NATURAL HISTORY OF GENITAL HUMAN PAPILLOMAVIRUS IN RENAL TRANSPLANTS

生殖器人类乳头瘤病毒（HPV）感染是非常常见的。这种性传播疾病可能影响多达70%的性活跃妇女在她们生命中的某个时候。疾病表现因HPV类型、感染部位和宿主因素而异。HPV 6型和11型引起生殖器疣和低级别上皮内瘤变。有令人信服的证据表明，作为多步骤癌变过程的一部分，16、18和31型可促进高级别上皮内瘤变和浸润性肛门生殖器癌的发展。宿主对HPV的主要防御似乎是细胞介导的免疫。以细胞免疫功能受损为特征的疾病，如器官移植的医源性免疫抑制和人类免疫缺陷病毒感染，与生殖器疣和肛门生殖器恶性肿瘤的频率和严重程度增加有关。在这项研究中，我们将确定一组60名妇女在术前接受同种异体肾移植时生殖器HPV感染的患病率；还有三组30名接受同种异体移植的女性，她们分别接受同种异体移植不到一年，一到五年，五年以上。这些队列将每隔四个月随访一年，以确定发病率数据。患者将接受常规盆腔检查，包括肛门外生殖器检查和窥镜检查。由HPV感染引起的外部异常将进行活检。子宫颈抹片检查；宫颈衣原体和单纯疱疹病毒培养；及进行宫颈清洗，以作HPV检测。聚合酶链反应（PCR）将用于HPV检测，分型将通过标准技术进行。此外，患者将被要求在每次就诊时完成性史。免疫抑制数据将从患者的病历中获得。有外部病变的患者将采用标准疗法进行治疗。宫颈抹片检查异常的病人将被转介到妇产科作进一步的评估和治疗。将描述HPV感染的临床、细胞学和组织学表现。这项研究的数据将为免疫功能低下人群中生殖器HPV感染的自然史提供重要的见解。

Genital human papillomavirus (HPV) infection is exceedingly common. This sexually transmitted disease may affect as many as 70% of all sexually active women at some time in their lives. Disease manifestations vary depending on the HPV type, the site of infection and host factors. HPV types 6 and 11 cause genital warts and low grade intraepithelial neoplasias. There is compelling evidence that types 16, 18 and 31 contribute to the development of high grade intraepithelial neoplasias and invasive anogenital cancers as part of the multistep process of carcinogenesis. The primary host defense against HPV appears to be cell mediated immunity. Conditions characterized by impairment of cellular immunity such as the iatrogenic immunosuppression of organ transplantation and human immunodeficiency virus infection are associated with an increase in the frequency and severity of genital warts and anogenital malignancies. In this study we will establish the prevalence of genital HPV infection in a group of 60 women at the time they receive their renal allografts in the immediate preoperative period; and three groups of 30 women each who have had established allografts for: less than one year, one to five years, and greater than five years respectively. These cohorts will be followed at fourth month intervals for a year to determine incidence data. Patients will undergo routine pelvic examination including inspection of the external anogenital areas and speculum examination. External abnormalities attributed to HPV infection will be biopsied. A pap smear; cervical cultures for chlamydia and HSV; and cervical washings for HPV testing will be obtained. The polymerase chain reaction (PCR) will be used for detection of HPV and typing will be performed by standard techniques. In addition, patients will be asked to complete a sexual history at each visit. Immunosuppression data will be obtained from the patient's medical chart. Patients with external lesions will be treated with standard therapies. Patients with abnormal pap smears will be referred to the Department of Obstetrics and Gynecology for further evaluation and treatment. Clinical, cytologic and, when indicated, histologic manifestations of HPV infection will be described. Data from this study will provide important insights into the natural history of genital HPV infection in a select immunocompromised population.