomavirus (HPV) DNA. OBJECTIVE: To determine the incidence of squamous intraepithelial lesions (SILs) in HIV-seropositive women with normal cytology results, by baseline HPV DNA results. DESIGN, SETTING, AND PATIENTS: Participants were HIV-seropositive (n = 855; mean age, 36 years) and HIV-seronegative (n = 343; mean age, 34 years) US women with normal baseline cervical cytology who were enrolled in the Women's Interagency HIV Study (WIHS), a large, multi-institutional prospective cohort study. Since their recruitment during 1994-1995, WIHS participants have been followed up semi-annually with repeated Pap smears for a median of 7 years. MAIN OUTCOME MEASURE: The cumulative incidence of any SIL and high-grade SIL or cancer (HSIL+) was estimated according to baseline HPV DNA results, stratified by HIV serostatus and CD4 T-cell count. RESULTS: Development of any SIL in women with negative HPV results (both oncogenic and nononcogenic) at 2 years was as follows: in HIV-seropositive women with CD4 counts less than 200/microL, 9% (95% CI, 1%-18%); with CD4 counts between 200/muL and 500/microL, 9% (95% CI, 4%-13%); and with CD4 counts greater than 500/microL, 4% (95% CI, 1%-7%). The CIs for these estimates overlapped with those for HIV-seronegative women with normal baseline cytology who were HPV-negative (3%; 95% CI, 1%-5%), indicating that at 2 years, there were no large absolute differences in the cumulative incidence of any SIL between groups. Furthermore, no HPV-negative participants in any group developed HSIL+ lesions within 3 years. Multivariate Cox models showed that on a relative scale, the incidence of any SIL among HIV-seropositive women with CD4 counts greater than 500/microL (hazard ratio [HR], 1.2; 95% CI, 0.5-3.0), but not those with CD4 counts less than or equal to 500/microL (HR, 2.9; 95% CI, 1.2-7.1), was similar to that in HIV-seronegative women. CONCLUSION: The similar low cumulative incidence of any SIL among HIV-seronegative and HIV-seropositive women with CD4 counts greater than 500/microL and who had normal cervical cytology and HPV-negative test results suggests that similar cervical cancer screening practices may be applicable to both groups, although this strategy warrants evaluation in an appropriate clinical trial.

J Clin Virol. 2005 Mar;32 Suppl 1:S72-81.

Immune control of human papillomavirus (HPV) associated anogenital disease and potential for vaccination.

Stern PL. CR UK Immunology Group, Department of Immunology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, UK. pstern@picr.man.ac.uk

This review discusses: (1) immune mechanisms relevant to the natural control of a human papillomavirus (HPV) infection; (2) viral strategies to evade or subvert immune attack; (3) the significance of immune escape as a feature of the evolution of invasive cancer; (4) vaccine strategies for prevention and/or therapy. HPV infection and associated malignancy can induce humoral and cellular immunity to capsid and oncogene viral proteins, but it is not always clear whether such responses are a consequence of the disease rather than the resolving factor(s). Prophylactic strategies are utilising virus-like particles (VLP) composed of the L1 viral capsid protein to induce neutralising antibodies, while therapeutic approaches are aimed at generating specific T cells targeted at the viral E6 and/or E7 oncogenes. Thus far, HPV VLP vaccines have proved clinically efficacious in the early clinical trials to prevent infection. Different types of therapeutic vaccines including peptide, protein, DNA or viral vector encoded have proved safe and immunogenic in patients, although there is often no correlation with clinical outcome. Understanding the equilibrium between viral and immunological factors will be important in providing the appropriate tools to evoke effective prophylactic and therapeutic immunity. It seems likely that combined prophylactic and therapeutic vaccine approaches could offer the best prospect for any significant reduction in death from cervical cancer worldwide.

J Clin Virol. 2005 Mar;32 Suppl 1:S34-42.

The role of human papillomavirus testing in cervical screening.

Cuschieri KS, Cubie HA. Specialist Virology Centre, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK. Kate.Cuschieri@luht.scot.nhs.uk

Organised, cytology-based cervical screening has led to a reduction in deaths associated with cervical cancer. Human papillomavirus (HPV) is necessary for the development of cervical cancer and associated pre-cursor cervical intraepithelial neoplasia and accumulated evidence suggests that incorporation of HPV testing could further refine screening programmes. HPV testing is discussed in the context of primary screening, for triage, and as a test of cure of treatment and possible value in developing countries. The high negative predictive value of a "double negative" cytology and HPV result could allow considerable changes in policy such as increased intervals between screening rounds, adjustment of age ranges for testing and schedule for return to routine screening post treatment. HPV testing for the triage of women to colposcopy with borderline or atypical squamous cells of undetermined significance (ASCUS) cytology could be clinically effective, but may be limited in women with low-grade squamous intraepithelial lesions (LSIL) or mild dyskaryosis by high HPV prevalence. Markers of HPV persistence harbour enormous potential to identify women at greatest risk of disease progression. Due to the diversity of existing cytology-based screening programmes, full cost-effectiveness analyses of HPV testing should be performed and assessed within local contexts.

Infect Dis Obstet Gynecol. 2004 Sep-Dec;12(3-4):127-33.

Gynecologists' attitudes regarding human papilloma virus vaccination: a survey of Fellows of the American College of Obstetricians and Gynecologists.

Raley JC, Followwill KA, Zimet GD, Ault KA. Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.

BACKGROUND: Human papilloma virus (HPV) is the causative agent of cervical neoplasia and genital warts. A vaccine has recently been developed that may prevent infection with HPV. Vaccination for HPV may become a routine part of office gynecology. We surveyed members of the American College of Obstetricians and Gynecologists (ACOG) to determine their attitudes to HPV vaccination. METHODS: A survey was sent to Fellows of ACOG to evaluate gynecologists' attitudes. Vaccine acceptability was analyzed using 13 scenarios with the following dimensions and respective attributes: age of patient (13, 17 and 22 years); efficacy of vaccine (50% or 80%); ACOG recommendation (yes or no); and disease targeted (cervical cancer, warts or both). Each scenario was rated by means of an 11-point response format (0 to 100). Responses were evaluated using conjoint analysis. RESULTS: Of 1200 surveys that were sent out, 181 were returned and included in our analysis. ACOG recommendation was considered the most important variable in vaccine distribution (importance score = 32.2), followed by efficacy (24.5), age (22.4) and, lastly, disease targeted (20.9). Of these variables, higher efficacy was favored; preference was given to age 17 years, with a strong disinclination to vaccinate at age 13 years; and protection against cervical cancer, or genital warts, or both, was significantly favored over a vaccine against genital warts alone. Demographic characteristics of the gynecologists (i.e., age of physician, gender, practice setting and community size) did not play an important role in the decision to recommend vaccination. CONCLUSION: Professional society recommendation is important for acceptability of a potential HPV vaccine. Gynecologists are willing to include this vaccine in their office practice.

HPV Virus Treatments - Methods of HPV Treatment Links

HPV Maintenance - Here you can get some ideas on what HPV is and how to live with it.

HPV Treatment Reviews - Here you can find general characteristics of various medicines against HPV manifestations.