Cell-Mediated Immune Response to Human Papillomavirus Infection

Abstract

Acquisition of human papillomavirus (HPV) results in an infection of variable duration which may or may not be associated with clinically apparent lesions. Lesions caused by skintropic HPV types generally manifest as cutaneous warts and most often resolve over a period of months to years. On the other hand, anogenital infections are more likely to remain clinically inapparent. The development of DNA amplificationbased tests has demonstrated that anogenital infections are quite common and generally self-limited. For example, we and others have shown by PCR testing of multiple samples collected at different points in time-that 70 to 90% of sexually active adolescents and young women who develop an incident cervical HPV infection will show clearance of infection within 12 to 30 months (47,61,94). The factors influencing the natural history of these infections are not well understood. Given that persistent anogenital infection with oncogenic HPV types is associated with increased risk of neoplasia and invasive cancers (22,59,70,71,94,124) and that cervical carcinoma remains a leading cause of death among women in developing countries (129), understanding these factors is of considerable importance.Substantial effort has been directed recently at understanding the role of the host's immune response in the natural history of HPV, and in particular, anti-viral, cell-mediated immunity. Empirical evidence for the importance of cell-mediated immunity in control of HPV infection comes from an extensive body of literature documenting the increased prevalence of HPV infection and associated disease among immunosuppressed populations, including those with iatrogenic immunosuppression such as renal transplant recipients and individuals with human immunodeficiency virus (HIV) infection. Sillman and coauthors (128) reported in 1984 on 20 immunosuppressed women with various causes of immunosuppression who had lower genital neoplasia, describing evidence of associated HPV infection in all 20. Penn, in 1986, reported a 100-fold increase in cancer of the vulva and anus in renal transplant recipients (111). In the 1990s, as molecular testing for HPV infection came into its own, several reports confirmed increased incidence of HPV infection (50) and associated morbidities, including warts (77) and cervical squamous intraepithelial lesions (SIL) (104), among immunosuppressed renal transplant recipients.The most persuasive evidence for the association between cellular immune defects and HPV infection and related morbidities comes from persons with HIV infection. Such individuals show increased prevalence of anogenital HPV infection (31, 32, 60, 105-107) as well as longer periods of HPV persistence (31,40,46,90,136). In addition, infection with multiple HPV types and with oncogenic types are more common (9,31,46,78,90,107,136). Associations between markers of HIV disease status (e.g., viral load and CD4 lymphocyte count) and HPV infection have been inconsistent. Most studies have suggested that advanced disease and greater immunological ...

Expression of dendritic cell lysosome-associated membrane protein and dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin in condyloma acuminatum lesions

“…8 During the initial stage, HPV infects primitive basal keratinocytes and these cells are activated to produce high amounts of chemokines, cytokines, and growth factors, which cause genital warts. 9 DCs (such as Langerhans cells) take up and process undefined antigens, then migrate to draining lymph nodes where they present the antigen to activate CD4þ T cells (T-helper cells). After activation, CD4þ T cells secrete chemokines and cytokines to regulate the functions of other immune cells.…”

Human Papillomavirus

“…Bunlar; kanser açısından düşük riskli HPV'ler (6,11,40,42,43,44,54, 55 ve 62), olası yüksek riskli HPV'ler (26,53 ve 66) ve yüksek riskli HPV'ler (16 başta olmak üzere 18,31,33,35,39,45,51, 56, 58, 59, 68, 73 ve 82) olarak gruplandırılmaktadırlar 6,7 .…”

“…Benign metaplastik veya malign epitelyum gibi daha fazla nükleer yoğunluğu olan böl-geler, ısıyı alttaki stromaya geçirmek yerine daha fazla yansıtarak, pembe veya kırmızı yerine beyaz (asetobeyaz) olarak görünür. Nükleer dansitenin arttığı, yüksek dereceli CIN lezyonlarında epitel, diğer lezyonlarda görüldüğünden daha opak olarak gözlenir 33 .…”

Human Papillomavirus: Biology and Pathogenesis

“…In immunosuppressed patients, HPV infection frequently leads to the appearance of abundant HPV-induced lesions, indicating that the immune system acts to limit HPV infection (Scott et al, 2001). Therefore, in order to persist, HPV must actively suppress both innate and adaptative immune response.…”