Vaginal intraepithelial neoplasia: risk factors for persistence, recurrence, and invasion and its management.

OBJECTIVE: Our purpose was to profile patients with vaginal intraepithelial neoplasia, evaluate the response to treatment and define risk factors for persistence and progression. STUDY DESIGN: We reviewed records and histopathology slides of 94 patients with vaginal intraepithelial neoplasia diagnosed from 1977 to 1986. For 74 patients with follow-up, we evaluated risk factors by univariate and multivariate analyses. RESULTS: Sixty-four of 94 patients (68%) had prior or concurrent anogenital squamous neoplasia, including 21 with invasive and 43 with intraepithelial. Twenty-three had prior radiotherapy, 10 had anogenital neoplastic syndrome, and 11 were immunosuppressed. In 52 of 74 treated patients (70%), vaginal intraepithelial neoplasia went into remission after a single treatment. In 18 patients (70%) vaginal intraepithelial neoplasia went into remission after a single treatment. In 18 patients (24%) recurrent vaginal intraepithelial neoplasia went into remission after chemosurgery, upper vaginectomy, or other treatments; in 4 (5%) it progressed to invasion. Significant multivariate risk factors for persistence or progression were multifocal lesions and anogenital neoplastic syndrome but not vaginal intraepithelial neoplasia grade, associated cervical neoplasia, or immunosuppression. CONCLUSIONS: Although most vaginal intraepithelial neoplasia goes into remission after treatment, 5% of cases may progress from occult foci to invasion in spite of close follow-up.

Ano-genital neoplasia in renal transplant patients.

Ano-genital neoplasia is about 20 x more common in renal transplant patients than the general population. Neoplasms in the immunosuppressed are more morbid and mortal because: patients are younger; tumors are more undifferentiated; they have more and larger foci; more sites are involved; neoplasms tend to persist, recur and progress; and there are more complications from treatments. Intraepithelial neoplasia engenders some morbidity. Invasion is rarer, but when it occurs, it is always morbid, and all too often mortal. Invasive ano-genital cancer is primarily preventable because the lower genital and anal tracts are accessible to inspection, cytologic screening, endoscopy and biopsy. Prime prevention is avoiding infection with the Human Papilloma Virus (HPV). Next best is detecting HPV/intraepithelial neoplasia early with frequent inspection, cytology and liberal biopsies; and then removing any condylomas or intraepithelial neoplasia that develop.

Characteristics of cervical intraepithelial neoplasia in women infected with the human immunodeficiency virus.

OBJECTIVE: Our purpose was to compare characteristics of cervical intraepithelial neoplasia in relation to human immunodeficiency virus infection among women referred to a public hospital colposcopy clinic with Papanicolaou smears showing cervical intraepithelial neoplasia. STUDY DESIGN: An evaluation of cervical intraepithelial neoplasia severity, lesion size, and vulvovaginal lesions with respect to human immunodeficiency virus status was performed. RESULTS: (1) Human immunodeficiency virus prevalence in 482 women with cytologic characteristics of cervical intraepithelial neoplasia was 13%. (2) In human immunodeficiency virus-infected patients, Papanicolaou smears were less adequate for evaluation and correlated less well with histologic findings than in uninfected patients (p < 0.05). (3) Human immunodeficiency virus-infected patients (n = 47) had more advanced cervical intraepithelial neoplasia, larger cervical lesions, and more associated vulvovaginal lesions than human immunodeficiency virus-negative patients (n = 161). In human immunodeficiency virus-positive women, the severity of cervical intraepithelial neoplasia was not associated with age, whereas in human immunodeficiency virus-negative women, increasing severity was significantly associated with increasing age. CONCLUSION: High rates of human immunodeficiency virus infection in inner-city colposcopy services and high-grade, extensive cervical lesions in infected women warrant special attention.

Anogenital papillomavirus infection and neoplasia in immunodeficient women: an update.

People with deficient cell-mediated immunity have an increased susceptibility to viral infections and certain cancers, particularly non-Hodgkin's lymphomas and cancers of the skin and anogenital region. These are linked to viral origins. Anogenital neoplasms in immunodeficient patients show a strong association with HPV infection; often occur at relatively young ages; involve multifocal locations; and tend to persist, recur, and progress rapidly, despite standard therapy. Because standard therapy of anogenital HPV lesions and neoplasia is often not effective in immunodeficient patients (and others with an anogenital neoplastic syndrome), special treatment is required. 5-Fluorouracil chemosurgery, followed by maintenance 5-fluorouracil therapy, is often effective and provides field suppression against recurrent HPV infection and neoplasia, with minimal damage to affected organs. After removal of all detectable HPV and neoplastic lesions, immunodeficient patients require close surveillance of the entire anogenital tract. Immunodeficient patients are an in vivo human laboratory in which to study the natural history of HPV and its oncogenic effects on the anogenital tract. The theory of HPV oncogenesis is supported by the evidence gathered from these patients.

The fallacy of the screening interval for cervical smears.

One hundred seventy-four women with invasive cervical carcinoma were interviewed about their cervical smear histories to assess the accuracy of self-reporting and to relate the smear history with patient and tumor characteristics. Patients reported significantly more frequent, more recent, and more normal smears than were documented in medical records. The interval between onset of cancer symptoms and previous smear correlated directly with advanced stage. Sixteen women with normal smears within 36 months had significantly more advanced cancers than did 25 women with recent abnormal smears. Women with recent normal and abnormal smears had similar sociodemographic and behavioral characteristics. Because of inaccuracies in patients' self-reported smear histories and cancers developing in women with recent normal smears, we conclude that a specific screening interval should not be relied upon.

Anogenital papillomavirus infection and neoplasia in immunodeficient women.

People with deficient cell-mediated immunity have an increased susceptibility to viral infections and certain cancers, particularly large cell lymphomas and cancers of the skin and anogenital region. All are linked to viral origins. Neoplasms in the immunodeficient patient often occur at a relatively young age, involve multifocal locations, tend to persist, recur, and progress rapidly. Anogenital neoplasms show a strong association with HPV infection and also persist, extend, and progress, in spite of standard therapy. Since standard therapy of anogenital HPV infection and neoplasia is often not effective in immunodeficient patients (and others with an anogenital neoplastic syndrome), special treatment is required. 5-Fluorouracil chemosurgery, followed by maintenance 5-fluorouracil therapy, is effective and provides field suppression against recurrent HPV infection and neoplasia, with minimal damage to affected organs. After removal of all detectable HPV infection or neoplastic lesions, immunodeficient patients require close surveillance of the entire anogenital tract. Immunodeficient patients are an in-vivo human laboratory in which to study the natural history of HPV and its oncogenic effects on the anogenital tract. The theory of HPV oncogenesis is supported by the evidence gathered from these patients.

Human papillomavirus and lower genital neoplasia in renal transplant patients.

Lower genital cytopathology was evaluated in 105 immunosuppressed renal transplant recipients. Evidence of human papillomavirus infection was found in 17.5% and of lower genital neoplasia in 9.5%. The rate of the virus infection in the immunosuppressed was nine times greater than in a general population and 17 times greater than in a matched immunocompetent population. The rate of cervical neoplasia was 16 times greater than in a general population and nine times greater than in a matched immunocompetent population. In one-third of patients with human papillomavirus lesions and one-half of patients with neoplastic lesions, multiple lower genital sites were also involved. Of risk factors evaluated, only the number of sexual partners was associated with the development of human papillomavirus/lower genital neoplasia.

The relationship between human papillomavirus and lower genital intraepithelial neoplasia in immunosuppressed women.

In a group of 20 immunosuppressed women with lower genital neoplasia, evidence of associated human papillomaviral infection was found in all patients on the basis of the histologic identification of koilocytes in the upper strata of areas of mild or moderate dysplasia. Immunohistochemical study of similar areas disclosed human papilloma structural antigens in the lesions in 60%, while 50% had lesions in which human papilloma virions were detected by the electron microscope. An abnormal immunologic status, indicated by an altered T-helper/T-suppressor ratio, a deficient response to mitogenic stimulation, or both, was confirmed in 80% of the patients studied. Twelve of the 20 patients had unusually persistent and recurrent intraepithelial neoplasia, and in one the disorder progressed to invasive epidermoid carcinoma. The progressive behavior of human papillomavirus-associated neoplasia in these immunosuppressed patients might represent an accelerated version of the long-term course of such lesions in immunocompetent hosts.

Association of human papillomavirus infection with cervical intraepithelial neoplasia.

Human papillomavirus infections of the cervix were assessed in patients attending a colposcopy clinic. Of 348 patients with cervical biopsies, 134 (38.5%) had human papillomavirus infections, and of 251 patients with cervical intraepithelial neoplasia (CIN) 112 (44.6%) had human papillomavirus. The majority of patients with human papillomavirus had concurrent CIN (83.6%; 112/134). Patients with human papillomavirus were significantly younger than patients without human papillomavirus (24.4 versus 29.9 years mean age; P less than .001), had significantly milder degrees of CIN (84% versus 43% mild/moderate dysplasia; P less than .001), and had a significantly lower mean number of pregnancies (2.16 versus 3.05; P less than .001). A matched pairs analysis of 69 pairs showed the same distribution of CIN in both human papillomavirus and nonhuman papillomavirus patients. Electron microscopy of human papillomavirus--specific koilocytes confirmed the presence of human papillomavirus particles in the nuclei.

5-fluorouracil/chemosurgery for intraepithelial neoplasia of the lower genital tract.

Sixteen patients with lower genital intraepithelial neoplasia were treated by 5-fluorouracil (5-FU)/chemosurgery: colposcopically directed excision of neoplastic epithelium pretreated with topical 5-FU. 5-FU loosens the neoplastic epithelium, facilitating its removal from the underlying stroma in a safe, minimally traumatic fashion. 5-FU/chemosurgery was undertaken in patients with vaginal neoplasia or those with lower genital neoplasia who were immunosuppressed or had a neoplastic syndrome, because conventional methods are often difficult or inadequate for these problems. In all 16 patients, the neoplasia went into remission. Two immunosuppressed patients developed recurrences of lesser dysplasia when 5-FU maintenance therapy was interrupted because of pregnancy. It was found that 5-FU/chemosurgery, followed by monthly 5-FU maintenance, may be the best treatment for intraepithelial neoplasia of the vagina or lower genital intraepithelial neoplasia in patients who are immunosuppressed or have a neoplastic syndrome.

The significance of atypical vessels and neovascularization in cervical neoplasia.

The relationship between atypical vessels seen colposcopically and dysplasia, carcinoma in situ (CIS), microinvasion, and frank invasion was studied quantitatively. No atypical vessels were found with dysplasia, but 2.8% of patients with CIS had atypical vessels. Half of the patients with microinvasion and all of the patients with frank invasion, in whom the entire zone of transformation was viewed, had atypical vessels. Eight-two percent of the patients with atypical vessels had invasion. The conclusions are: (1) Atypical vessels are not present with dysplasia and rarely present with CIS. (2) Atypical vessels may be associated with microinvasion, but are required for frank invasion to occur. (3) Because atypical vessels are usually associated with invasion, which can be in or near the field of atypical vessels, diagnosis cone biopsy should be performed if atypical vessels are seen and colposcopic biopsies do not show frank invasion. (4) Microinvasion without atypical vessels may be a localized disease.

A colposcopic study of the effect of IUDs on cervical epithelium.

A case-control study was undertaken to investigate the effects of intrauterine contraceptive devices (IUDs) on the histology of cervical epithelium. Ninety-one women who had used IUDs for 2--13 years were case subjects and were compared with the same number of women who had never used any form of contraception (control subjects). Two subgroups were investigated, group A and group B. Group A consisted of 53 IUD users and 53 controls coming to family planning and gynecology clinics, and group B consisted of 38 IUD users and 38 controls from dysplasia clinics. Cervical cytology and colposcopically directed cervical biopsies were taken in all women. There was no difference between IUD users and control subjects in the proportion or the severity of dysplasia in either group A or group B. There was no evidence of an increase in the prevalence or severity of dysplasia with prolonged IUD use.