Levine_Handbook for Principles and Practice of Gynecologic O

Chapter 4 Preinvasive Lesions of the Genital Tract 81 risk of developing cervical dysplasia and squamous cell carcinoma. Immunosuppression is a strong risk factor for the development of both CIN and cervical cancer; solid organ transplant recipients and HIV-infected women have higher rates of preinvasive HPV-associated lesions. In studies of renal transplant patients, transplant recipients have a relative risk of 13.6 for the development of CIN 3 compared to women in the general population. A Swedish study of solid organ transplant recipients found that the rates of vulvar malignancy were more than 25 times higher than that of the general population. Additionally, a large cohort study of American transplant recipients demonstrated that the rate of vulvar malignancy was higher in the women than was that of cervical cancer. This may reflect improved cervical cancer surveillance in this patient population. Over the last decade, it has become widely accepted that there is an asso ciation between cervical disease and infection with HIV. In a large prospec tive U.S.-based study, CIN 3 or worse was found in 5% of HIV-infected women compared to 2% of HIV-negative women. Invasive cervical cancers that develop in HIV-infected women act aggressively and respond poorly to standard forms of therapy. CD4 count and HIV RNA levels correlate with high-risk HPV positivity, and invasive cervical cancer has been desig nated as an AIDS case–defining illness by the Centers for Disease Control and Prevention. Treatment of HIV-positive women with highly active anti retroviral therapy (HAART) is associated with better CIN outcomes and improves life expectancy in HIV-positive women but has not been shown to change the incidence or persistence of HPV infections. Papillomaviruses are a diverse group of viruses that are widely distributed in mammals and birds. They are double-stranded DNA viruses that infect epithelial cells of skin and mucous membranes. To date, 120 papillomavi rus types have been identified. Over 40 types of HPV that infect the epi thelium of the anogenital tract have been described, and these different types of HPV tend to be associated with different types of epithelial lesions. HPV 6 and 11 are the most common HPV types found in association with benign exophytic condylomata of the male and female anogenital tracts in adults, whereas cervical dysplasia is associated with different HPV types. HPV types are categorized into “high risk” or “low risk” based on the rel ative risk of being associated with cancer (Table 4.2). A meta-analysis of the distribution of HPV types in CIN 2,3 lesions demonstrated that HPV 16 is identified in 45.3%, HPV 18 in 6.9%, and HPV 31 in 8.6%. Virology Papillomaviruses are naked DNA viruses composed of a double-stranded circular DNA genome and a protein coat containing 72 capsomeres of the viral L1 and L2 capsid proteins. The 8,000 base pair genome contains eight open reading frames encoding the viral proteins E1, E2, E4, E5, E6, E7, L1, and L2. The oncogenic potential of HPV types is attributed to the ability Human Papillomavirus Classification

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