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PubMed1990

Human immunodeficiency virus infection and cervical neoplasia.

To determine the relationship between human immunodeficiency virus (HIV) infection and cervical neoplasia, the characteristics of invasive and preinvasive cervical disease in 114 patients of known HIV status were assessed. Seven of thirty-seven patients (19%) under age 50 with invasive cervical carcinoma were HIV-positive, including a 16-year-old with stage IIIB disease. HIV-positive patients had more advanced invasive cancer than HIV-negative patients. Disease persisted or recurred in all HIV-positive patients compared to 37% of HIV-negative patients. In HIV-positive patients, the median times to recurrence and death were 1 and 10 months, respectively. No HIV-positive patient had HIV-related symptoms. The mean T4:T8 cell ratio in HIV-positive patients was 0.49, compared to 1.86 in HIV-negative patients. The mean T4 cell count was 362/mm3 in HIV-positive and 775/mm3 in HIV-negative patients. Colposcopic evaluations of the lower genital tract of 77 patients with abnormal smears revealed higher-grade cytology and histology in 25 HIV-positive than in 52 HIV-negative patients. HIV-positive patients had significantly more multifocal/extensive lesions, multisite involvement, perianal involvement, evidence of human papillomavirus (HPV) infection, and associated gynecologic infections than HIV-negative patients. In areas at high risk for HIV infection, we must anticipate a high prevalence of HIV seropositivity in women with invasive cervical cancer. In the HIV-infected, cervical cancer is of advanced stage and responds poorly to therapy. Intraepithelial neoplasia in HIV-positive patients may be of higher grade than in HIV-negative patients, with more extensive involvement of the lower genital tract.

Adolescent↗
PubMed1990

Relationship between intraepithelial neoplasia of the cervix and the size and number of nucleolar organizer regions.

A silver colloid technique was applied to 18 colposcopic biopsies of the cervix. These comprised 7 cases of cervical intraepithelial neoplasia I (CIN I), 5 cases of CIN II, and 6 cases of CIN III. The nucleolar organizer regions subsequently visualized (AgNORs) were enumerated using an oil immersion lens. The maximum diameters of the AgNORs and aggregates thereof were measured, by hand, from carefully calibrated monochrome photographs. The mean numbers of AgNORs subsequently identified steadily increased, whereas the mean sizes of AgNORs decreased from CIN I to CIN III. In CIN I the mean AgNOR number was 2.3 (range 1.8-3.4) and the AgNOR mean maximum diameter (Dmax) was 1.28 microns (range 0.75-1.75). In CIN II the mean number was 3.5 (range 3.1-4.6) and the AgNOR Dmax was 0.98 micron (range 0.9-1.18). In CIN III the mean number was 4.7 (range 4.0-6.1) and the Dmax was 0.62 micron (range 0.51-0.9). CIN III could be distinguished from CIN I and CIN II on the basis of AgNOR sizes, and an inverse relationship between AgNOR numbers and sizes was established.

DNA, Neoplasm↗
PubMed1990

Topical treatment with human leukocyte interferon of HPV 16 infections associated with cervical and vaginal intraepithelial neoplasias.

The present placebo-controlled, double-blind trial was designed to determine the effect of potent human leukocyte interferon cream (IFN) on genital HPV 16 (high-risk-type) infections associated with cervical intraepithelial neoplasia (CIN) and/or vaginal intraepithelial neoplasia (VAIN). Twenty women were treated with either IFN or placebo cream. The daily dose of IFN was 9 x 10(6) IU. The patients applied the cream deep into the vagina every night for 2-week courses 1 week apart. The entire treatment period was 12 months. On the basis of colposcopical, cytological, and histological examinations, 4 of 9 patients in the IFN group and 7 of 10 patients in the placebo group showed clinical remissions at the end of the trial. However, the virological studies gave a different picture. After treatment, 6 of 9 in the IFN group and 3 of 10 in the placebo group were HPV 16 DNA negative (in situ hybridization). All four patients in remission after IFN were HPV 16 DNA negative, whereas 4 of 7 patients in remission after placebo were still HPV 16 DNA positive. One patient treated with placebo showed progression; no patient in the IFN group showed progression. During the post-treatment follow-up of 16 months, no recurrences were noted in the IFN group, as compared with 2 of 10 in the placebo group. These results showed a marked discrepancy between clinical evaluation (colposcopy, Pap smear, biopsy) and virological findings. Further studies are needed to clarify the prognostic value of the different evaluation criteria. It is encouraging that the high-risk HPV 16 infection was eradicated in two-thirds of the patients treated with topical IFN.

Administration, Topical↗
PubMed1990

The correlation between dysmenorrhea and the pain experienced during laser ablation of a cervical lesion.

Twenty women undergoing colposcopically directed laser evaporation of a cervical intraepithelial neoplastic (CIN) lesion were recruited. Using a linear analog scale they scored the pain associated with a normal period when not using contraception. Under standardized conditions and without any analgesia or local anesthesia their transformation zone was ablated to a depth of approximately 6 mm by an independent operator. Pain was assessed 10 min after the procedure by the same technique as that used for the measurement of dysmenorrhea. There is a direct correlation (r = 0.7) between the discomfort of dysmenorrhea and discomfort at colposcopy. This allows the operating colposcopist to predict which patients are most likely to experience discomfort during laser evaporation of a cervical lesion.

Dysmenorrhea↗
PubMed1990

Interferon gamma treatment for cervical intraepithelial neoplasia.

Eight patients with cervical intraepithelial neoplasia (CIN) were administered perilesional injections of human recombinant interferon gamma (IFN-gamma), and the response was evaluated by colposcopy and exfoliative cytology and then by histopathology. In all patients, colposcopic and cytologic findings improved after two to four injections of IFN-gamma and the cytologic findings reverted to normal in five of these eight patients. All five were free of dysplastic lesions. The other three patients with positive cytology and positive colposcopy after completion of IFN-gamma treatment underwent hysterectomy or laser conization, and histopathologic examination revealed residual dysplastic lesions. On the other hand, a control study revealed that only one of eight patients showed spontaneous regression during the 3-month observation period. During the course of these treatments, keratinizing cells were often present in the cervical smears and isolated cell keratinization was often evident in the residual dysplastic lesions of the surgical specimens. These observations suggest that IFN-gamma treatment is an effective therapeutic method for CIN lesions and that IFN-gamma has the potential to differentiate nonkeratinizing squamous cells into keratinizing cells.

Adult↗
PubMed1990

Clinical significance of hyperkeratosis and parakeratosis in otherwise negative Papanicolaou smears.

To ascertain the clinical significance of hyperkeratosis and parakeratosis in otherwise negative Papanicolaou smears, we retrospectively reviewed 96 patients with these findings seen during a 32-month period. Evaluation included repeating the smear and performing colposcopy in all patients. Colposcopically directed biopsy and endocervical curettage were performed when appropriate. Only one patient had human papillomavirus (HPV) infection. The isolated finding of hyperkeratosis or parakeratosis was not associated with an increased incidence of cervical intraepithelial neoplasia or HPV and, clinically, was not associated with uterine descensus or vaginal prolapse.

Adult↗
PubMed1991

Conservative management of cervical intraepithelial neoplasia during pregnancy.

Conservative treatment of a pregnant woman with moderate dysplasia that progressed to microinvasive carcinoma within 6 months is presented along with a review of the relevant literature to date. Pregnancy does not necessarily create special difficulties for the detection and diagnosis of cervical lesions as long as the patient is followed carefully. In this case, close observation using cytology and colposcopy along with colposcopically directed excisional biopsy postponed the need for more aggressive intervention, while minimizing possible disruption of the pregnancy and danger to the mother and infant. A simple hysterectomy performed 6 weeks postpartum proved successful and the cancer has not recurred.

Adult↗
PubMed1992

Diagnostic value of conization of the uterine cervix in the management of cervical neoplasia: a review of 756 consecutive patients.

A review of 584 consecutive cases of conizations performed over a 15-year period showed that 320 patients (54.8%) had conizations because of the presence of neoplastic cells in the endocervical curettings. Of these patients, 268 (83.4%) had cervical intraepithelial neoplasia of various grades on conization, and 12 (3.6%) had microinvasive cancer. The remaining 40 patients had normal cervical epithelium. One hundred seven (18.3%) patients had conization because of cytological smear and colposcopy discrepancy. Seventy-six (71.0%) patients in this category had cervical intraepithelial neoplasia. Two (2.0%) had superficially invasive cancer; the remaining 29 patients had normal cervical histology. Sixty-seven (11.5%) had conizations because of unsatisfactory colposcopic evaluations. This review indicates that although conization is less frequently performed, it is still a useful tool in the management of patients with abnormal cytology in whom colposcopy evaluation cannot rule out invasive cancer.

Adolescent↗
PubMed1992

The prevalence of HPV16DNA in normal and pathological cervical scrapes using the polymerase chain reaction.

Human papillomavirus (HPV) has been implicated in the development of cervical cancer. Newly developed molecular techniques have facilitated HPV identification and typing of cervical lesions. Several studies have suggested a strong correlation between HPV16 and intraepithelial cervical neoplasia. However, there is no agreement on this point since HPV16 is detected also in normal cervical tissue. We have amplified the L1 region of HPV16 DNA using the polymerase chain reaction (PCR) technique and analyzed the HPV16 prevalence in cytological scrapes of 201 Italian sexually active patients. One hundred twenty-four of these women had normal cytologic and colposcopic examination, while seventy-seven women had normal or abnormal cytology and a cervical lesion detectable by colposcopy. Within this latter group, 25 of 77 women (32.4%) were positive for HPV16 DNA, compared to 11 of 124 samples (8.87%) from women with normal cytology and colposcopy. The present results confirm the high efficiency of the PCR technique in detecting HPV16 DNA from cervical scrapes and suggest that this analysis should become a method of choice in clinical studies.

Adult↗
PubMed1991

Screening for cervical cancer by direct inspection.

Since cytology-based screening programmes for cervical cancer cannot be provided on a large scale in developing countries, an alternative approach is needed. To find out whether visual inspection of the cervix is an adequate alternative, women with cytological evidence of dysplasia were followed up cytologically and colposcopically until cancer was detected, and the gross appearance of the cervix was recorded at each stage. Although only 40-50% of cancers were accompanied by abnormal-looking cervices, whereas 71% were detectable on cytology and 87% on colposcopy, visual inspection may be useful in areas where cytological screening programmes are not available.

Adult↗
PubMed1991

Genital abnormalities in female siblings and friends of child victims of sexual abuse.

We evaluated the merit of a directive issued by The Tennessee Department of Human Services (TDHS) requesting a medical evaluation for all children who were closely associated with a victim of sexual assault, even if these children denied being victims themselves. In a 6-month period, 247 girls, age 12 and under, were referred for medical evaluation. Of these, 188 were primary victims of sexual abuse, and 59 girls were secondary victims, associates of victims of abuse. All examinations were performed in an office setting. A colposcope was used to magnify the findings. Of these 59 girls, 45 girls were found to have abnormal genital findings. Nonspecific findings were present in 5 girls (8%), and findings considered specific for sexual abuse were observed in 40 girls (68%). When compared with 5 girls (8%), and findings considered specific for sexual abuse were observed in 40 girls (68%). When compared with primary victims, secondary victims were more likely to demonstrate genital abnormalities suggestive of sexual abuse. (chi 2 = 13.7, p = .0011). Of the 50 secondary victims who were later interviewed by TDHS, 24 girls (48%) reported that they were also victims of assault. We strongly recommend that siblings of sexual abuse victims, as well as other children who are closely associated with them and exposed to the perpetrator, be evaluated to determine whether they have abnormalities suggestive of sexual assault.

Child↗
PubMed1992

Detection of multiple types of human papillomavirus in a giant condyloma from a grafted patient. Analysis by immunohistochemistry, in situ hybridisation, Southern blot and polymerase chain reaction.

Immunosuppressed patients such as transplant recipients are known to develop multiple lesions suggestive of human papillomavirus (HPV) infection. A giant anal condyloma was obtained from a transplant patient; several fragments taken from different areas were examined for the presence of HPV DNA using in situ hybridisation, polymerase chain reaction (PCR) and Southern blot. Typical koilocytes were seen in routinely stained tissue sections, suggesting an HPV infection; furthermore, group specific HPV antigen was detected in one of four frozen fragments. Different results were obtained by in situ hybridisation according to the fragment tested. HPV types 6/11 were detected in each of the five fragments, frozen or fixed in Bouin's or formalin solutions. However, the number of HPV DNA positive cells and the intensity of the reaction greatly varied with the specimen. HPV 16 and 18 probes also reacted positively with the sample fixed in formalin; a stronger signal was observed with HPV 18 in one large focus than with HPV 16. HPV type 5 was detected in a few isolated cells of two frozen fragments. With the Southern blot technique, the profile of an HPV 6/11 was seen only in one of two frozen fragments; in this case, the bands were intense. A slight positive reaction was also obtained in one frozen fragment with HPV 16 probe. Four frozen fragments were analyzed with PCR: HPV 6/11 was detected in each fragment; HPV 18 was detected in the four samples but with different intensities; HPV types 5 and 16 did not show any positive signal. In conclusion, the lesion is an example of infection with several HPV types, demonstrated by three different techniques. This suggests the need for careful dermatological or colposcopic follow-up of transplant recipients, in order to prevent possible malignant transformation of anogenital lesions.

Adolescent↗
PubMed1996

Dilating the cervix medically to overcome an unsatisfactory colposcopy: 5 year follow up.

OBJECTIVE: To examine the long term results of placing a hydroscopic sponge in the cervix to expose high lesions and overcome an unsatisfactory colposcopic examination. STUDY DESIGN: Forty-one women presenting with their first abnormal smear but an unsatisfactory colposcopy were offered medical dilation of the cervix with Lamicel. These women had local ablative treatment and were followed for 5 years to establish the risk of recurrent disease after medical dilation. For comparison we measured the risk of recurrence after a cone biopsy performed as primary treatment for women attending a different hospital in the same city. RESULTS: Medical dilation was unacceptable or failed in 16 of the 41 women. It was initially successful at exposing the entire transformation zone and sparing 25 women a cone biopsy. Ten of these presented with recurrent disease requiring a cone biopsy within 5 years. Two cases were lost to follow up leaving 13 out of a total of 38 women who ultimately avoided a cone biopsy. The recurrent disease rate despite local treatment following medical dilation is 43%. The recurrent disease rate in the city following a cone biopsy is 20%. CONCLUSION: Although medical dilation of the cervix may permit lesions in the canal to be visualised, follow up is difficult and the risk of further disease is high. It is not recommended as a routine.

Biocompatible Materials↗
PubMed1994

Treatment of skin ageing symptoms in perimenopausal females with estrogen compounds. A pilot study.

A wide range of somatic symptoms of the perimenopausal female is due to the decrease of estrogen at that age. Minor attention has been paid hitherto to the involvement of estrogens in female skin ageing symptoms. In our study, the ageing skin of the face of perimenopausal females was treated with a 0.3% estriol cream (8 patients) or with a 0.01% estradiol cream (10 patients) for 6 months. Dermatologic follow-up was performed monthly. At each follow-up venous blood for radioimmuno assay determination of prolactin (PRL), follicle stimulating hormone (FSH) and estradiol (E2) was sampled. In addition, prior to and after 3 and 6 months of treatment, gynecological examinations for climacteric symptoms, mammary and colposcopic investigations and vaginal smears for cytology were performed. Both treatment groups showed improvement of the various skin ageing symptoms at the end of treatment. The effects of the group treated with topical estriol were slightly superior with regard to their extent and onset. No hormonal side effects were noted either clinically or by hormone monitoring. According to these preliminary results, local estrogen treatment appears to be a promising new approach for the treatment of skin ageing in perimenopausal females. However, for minimizing the risk of systemic hormonal side effects, concentrations and size of application field should be limited.

Administration, Cutaneous↗
PubMed1991

Detection of human papillomavirus and human cytomegalovirus in cervical lesions by in situ hybridization using biotinylated probes.

Infections with specific types of human papillomavirus (HPV) have emerged as necessary but not sufficient factors in the development of the majority of cervical cancers. The infection by human cytomegalovirus (HCMV) has also been implicated in both cervical intraepithelial neoplasia (CIN) and cancer. In order to test prevalence of these viral pathogens in genital lesions with suspect cytopathic changes after observation of smears, cervical biopsies from 131 patients were obtained under colposcopic guidance. The biopsies were tested for the presence of HPV and HCMV by the in situ hybridization technique using biotinylated DNA probes on paraffin-embedded sections. Presence of HCMV is twice more frequent in women with HPV-induced cervical lesions (40%) than in women with any detectable HPV (20%). It may be concluded that HCMV might contribute as one synergistic factor in the development of cervical dysplasia.

Cervix Uteri↗
PubMedDate not supplied

Long-term evaluation of the diethylstilbestrol (DES) syndrome in adult female rhesus monkeys (Macaca mulatta).

This study was designed to examine the transplacental effects of diethylstilbestrol (DES) in rhesus monkeys (Macaca mulatta). Nineteen pregnant females received an approximate human therapeutic dose of 1 mg/day DES beginning on gestational day 21 (Group I), day 100 (Group II), or day 130 (Group III) until term. Colposcopic examination and vaginal biopsies were performed in eight female offspring at 6- and 12-month intervals beginning at 3.5 years of age until death between 5 and 12 years of age. Gross and histological evidence of vaginal adenosis was observed in five of eight (62.5%) females. Adenosis, which occurred in all treatment groups, did not develop into neoplasia; rather, it underwent metaplasia and reversion to squamous epithelium, a frequent observation in human DES cases. The vaginal ridging and/or cervical hooding characteristic of the human syndrome was observed in all exposed females. Although menstrual cyclicity was not impaired, there appeared to be a lower pregnancy rate in treated animals compared to age-matched controls. This long-term evaluation of reproductive morphology and function in the rhesus monkey has provided a useful model for studying the history of benign vaginocervical abnormalities induced by prenatal DES treatment.

Abnormalities, Drug-Induced↗
PubMed1994

Detection and identification of human papillomavirus DNA in genital tract by digoxigenin labelling using the polymerase chain reaction method.

We propose here a simple and rapid method of Human Papillomavirus (HPV) detection applied to genital samples. The method consists of a polymerase chain reaction (PCR) of samples using a consensus primer ser (Snijders et al., 1990) with labelling by Dig-dUTP (Digoxigenin deoxyuridine triphosphate) during amplification. Type identification was carried out by hybridization of the labelling PCR product with a panel of different plasmidic HPVs dotted beforehand on nylon membranes. Forty-five genital samples were tested with this method (30 samples with evident signs of HPV infection, and 15 cervical scrapes which had a normal colposcopic examination and no cytologic signs of HPV infection). We found good sensitivity and specificity levels. The labelling method during PCR did not modify the sensitivity of PCR. Forty-five genital samples were analyzed by this technique and compared with the results of dot-blot and two PCR methods using different primers. They showed a good correlation except in four samples (high grade cervical lesions) which seemed to show a partial deletion or rearrangement. Our method, used for the first time in HPV detection, needed just one PCR and one dot-blot, thus saving an important amount of time and also decreasing examination costs.

Journal Article↗
PubMed1993

HLA expression in pre-invasive cervical neoplasia in relation to human papilloma virus infection.

A significant proportion of cervical carcinomas show loss of major histocompatibility complex human leucocyte antigen (HLA) class I expression while upregulating HLA class II expression. These changes may have direct consequences for immune surveillance of the human papilloma virus (HPV) infection which is strongly associated with cervical malignancy. A relationship between changes in HLA expression and HPV infection may be evident in the evolution of premalignant disease. This immunohistological study of 104 colposcopic biopsies establishes that HLA class II expression occurs in a significant proportion of squamous epithelia showing histological evidence of wart virus infection and cervical intraepithelial neoplasia (CIN) I to III. In comparison, alteration of HLA class I expression in cervical premalignant lesions is rare. There is no correlation between the detection of high risk HPV DNA (types 16, 18, 31 and 33) by polymerase chain reaction (PCR) and the MHC class II phenotype of the lesion. This suggests that altered HLA class II expression is neither a consequence nor a prerequisite for HPV infection.

DNA, Viral↗