Mem Inst Oswaldo Cruz. 2005 Feb;100(1):1-12. Epub 2005 Apr 12.
Immune response in cervical dysplasia induced by human papillomavirus: the influence of human immunodeficiency virus-1 co-infection -- review.
Nicol AF, Fernandes AT, Bonecini-Almeida Mda G. Departamento de Microbiologia, Imunologia e Parasitologia, Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz, Av. Brasil 4365, 21040-900 Rio de Janeiro, RJ, Brazil.
Human immunodeficiency virus (HIV-1) has become an important risk factor for human papillomavirus (HPV) infection and the development of HPV associated lesions in the female genital tract. HIV-1 may also increase the oncogenicity of high risk HPV types and the activation of low risk types. The Center for Disease Control and Prevention declared invasive cervical cancer an acquired immunodeficiency virus (AIDS) defining illness in HIV positive women. Furthermore, cervical cancer happens to be the second most common female cancer worldwide. The host's local immune response plays a critical factor in controlling these conditions, as well as in changes in the number of professional antigen-presenting cells, cytokine, and MHC molecules expression. Also, the production of cytokines may determine which arm of the immune response will be stimulated and may influence the magnitude of immune protection. Although there are many studies describing the inflammatory response in HPV infection, few data are available to demonstrate the influence of the HIV infection and several questions regarding the cervical immune response are still unknown. In this review we present a brief account of the current understanding of HIV/HPV co-infection, emphasizing cervical immune response.
Int J Gynaecol Obstet. 2005 May;89 Suppl 2:S55-9.
Preventing cervical cancer in low-resource settings: How far have we come and what does the future hold?
Tsu VD, Pollack AE. Program for Appropriate Technology in Health (PATH), 1455 NW Leary Way, Seattle, WA 98107-5136, USA.
The Alliance for Cervical Cancer Prevention (ACCP) came together in 1999 to answer key research questions and to advocate for greater global and national interest in reducing the heavy burden of morbidity and mortality caused by this preventable disease. Visual inspection with acetic acid (VIA), visual inspection with Lugol's iodine (VILI), and human papillomavirus (HPV) tests have been shown to be viable alternatives to traditional cytology. ACCP experience confirmed that cryotherapy is a safe and effective method that is acceptable to women and can be delivered by a range of health providers, including nonphysicians. Programs can maximize coverage by accommodating local needs and involving community leaders and women in planning and implementation. Advocacy efforts have led to significant policy changes and galvanized support for cervical cancer prevention. Despite the prospect of new HPV vaccines, screening will be needed for at least the next 30-40 years. Our experience has shown that with creativity, flexibility, and well-focused use of resources, the inequitable burden of cervical cancer borne by women in poor countries can be sharply reduced.
Vaccine. 2005 May 25;23(28):3634-41.
Immune responses induced by lower airway mucosal immunisation with a human papillomavirus type 16 virus-like particle vaccine.
Nardelli-Haefliger D, Lurati F, Wirthner D, Spertini F, Schiller JT, Lowy DR, Ponci F, Grandi PD. Department of Gynecology, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland.
Cervical cancer results from cervical infection by human papillomaviruses (HPV), especially HPV16. Previous studies have shown that intramuscular vaccination of women with an HPV16 virus-like particle (VLP) vaccine induced a strong IgG response and protected against genital HPV16 infection. However, an alternative route of administration that avoids parenteral injection while inducing mucosal immunity might facilitate vaccine implementation in some settings, and partially overcome the substantial variation in HPV16 antibodies at the cervix seen in ovulating women. In this study, women were vaccinated with escalating doses of HPV16L1 VLPs via nasal nebulisation, bronchial aerosolisation, or a combination of intramuscular and aerosol vaccination. The alternative routes of vaccination were well tolerated and many of the volunteers who received aerosol vaccinations exhibited serum antibody titers that were comparable to those induced by intramuscular vaccination. A mucosal immune response was induced by aerosol vaccination as demonstrated by the induction of anti-HPV16 VLP IgA secreting cells in PBMC and SIgA in secretions. Our data suggest that aerosol administration of HPV VLPs may represent a potential alternative to parenteral injection.
Cytopathology. 2005 Feb;16(1):7-12.
Clinical relevance of human papillomavirus testing in cytopathology.
Brink AA, Zielinski GD, Steenbergen RD, Snijders PJ, Meijer CJ. Department of Pathology, Vrij Universiteit Medical Center, Amsterdam, The Netherlands.
Cancer of the uterine cervix is the second most common cancer in women worldwide. Currently, cervical screening is based on cytology alone. Because infection with high-risk human papillomavirus types (hrHPVs) is a necessary cause of cervical cancer, it has been postulated that screening might become more efficient when it is based on combined cytology and hrHPV testing. In this review we will discuss the advantages of added HPV tests in cervical cancer screening, as a quality control for false-negative smears, in triage of women with equivocal smears, in follow-up of women treated for CIN3 or cervical cancer and for the detection of cervical adenocarcinoma.
Natural history and possible reactivation of human papillomavirus in human immunodeficiency virus-positive women.
Strickler HD, Burk RD, Fazzari M, Anastos K, Minkoff H, Massad LS, Hall C, Bacon M, Levine AM, Watts DH, Silverberg MJ, Xue X, Schlecht NF, Melnick S, Palefsky JM. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Ave., Belfer #1308, Bronx, NY 10461, USA. strickle@aecom.yu.edu
BACKGROUND: Little is known in human immunodeficiency virus (HIV)-positive women about how the combination of plasma HIV RNA level and CD4+ T-cell count is associated with the natural history of human papillomavirus (HPV) infection or about HPV reactivation--whether it occurs and with what frequency in HIV-positive women. METHODS: HIV-positive (n = 1848) and -negative (n = 514) women were assessed at semiannual visits (total person-years = 5661) for cervicovaginal HPV with polymerase chain reaction assays and for squamous intraepithelial lesions (SILs) by Pap smear. We studied the prevalent detection of HPV and SILs with generalized estimating equations and the incident detection and persistence of HPV and SILs with multivariable Cox models. All statistical tests were two-sided. RESULTS: We observed a strong interaction between the associations of CD4+ and plasma HIV RNA strata with both prevalent (P(interaction) = .002) and incident (P(interaction) = .001) detection of HPV. Indeed, the hazard ratio for incident HPV detection peaked between 4.0 and 5.0, with either a CD4+ count of less than 200 cells per mm3 or an HIV RNA level of more than 100,000 copies per mL. Although incident HPV detection in all women was associated with the number of recent sex partners (P(trend)<.001), 22% of sexually inactive HIV-positive women with a CD4+ count of less than 200 cells/mm3 also had at least one incidentally detected HPV type. The association between CD4+/HIV RNA strata and HPV persistence was statistically significantly smaller (P<.001) than for incident HPV detection. SIL prevalence, incident detection, and persistence had similar associations with CD4+/HIV RNA strata as HPV (above). CONCLUSION: In HIV-positive women, plasma HIV RNA level and CD4+ count in combination appear to have a strong and statistically interactive association with incident detection of HPV, some of which may reflect HPV reactivation (e.g., in sexually inactive women). The more moderate association between HIV coinfection and HPV persistence could partly explain why cervical cancer rates have not reached more epidemic proportions in HIV-positive women.
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