Lower genital tract neoplasia in women with HIV infection

Women who are infected with human immunodeficiency virus (HIV) are at greater risk for the development of lower genital tract neoplasia than are HIV-negative women. Among HIV-positive women, those who are more severely immunosuppressed appear to be at higher risk for cervical intraepithelial neoplasia (CIN), also known as squamous intraepithelial lesions (SILs). Women who are HIV-positive also are more likely than HIV-negative women to have multifocal lower genital tract neoplasia. Cervical cancer is one of the most important acquired immune deficiency syndrome (AIDS)--related malignancies in women. Cancer and intraepithelial neoplasia of the lower genital tract can be persistent, progressive, recurrent, and difficult to treat in HIV-positive women. The most effective method for treating SILs has not been determined. Regular performance of Pap smears in HIV-positive women is of critical importance, as is careful examination of the entire lower genital tract. Also, women with high-grade intraepithelial or cervical cancer should be tested for HIV.     

Trends in squamous cell carcinoma of the vulva: the influence of vulvar intraepithelial neoplasia

OBJECTIVE: To determine trends in the clinicopathology of vulvar squamous cell carcinoma over the past 2 decades, with particular reference to the possible effects of the increasing incidence of vulvar intraepithelial neoplasia (VIN) during this time. METHODS: Two cohorts of 56 and 57 women with squamous cell carcinoma of the vulva and separated by at least 2 decades were reviewed retrospectively. Pathologic specimens were analyzed concurrently. RESULTS: In the 1965-1974 cohort, only one of 56 patients was younger than 50 years of age at the time of presentation, whereas in the 1990-1994 cohort, 12 of 57 (21%) were younger than 50 years of age (P = .001). Ten of 13 women younger than 50 years of age, compared with 13 of 100 of women 50 years of age or older, had warty or basaloid VIN associated with their invasive carcinoma (P < .001). Cigarette smoking and multiple lower genital tract neoplasia were both significantly more common in women younger than 50 years of age (P < .001). CONCLUSION: Over the past 2 decades, a subset of women younger than 50 years of age with squamous cell carcinoma of the vulva has emerged. Most of these carcinomas appear to arise in a field of warty or basaloid VIN. This suggests that the increasing incidence of VIN seen in young women during the past 2 decades is being reflected now in VIN-associated squamous cell carcinoma of the vulva in younger women.     

Cervical intraepithelial neoplasia in HIV seropositive patients

In order to assess the frequency of cervical intraepithelial neoplasia (CIN) in a high risk population, 32 women infected with human immunodeficiency virus (HIV), with no AIDS-related symptoms, underwent colposcopic, cytologic and histologic examinations of the uterine cervix. In seven cases (21.9%) cervical smears showed dysplasia and in nine cases (28.1%) histologic evaluation indicated CIN. No invasive carcinomas were observed. In seven of the nine women CIN was associated with lesions due to human papillomavirus infection (HPV). These data confirm that HIV-positive women are at increased risk for developing neoplasias in the lower genital tract and are in need of regular and careful cytologic and, in particular, colposcopic and histologic examinations.     

Intraepithelial neoplasia of the vulva

Intraepithelial neoplasia of the vulva is being seen with increasing frequency. Awareness of this should prompt the clinician to carefully inspect the vulva on all patients. Reports strongly suggest a relationship between infection with human papillomavirus and vulvar intraepithelial neoplasia. The frequency with which this disease progresses to invasive carcinoma is unknown at present. However, it is obvious that it does occur. Both the warty and basaloid types of vulvar intraepithelial neoplasia are associated with HPV infection and are often associated with invasive squamous cell carcinoma of the vulva demonstrating similar morphologic characteristics. These changes are seen more often in younger women who smoke than in the older nonsmoking woman whose lesions do not appear to be HPV related. Both local excision and the carbon dioxide laser are effective for treating vulvar intraepithelial neoplasia. The choice of which approach to take depends upon the location and size of the lesion or lesions. Whichever approach is utilized, preservation of the normal vulvar anatomy and function are of paramount importance.     

Anogenital papillomavirus infection and neoplasia in immunodeficient women

This article reviews the impact of infection with human immunodeficiency virus (HIV) on HPV infections and HPV-associated lesions of the female anogenital tract. Studies investigating HPV infections in HIV-seropositive women are presented as well as the possibility that HIV can influence HPV expression directly through molecular interactions between viral genes and indirectly through immunosuppression. Studies linking HIV infection to invasive cervical cancer and cervical intraepithelial neoplasia are reviewed; recommended protocols for cervical cancer screening in HIV-seropositive women for cervical disease also are presented.     

Distinct manifestations of human papillomaviruses in the vagina

To clarify the pathogenic relationships between human papillomavirus (HPV) and vaginal intraepithelial neoplasia (VAIN), we examined 71 vaginal biopsy specimens by histopathology and immunohistochemistry and analyzed the presence of HPV DNA by blot hybridization at Tm - 40 degrees C using an HPV 58 probe (PBM-58 method). We found 27 cases of VAIN in patients with previous hysterectomy or antecedent or concomitant cervical intraepithelial neoplasia (CIN) and 44 cases of VAIN in patients without any abnormal findings on the cervix and the vulva. Histopathologically, 53 of 71 cases were graded as VAIN I and 15 and 3 cases were VAIN II and III, respectively, while 59 cases showed positivity for HPV capsid antigen by immunohistochemistry. Using the PBM-58 method, all 71 VAIN cases harbored a single HPV type at more than 1,000 viral copies per cell. We identified 15 different types (HPV 16, 18, 30, 31, 35, 40, 42, 43, 51, 52, 53, 54, 56, 58 and 66). Furthermore, we molecularly cloned 7 novel prototypes (HPV 59, 61, 62, 64, 67, 69 and 71) from VAIN I. Our results are strongly indicative that HPVs are etiologic agents of VAIN, like in the case of CIN. The distinct manifestations of HPV infection in the vagina are discussed in comparison with those in the cervix.     

Fine mapping of the hereditary sensory neuropathy type I locus on chromosome 9q22.1-->q22.3: exclusion of GAS1 and XPA

BACKGROUND: Knowledge about the natural course of HPV infection is still limited. In this study we investigated the presence of HPV DNA after treatment and clinical clearance of infection. METHODS: Eighty-two women treated for genital HPV infection at the STD clinic in Uppsala were consecutively selected for the study. After treatment with podophyllotoxin, and in some cases laser vaporization, a cell sample was taken at the follow-up visit 6-12 months after clinical clearance of the lesions as evaluated by colposcopy. Samples were analysed with PCR to detect HPV DNA. As a reference group, women treated for cervical intraepithelial neoplasia (CIN) with laser surgery, either with cone biopsy or vaporization, were followed-up after 6 months for the presence of HPV DNA. RESULTS: Six to 12 months after clinical clearance of HPV infection, 39 (48%) of the women showed detectable HPV DNA in cell samples from the cervix. Of these, 26 (67%) were found to harbor high risk HPV, six (15%) low risk, and seven (18%) either had more than one HPV type or HPV that could not be classified. All but three of the women treated for CIN (90%) were negative for HPV DNA. CONCLUSION: After clinical clearance of genital HPV infection half of the women had detectable HPV DNA. This does not necessarily imply that transmission to a new partner may occur, but indicates this possibility. Only 10% of the CIN treated women harbored HPV DNA in the cell samples in spite of showing high risk HPV infection before treatment.     

Regional distribution and incidence of human papillomavirus infections among heterosexual men and women with multiple sexual partners: a prospective study

OBJECTIVE: To assess prevalence, incidence and potential risk factors of human papillomavirus (HPV) infection among heterosexual men and women with multiple partners and to identify niches of HPV-infection. DESIGN: A prospective study of heterosexual men and women with multiple partners attending an STD clinic as participants in a study on HIV from May 1988 until January 1991. Routine STD examination and physical examination using colposcopy were performed, interviews with standardised questionnaires were administered. Specimens for HPV DNA detection by polymerase chain reaction were collected from multiple sites of the genital, anorectal and oral regions. In women cervical cytology was performed. SETTING: The STD Clinic of the Municipal Health Service of Amsterdam. PARTICIPANTS: 162 women and 85 men entered the study, 110 women and 48 men were followed up. RESULTS: At entry of the study 37 (23%) women and 24 (28%) men were found positive for HPV DNA at any site. Only in one woman was oral presence of HPV DNA found during follow-up. Abnormal cervical cytology was observed in four women. In multivariate analysis, diagnosis of condylomata [odds ratio (OR) 5.61, 95% confidence interval (CI) 1.86 to 16.90)], reporting genital dermatological abnormalities (OR 3.72, 95% CI 1.38 to 9.99) and age (OR per year 0.93, 95% CI 0.88 to 0.99) predicted independently the presence of HPV DNA in women at entry of the study. In women 59 of the 99 (60%) HPV infections were observed in the genital region and 40% in the anorectal region: in men these figures were 65% and 35%, respectively. The incidence of HPV infection was 47.1 and 50.5 per 100 person-years for women and men respectively. At least 20/99 (20%) infections in women were intermediate or long persistent and only 3/48 (6%) HPV infections in men (P = 0.03). No risk factor for persistency could be determined, either in women or in men. CONCLUSIONS: HPV infection was found to be a multicentric genital and/or anorectal event both in women and men. The oral presence of HPV DNA was detected only once in one of the participants. In women persistent HPV infection was more common than in men. Independent predictors for presence of HPV DNA in women were diagnosis of condylomata acuminata, reporting genital dermatologic abnormalities and age. Incidence of HPV infection in women turned out to be 47.1 infections per 100 person-years and for men 50.5 per 100 person-years.     

Reflex human papillomavirus deoxyribonucleic acid testing in women with abnormal Papanicolaou smears

OBJECTIVE: The study examined interrelationships between sensitivity and specificity of "reflex human papillomavirus deoxyribonucleic acid testing" from liquid-based cervical cytologic specimens by means of receiver operator characteristics curves. STUDY DESIGN: A cohort study was performed on 265 women evaluated by colposcopy because of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion found on Papanicolaou smear. RESULTS: At a positive threshold of 0.2 pg/ml (1000 copies of human papillomavirus per test), human papillomavirus deoxyribonucleic acid testing detected 86% of women with cervical intraepithelial neoplasia and 93% of women with high-grade cervical intraepithelial neoplasia with a specificity of 30%. Decreasing the sensitivity of the human papillomavirus test to 1 pg/ml (5000 copies of human papillomavirus per test) improved the specificity of a positive result to 44% but decreased the clinical sensitivity to 78% for cervical intraepithelial neoplasia grade 2 or 3. Relationships between sensitivity and specificity were influenced by patient age and referral diagnosis. For example, limiting the analysis to only women with a referral for atypical squamous cells of undetermined significance found on Papanicolaou smear and a positive human papillomavirus test threshold of 0.5 pg/ml produced a sensitivity of 90% for cervical intraepithelial neoplasia grade 2 or 3 and a test specificity of 55%. CONCLUSION: Human papillomavirus deoxyribonucleic acid testing of residual cellular material from liquid cytologic specimens appears to be more appropriate for older women (>30 years old) and women with atypical squamous cells of undetermined significance, as opposed to low-grade squamous intraepithelial lesion, on their Papanicolaou smears.     

Metals pollution in marine sediments of the United Arab Emirates creeks along the Arabian Gulf shoreline

In order to evaluate the association between seropositivity for herpes simplex virus (type 1 and type 2) and cervical intraepithelial neoplacia (CIN), we analysed data from a population-based case-control study of CIN grade II-III which included Norwegian women aged 20 to 44 years, 94 cases and 228 controls. Our objectives were to determine if HSV-1 and/or HSV-2 seropositivity were independent risk factors for CIN, taking human papillomavirus exposure into account, and to elucidate the combined effect of HPV positivity and seropositivity for HSV In logistic regression analyses, the association between HSV-2 or HSV-1 seropositivity and CIN II-III was not explained by HPV (adjusted OR 3.0; 95%, CI 1.3-7.2 and adjusted OR 3.3; 95% CI 1.3-8.4, respectively). In analyses restricted to HPV-16 DNA-positive individuals, seropositivity for HSV-2 increased the risk of CIN (OR 11.1; 95% CI 1.2-105.7), whereas HSV-1 seropositivity was not significantly associated with CIN. In women positive for other HPV types, only HSV-1 seropositivity was associated with CIN (OR 8.5; 95% CI 1.3-55.8). In analyses of the HPV-16-seropositive individuals, neither HSV-1 nor HSV-2 seropositivity was associated with CIN. Compared to the reference group of jointly unexposed subjects, the HPV-16 DNA-positive women who were anti-HSV-2 negative had an increased risk of CIN (OR 29; 95% CI 12-67), whereas the risk in women who were both HPV-16 DNA-positive and HSV-2 was OR=247 (95% CI 31-1996). The estimate of interaction was strong, but did not reach significance, and our findings may suggest that the combined effect of the two viruses is of aetiological importance in cervical carcinogenesis. Furthermore, the results indicate that HPV DNA positivity is not sufficient to explain the sexual behaviour-associated risk of cervical neoplasia and that further studies on the role of genital HSV (type 1 as well as type 2) and other STDs are warranted.     

Immunoglobulin G responses against human papillomavirus type 16 virus-like particles in a prospective nonintervention cohort study of women with cervical intraepithelial neoplasia

BACKGROUND: Infection with cancer-linked human papillomavirus (HPV) types such as HPV type 16 (HPV16) is the most important risk factor in the development of cervical cancer. It has been shown that immunoglobulin G (IgG) antibody responses against HPV16 virus-like particles (VLPs) are specifically associated with genital HPV16 infection. PURPOSE: The aim of this study was to determine the temporal relationships between the presence of HPV16 VLP-specific IgGs, HPV16 infection patterns, and the course of premalignant cervical disease. METHODS: Plasma samples from 133 women who had been diagnosed originally with mild to moderate cervical dyskaryosis and enrolled in a prospective non-intervention cohort study conducted in Amsterdam, The Netherlands, from 1991 through 1996 were analyzed for the presence of HPV16 VLP-specific IgGs by use of an enzyme-linked immunosorbent assay. A detailed analysis was performed on 43 women with different HPV16 infection patterns during a follow-up period of 10-34 months. Progression or regression of cervical intraepithelial neoplasia (CIN) lesions was monitored by cytologic and colposcopic testing at intervals of 3-4 months. HPV typing in cervical smears was performed by use of a polymerase chain reaction-based assay. Statistical analysis of the serologic data was performed by use of the Mann-Whitney U test or 2 x 2 table analyses. RESULTS: The presence of HPV16 VLP-specific IgGs in the plasma of the patients was found to be associated with the presence of HPV16 DNA in the cervical smear. Significantly higher proportions of patients with persistent HPV16 infections (i.e., who were polymerase chain reaction positive in three to 11 consecutive tests) than of patients with cleared HPV16 infections were found to be positive for the presence of HPV16 VLP-specific IgGs (18 [69.2%] of 26 versus nine [28.1%] of 32, respectively; P = .003). HPV16 VLP-specific IgGs were consistently detected in all women (n = 11) who were persistently HPV16 DNA positive during follow-up and whose disease ultimately progressed to CIN III (histologically diagnosed severe dysplasia or carcinoma in situ). CONCLUSION: HPV16 VLP-specific IgG responses are present in the plasma of a majority of patients with persistent HPV16 infections and histologically confirmed high-grade lesions but only in a smaller subset of patients with cleared HPV16 infections and either normal cervical histology or low-grade CIN lesions. IMPLICATIONS: These results suggest that HPV16 VLP-specific antibodies are not responsible for the clearance of virally induced CIN lesions but that they might, in patients with persistent HPV16 infections, be indicative of an increased cervical cancer risk.     

Detection of human papillomaviruses (HPV-16,18) in cervical smears by in situ hybridization

The rate of human papillomaviruses (HPV) 16 and 18 infections were measured in 109 women with histologically or cytologically determined lesions of the uterine cervix and in 42 healthy women. Cervical swabs were taken as the source of the target viral DNA. In situ hybridization with biotinylated probes was used. HPV-16 was the predominant type in patients and in healthy women. The percentage of positive cases was the highest in cervical cancer patients: 43.3% in squamous cell carcinoma and 33.3% in adenocarcinoma followed by cervical intraepithelial neoplasia (CIN), III, II (21.4%), CIN I (14.3%) and low grade squamous intraepithelial lesions (13.6%). HPV-18 type was detected in a lower percentage in the three groups of patients. In healthy women HPV-16 was determined in 12% and HPV-18 in 4.8%. We believe that the described noninvasive method of obtaining clinical material should be the method of choice for estimating papillomavirus infections in patients and in the general population. Our results are in agreement with suggestions that HPV genotype could be an important prognostic indicator in cervical carcinoma.     

Clinicopathological features of human papilloma virus associated squamous cell carcinomas of the vulva

OBJECTIVE: To investigate the relationship between human papilloma virus (HPV) status and clinicopathological features of vulva carcinoma and its clinical significance. METHODS: Histological sections of 37 cases of vulval carcinoma were subclassified. Standard PCR (HPV types 6/11, 16, 18) were applied to formalin fixed, paraffin wax sections. RESULTS: There were 24 cases of keratinizing squamous cell carcinoma (KSC), 7 cases of basaloid carcinoma (BC) and 6 cases of warty carcinoma (WC). HPVs, Mainly HPV 16, were detected in 10 of the 37 cases, and all of them were women with BC and WC types. Although BC and WC constituted 35% of the total number of cases, the HPV detective rate was significantly higher than that of KSC (83.3% vs 0.0%), and the tumors were frequently accompanied by valvar intra-epithelial neoplasm (VIN). Clinically, women with BC and WC were younger than women with KSC (mean age at diagnosis for WC, BC and KSC were 36.7, 58.9, 63.3 years respectively). Besides, the incidence of lymph node metastasis in BC and WC were lower than that in KSC (7.6% vs 25.0%). BC and WC were more likely to have another invasive or noninvasive squamous neoplasm of the cervix and vagina (3/13 vs 0/24), and recurrence rate was higher (12.5% vs 7.7%). However, their survival rates following surgical treatment of recurrences were also higher. Squamous cell carcinoma of the vulva are etiologically diverse tumors which have different clinical and pathological profiles. CONCLUSION: It is suggested that an etiological classification of squamous carcinoma of the vulva may at least be grouped at present into a small but substantial proportion (BC and WC) related to HPV and the majority portion (KSC) of unknown etiology.     

Female genital schistosomiasis due to Schistosoma haematobium. Clinical and parasitological findings in women in rural Malawi

A total of 51 women with urinary schistosomiasis haematobium were examined in order to identify diagnostic indicators for female genital schistosomiasis (FGS). Patients were selected at random from the outpatient department of the Mangochi District Hospital, Malawi. The medical histories were recorded according to a pre-designed questionnaire and the women were subjected to a thorough gynaecological examination including colposcopy and photographic documentation of lesions. Microscopy of genital biopsies revealed that 33 of the 51 women had S. haematobium ova in cervix, vagina and/or vulva in addition to the presence of ova in urine. The most sensitive diagnostic procedure was beside microscopic examination of a wet cervix biopsy crushed between two glass slides, which revealed 25 of the 33 genital infections. There was a significant correlation between the size of genital lesions and the number of ova counted per mm2 of crushed tissue. Women with FGS had significantly more tumours in the vulva than women with schistosomiasis limited to the urinary tract. Most of the observed genital pathology could easily be identified by the naked eye, but colposcopic examination yielded valuable additional information like the demonstration of neovascularisation around cervical sandy patches. Few of the symptoms previously regarded as indicators for FGS could be linked to the presence of schistosome ova in genital tissue. Husbands of infertile women with FGS had children with other women significantly more often than husbands of women who only had urinary schistosomiasis. This, together with the finding that the majority of the divorced women had FGS, indicates that the manifestation of this disease may have implications for the marital and sexual life of the affected women.     

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.     

Usefulness of hybrid capture HPV DNA assay as a diagnostic tool for human papillomavirus infection

The purpose of this study was to determine the usefulness of the hybrid capture HPV DNA assay, a new nonradioactive solution hybridization assay, as a diagnostic tool for human papillomavirus infection. In a total of 234 women, samples for the hybrid capture assay and polymerase chain reaction (PCR) assay were obtained by wiping a swab across the cervix and external os (either a Dacron swab or a cotton swab was used). The papanicolaou smear test (Pap smear) was carried out on all 234 women. Tissue samples for biopsy were obtained by colposcopy from 118 of the women. Fisher exact test was used for statistical analyses. Using the hybrid capture assay, HPV DNA of high- and intermediate-oncogenic-risk type was detected in 23 (13.9%) of 166 samples from women with Pap smear Class I or II, and 48 (70.6%) of 68 with Pap smear Class III, IV or V (p < 0.0001). The HPV DNA type was detected in 18 (29.0%) of 62 samples from those with no evidence of cervical intraepithelial neoplasia and 44 (78.6%) of 56 with cervical intraepithelial neoplasia or squamous cell carcinoma (p < 0.0001). Correlation of the test results between the hybrid capture test and PCR was determined by using the 217 samples in which both test results were available (PCR test results were not obtainable in 17 samples. When PCR is set as a gold standard, the hybrid capture test has high sensitivity (74.6%) and specificity (92.7%). These findings suggest that the hybrid capture HPV DNA assay is a useful method for diagnosing HPV infection in the clinic.     

Determinants of genital human papillomavirus infection among cytologically normal women attending the University of New Mexico student health center

OBJECTIVES: To confirm the risk factors for genital human papillomavirus (HPV) infection. GOAL OF THIS STUDY: To investigate risk factors for HPV detection apart from the correlated risk factors for cervical neoplasia. STUDY DESIGN: Cervical human papillomavirus (HPV) DNA was assessed in 357 cytologically normal women attending the University of New Mexico student health center. Cervical swab samples were obtained for HPV DNA detection and typing using a PCR-based DNA amplification system. Possible determinants of cervical HPV were examined including age, ethnicity, history of sexually transmitted disease, oral contraceptive use, smoking, age at first intercourse, lifetime number of sex partners, marital status, and history of pregnancy. RESULTS: A 44.3% overall prevalence of cervical HPV was observed. On univariate analysis, factors associated with increasing HPV prevalence included higher lifetime number of sex partners and single marital status. After adjustment for potential confounding variables, we found that HPV prevalence increased with higher lifetime number of sexual partners. CONCLUSION: These findings, along with those from the companion reports in this issue of the journal, support the sexual route of transmission of the virus.     

Occurrence of human papillomavirus infection in cervical intraepithelial neoplasia. A retrospective histopathological study of 317 cases treated by laser conization

The aim of the study was to compare the histological outcome of the cone specimens with the diagnoses of the preoperative biopsies, to assess the distribution of histological features consistent with human papillomavirus (HPV) infection and, finally, to analyse the impact of cellular HPV features on classification of cervical intraepithelial neoplasia (CIN). The study comprised a population of 317 women treated for CIN by laser conization during the period 1983-85. A total of 634 cervical specimens (317 preoperative biopsies and their corresponding cones) were studied retrospectively for CIN classification and examined for morphological signs of HPV infection. For presentation of the results, we used a modified terminology for CIN. Low-grade (LG) CIN included borderline lesions and CIN I, while high-grade (HG) CIN included CIN II and CIN III. The blinded histopathological review revealed HG CIN both in the preoperative biopsies and the cones in 71% of the cases. LG CIN or benign lesions were found in the preoperative biopsies and their corresponding cone specimens in 6% of the study population. HPV features were present in 65% of the preoperative biopsies, and were most prevalent in women under 29 years of age (p < 0.001). Thirteen percent of the total biopsy material was downgraded. The downgrading was most prevalent among original CIN II (p = 0.009) and HPV-negative biopsies (p < 0.001). This study demonstrates that CIN lesions are frequently associated with HPV features, which are significantly more prevalent in the youngest women. Concomitant HPV features do not influence the CIN classification.     

New vision for the role of emergency medical services

Genital human papillomavirus (HPV) infection is the major causal factor of cervical intraepithelial neoplasia (CIN). The potential role of nutrition as an additional, independent risk factor for CIN has not been appropriately addressed in the context of HPV. This case-control study evaluated the etiologic role of HPV in terms of viral type and load and examined the association between CIN and plasma levels of micronutrients adjusting for HPV. Cases (n = 378) with histo-pathologically confirmed CIN and controls (n = 366) with no history of abnormal Pap smears were recruited from colposcopy and gynecology clinics, respectively. Risk of CIN was significantly increased among women who were infected with multiple HPV types (odds ratio [OR] = 21.06), a high viral load (OR = 13.08) and HPV 16 (OR = 62.49). After adjusting for HPV positivity and demographic factors, there was an inverse correlation between plasma alpha-tocopherol and risk of CIN (OR = 0.15). Plasma ascorbic acid was protective at a high level of > or = 0.803 mg/dl (OR = 0.46). CIN was not associated with plasma retinol and beta-carotene levels. The effect of genital HPV infection on CIN development is highly influenced by oncogenic viral type and high viral load. Vitamins C and E may play an independent protective role in development of CIN that needs to be confirmed in prospective studies.     

The management of DES-exposed women: one physician's approach

The female offspring of DES-treated mothers are examined cytologically and colposcopically annually, starting at the age of seven years no treatment is indicated until a colposcopic atypical transformation zone occurs. With its occurrence all the abnormal epithelium(squamous or columnar) is excised from the vagina and cervix under colposcopic guidance in the hospital or in the office under local anesthesia. The procedures are done in stages to minimize scarring and to eliminate the possibility of vaginal-cervical adhesions or vaginal shortening. The finding of an incidence of 47% of cervical or vaginal intraepithelial neoplasia in 34 patients aged 10 to 26 years so treated to date indicates a high risk of potential candidacy for squamous carcinoma of the vagina or cervix in later years.