Ulla Hørding

Urinary Incontinence in 45-Year-Old Women: An Epidemiological Survey

In an epidemiological health survey, 515 45-year-old women were interviewed about urological problems, particularly incontinence. A pelvic examination was also conducted on 509 of the women. Twenty-two per cent or 114 women stated that they experienced incontinence, which took the form of stress incontinence in 75%, urge incontinence in 11% and a mixture of the two in 14%. Only 14 women, 3% of all the women interviewed, desired medical treatment for incontinence. In the incontinent women, the pelvic examination significantly more often revealed a cystocele, uterine prolapse or impaired function of the levator muscles. No correlation was found between an enlarged uterus and incontinence. In 211 women with one or more of these findings at the gynaecological examination, the frequency of incontinence was 35%; in 298 women with no pathological findings, the frequency was 15%. The frequency of urinary incontinence was not increased in women with higher parity or in postmenopausal women.

Human papillomaviruses and multifocal genital neoplasia.

In 143 patients with vulvar carcinoma (76 cases) or vulvar intraepithelial neoplasia (VIN III, 67 cases), cervical cancer or cervical intraepithelial neoplasia CIN III lesions developed in 39 patients (27%) at some time during their life. In patients with classic keratinizing squamous cell carcinoma (KSC) of the vulva, cervical neoplasia developed in only one of 51 (2%), whereas the frequency was 10 of 25 (40%) in patients with vulvar carcinoma of the basaloid or warty type and 28 of 67 (42%) in patients with VIN III lesions. The original, paraffin-embedded surgical specimens were examined by polymerase chain reaction and type-specific molecular hybridization for human papillomavirus (HPV) DNA of the types 6, 11, 16, 18, and 33. DNA of the oncogenic types HPV 16 or HPV 33 was found in 4% of the KSCs, in 84% of the basaloid or warty carcinomas, in 90% of VIN III lesions, and in 89% of the cervical lesions. The same HPV type was found in both lesions in 81% of the patients with double primary tumors. The results support the concept that VIN III and a subgroup of vulvar carcinomas are HPV-related lesions, that they are frequently associated with another HPV-related genital primary tumor, and that these multiprimary tumors are secondary to an HPV infection involving the entire genital tract.

Human papillomavirus types 11 and 16 detected in nasopharyngeal carcinomas by the polymerase chain reaction

Most nasopharyngeal carcinomas (NPCs) are of the nonkeratinizing or undifferentiated types, which are consistently associated with Epstein‐Barr virus (EBV). The smaller group of highly differentiated, keratinizing NPCs seems to be only infrequently associated with EBV. In order to examine whether these rare tumors were related to another oncogenic virus, the authors used the polymerase chain reaction to examine paraffin‐embedded sections of 15 keratinizing NPCs for human papillomavirus (HPV) types 6, 11, 16, and 18 genomic sequences. HPV DNA was found in 4 tumors (1 HPV‐11‐positive, and 3 HPV‐16–positive tumors). None of 23 undifferentiated or nonkeratinizing NPCs harbored HPV DNA.

Plasma tetranectin and ovarian neoplasms

Plasma tetranectin was measured in 67 controls, 121 patients with a benign or malignant ovarian tumor, and 24 patients with another benign gynecologic disease to evaluate the predictive value of plasma tetranectin. A significant reduction of plasma tetranectin was found in every malignant tumor type except for mucinous tumors. Further a significant correlation was found between stage of tumors and plasma tetranectin. Depending on the cutoff level the sensitivity for stage 1 cancer ranged from 52 to 71%. In stage 1 + 2 the sensitivity ranged from 58 to 75% and for advanced cancer (stage 3 + 4) from 80 to 95%. The corresponding specificities ranged from 97 to 84%. Plasma tetranectin may be a useful tool for detecting early stages of ovarian cancer.

Human Papilloma Virus Type 11 in a Fatal Case of Esophageal and Bronchial Papillomatosis

We report a case of an apparently healthy 27-year-old man with a fatal course of papillomatosis, originating in the distal part of the esophagus and spreading into the main and intermediate bronchus. Human papillomavirus type 11, usually associated with juvenile laryngeal papillomatosis and genital condyloma acuminatum, was detected in the papillomas. In spite of treatment with CO2-laser evaporation of the papillomas, and with systemic as well as topical interferon, VP-16 and bleomycin, the papillomatosis progressed relentlessly during almost 2 years, and finally caused the death of the patient. We have no explanation for the malignant course of wart virus infection in this young man.

Human papillomavirus type 16 in vulvar carcinoma, vulvar intraepithelial neoplasia, and associated cervical neoplasia.

Vulvar intraepithelial neoplasia (VIN) is becoming more widespread and the patients are becoming still younger. Although progression to invasive vulvar carcinoma is uncommon, local recurrences are frequent and about one-quarter of the patients have multicentric genital disease. The aim of the present study was to search for a possible significant association of human papillomavirus (HPV) infection with vulvar carcinoma, recurrences, and multicentric disease. We used the polymerase chain reaction to examine vulvar and cervical biopsies from 43 patients with vulvar neoplasia for HPV type 16, which is the subtype most often detected in genital malignant or premalignant lesions. HPV 16 DNA sequences were found in 14 of 24 (58%) vulvar squamous carcinomas and in 15 of 19 (79%) VIN lesions. Nine patients (21%) had associated cervical neoplasia and six of these harbored HPV 16 in both lesions. Patients with recurrent intraepithelial neoplasia had a significantly higher incidence of HPV 16-positive lesions. No association was found with regard to the occurrence of multicentric disease or risk of malignant progression.

Human papillomavirus types 16 and 18 in adenocarcinoma of the uterine cervix

Fifty cervical adenocarcinomas and 50 squamous cell carcinomas from age-matched patients were examined for human papillomavirus (HPV) types 16 and 18. The polymerase chain reaction was used to examine formalin-fixed, paraffin-embedded carcinoma tissues for 120 and 113 bp sequences, respectively, of the highly conserved E6/E7 regions of the viral genomes. HPV type 16 was detected more often in squamous cell carcinomas than in adenocarcinomas (60% vs 18%, P less than 0.001). Conversely, HPV type 18 was detected significantly more often in adenocarcinoma tissues (52% vs 12% in squamous cell carcinomas, P less than 0.001). These differences may reflect the fact that different virus receptors exist in cervical cells with different morphologic potential, or they may indicate that the specific HPV infection actually plays a role in directing carcinogenesis.

Immunoreactive inhibin-production in post-menopausal women with malignant epithelial ovarian tumors

In post-menopausal women with a malignant epithelial ovarian tumor the follicle stimulating hormone (FSH) level was found to be significantly lower compared with healthy controls. We demonstrated immunoreactive (i.r.) inhibin in 20% of controls which was elevated to 60% of women with an ovarian tumor and correlating strongly to FSH in the tumor group (P = 0.0002). Steroid hormone levels were comparable in the two groups. In women with ovarian tumors the survival time for the i.r. inhibin-producing women was found to be 4.6 years compared with 0.9 year, or 5.1 times longer than in the non-producing women (P = 0.002). The site of i.r. inhibin production in these post-menopausal women is unknown, but i.r. inhibin production by the developing ovarian tumor or by the post-menopausal ovary may be regarded as a defense mechanism against an elevated gonadotrophin level (the gonadotrophin theory) which would promote further tumor growth. The recent suggestion that the alpha subunit of inhibin is a tumor suppressor gene is consistent with these results. The serum i.r. inhibin or alpha subunit concentrations might be used as an aid to diagnosis or as a prognostic indicator of survival in women with an ovarian carcinoma.

Nasopharyngeal carcinoma: Histopathological types and association with Epstein-Barr virus

The polymerase chain reaction was used to examine paraffin-embedded tissues of 37 nasopharyngeal carcinomas (NPC) for Epstein-Barr virus (EBV) genomic sequences. EBV DNA was found in 2/14 keratinising squamous cell (WHO 1) carcinomas and in all of 23 non-keratinising and undifferentiated (WHO 2 and 3) NPC. The study confirms the infrequent association of keratinising NPC and EBV, in contrast with the 100% association of the less differentiated NPCs and the virus. The results may indicate a different carcinogenesis for the WHO 1 NPC subtype.

Epstein-Barr virus and Hodgkin's disease: a comparative immunological, in situ hybridization, and polymerase chain reaction study.

During recent years numerous studies have demonstrated the presence of Epstein‐Barr virus (EBV) in tissues affected by Hodgkins disease (HD). The percentage of cases with evidence of EBV infection has varied among the different studies, a positive result being highly dependent on the sensitivity of the method employed. In this study three different methods of detecting EBV in 48 cases of ‘classical’ HD (33 cases of nodular sclerosis and 15 cases of mixed cellularity) were compared: Immunohistochemistry (IH) for detection of latent membrane protein‐1 (LMP‐1), in situ hybridization (ISH) for detection of Epstein‐Barr virus early RNAs (EBER 1 and 2), and polymerase chain reaction (PCR) for detection of a reiterated 110 base‐pair EBV genomic sequence of the BamHI region. In 14 cases (29%) Hodgkins (H) and Reed‐Sternberg (RS) cells were positive for LMP‐1 using IH, and in 21 cases (44%) positive signals were seen in H‐RS cells with EBER 1 and 2 probes using ISH. A few EBER‐positive non‐malignant lymphocytes were seen in 17 cases. Thirty‐two cases (71%) were EBV‐positive by PCR. It is concluded that the PCR technique is the most sensitive method for detecting EBV in HD. However, this method cannot provide information about the cellular localization of EBV. ISH with EBER 1 and 2 probes is superior to immunohistochemical detection of LMP‐1 with regard to sensitivity. The advantage that the latter two methods have over the PCR techniques is that it is possible to analyse whether the EBV infection occurs in the H‐RS cells or in the admixed non‐malignant cell population. Furthermore, this study supports the observation that EBV is associated with a considerable number of HD cases.