The use of colposcopy for triage in HPV-positive women aged 65 years and older.

PURPOSE: Persistent high-risk HPV infection is associated with an elevated risk for prevalent CIN II + despite normal cytology (NILM). Our study aims to evaluate the clinical relevance of a persistent high-risk HPV infection without cytologic changes in women aged ≥ 65 and to determine the role of colposcopy for triage in these cases. METHODS: 211 patients aged ≥ 65 with persistent HPV infection and normal cytology (NILM) who presented for colposcopy at five certified centers between January 2021 and April 2022 were included in the study. Colposcopic findings, HPV subtypes, when available, histology and p16/Ki67 staining were assessed as well as individual risk factors such as smoking and previous HPV-related surgery. RESULTS: 87.7% (185/211) of the included women had a type 3 transformation zone. In 83.4% (176/211), a biopsy was taken [thereof 163 endocervical curettages (ECC)]. In 35/211 women (16.6%), sampling was not possible during colposcopy due to an inaccessible cervix, pain during examination or obliteration of the cervical canal. Out of these, 6 women received a diagnostic excision. CIN II + was detected in 10.6% of all histologies (excisional or biopsy) (20/182). 50% of the women with a CIN II + where HPV 16 positive. Taking only the women diagnosed with CIN III or AIS into account, (n = 12) 75% were HPV 16 positive. Interestingly, 80% of the women with CIN II + had an abnormal cytology when repeatedly taken during colposcopy, vice versa an endocervical lesion was diagnosed in 53% of women with abnormal repeat cytology (27/51). CONCLUSION: The prevalence of CIN II + in women is ≥ 65 with persistent hr HPV infection but NILM cytology is similar to that in younger women. However, more than 85% of the women have a type 3 transformation zone. Colposcopy is, therefore, not helpful to diagnose the women who need treatment in this age group.

Prevalence of oral HPV infection in cervical HPV positive women and their sexual partners.

PURPOSE: Human papillomavirus (HPV) infection represents the primary cause of anogenital premalignant and malignant disease. Regarding the high prevalence of cervical HPV infection and the increasing incidence of HPV associated oropharyngeal cancer in recent years, a significant viral transmission from the cervical to the oral site, possibly depending on the sexual behavior must be considered. The present study aims to determine the prevalence of oral HPV infection in cervical HPV positive and negative women and their sexual partners. METHODS: Cervical HPV positive and negative women and their sexual partners took part in the study. Cervical smears, oral smears and mouthwashes were taken from women attending gynecological outpatient clinics in two different institutions. Further, oral smears as well as mouthwashes of their sexual partners were obtained whenever possible. HPV genotyping was performed using the Cobas® polymerase chain reaction and nucleic acid hybridization assay for the detection of 14 high-risk HPV types. In addition, all participants were invited to complete a personal questionnaire. RESULTS: 144 HPV positive and 77 HPV negative women and altogether 157 sexual partners took part in the study. Age, sexual behaviour, medication, smoking and alcohol consumption were distributed equally in both groups. Cervical HPV positive women had a significantly higher number of sexual partners. One woman with a HPV positive cervical smear and one partner of a woman with a HPV positive cervical smear showed an oral HPV infection. No oral HPV infections were detected in the HPV negative control group. The overall incidence of oral HPV infection was 0.5%, the incidence of oral HPV infection in women with a positive cervical smear was 0.7%. CONCLUSION: The data demonstrate that the overall risk of an oral HPV infection is low. HPV transmission to the oropharynx by autoinoculation or oral-genital contact constitute a rare and unlikely event.

Expression of the carbohydrate tumour marker Sialyl Lewis A, Sialyl Lewis X, Lewis Y and Thomsen-Friedenreich antigen in normal squamous epithelium of the uterine cervix, cervical dysplasia and cervical cancer.

The carbohydrate molecules Sialyl Lewis X (SLeX), Sialyl Lewis A (SLeA), Lewis Y (LeY) and Thomsen-Friedenreich antigen (TF) are known to mediate the adhesion between tumor cells and endothelium. They are used as serum markers in diagnosis and treatment in a broad spectrum of human carcinomas, but their expression profile and role in the development of cervical cancer remains unclear. The aim of this study was to investigate the expression of SLeX, SLeA, LeY and TF in normal cervical squamous epithelium, cervical dysplasia and cervical cancer. Slides of paraffin-embedded tissue were fixed and incubated with monoclonal antibodies against SLeX, SLeA, LeY and TF. Immunohistochemical staining was evaluated by using a semi-quantitative score (IRS Score). We found a significant difference of SLeA expression in invasive cervical cancer compared to normal epithelium (p=0.006) and all grades of dysplasia (p=0.002). The expression of SLeX in normal epithelium was less intense than in carcinoma in situ (p=0.036). Staining for LeY showed the weakest results of the investigated markers. Significant differences were found when normal epithelium was compared to CIN I (p=0.011), to CIN II (p=0.013) and to invasive cervical cancer (p=0.005). For TF, significant differences were found in normal epithelium compared to CIN I (p=0.011), CIN II (p=0.013) and compared to invasive cervical cancer (p=0.005). This is the first study on the expression of SLeA, SLeX, LeY and TF in normal cervical endothelium, cervical dysplasia, carcinoma in situ and invasive cervical cancer. Further studies and higher numbers are desirable.

Genital tuberculosis as the cause of tuboovarian abscess in an immunosuppressed patient.

BACKGROUND: Although tuberculosis (TB) is a major health problem worldwide, primary extrapulmonary tuberculosis (EPTB), and in particular female genital tract infection, remains a rare event. CASE REPORT: A 35-year-old human immunodeficiency virus (HIV) seropositive woman of African descent with lower abdominal pain and fever of two days duration underwent surgery due to left adnexal mass suggesting pelvic inflammatory disease. The surgical situs showed a four quadrant peritonitis, consistent with the clinical symptoms of the patient, provoked by a tuboovarian abscess (TOA) on the left side. All routine diagnostic procedures failed to determine the causative organism/pathogen of the infection. Histopathological evaluation identified a necrotic granulomatous salpingitis and specific PCR analysis corroborated Mycobacterium tuberculosis (M. Tb). Consequently, antituberculotic therapy was provided. CONCLUSION: In the differential diagnosis of pelvic inflammatory disease, internal genital tuberculosis should be considered. Moreover, physicians should consider tuberculous infections early in the work-up of patients when immunosuppressive conditions are present.

[Treatment of pregnancy associated gynaecological malignancies]. / Die Therapie gynäkologischer Malignome in der Schwangerschaft.

Pregnancy, leading to new life, on one hand, and life threatening malignancies an the other hand, are per se diametric subjects. Symptoms of malignancies are ignored more frequently during pregnancy by patients and physicians, often resulting in delayed diagnosis. Diagnosis and treatment of gynaecological malignancies, however, are increasingly important for four reasons: the peak incidence of several malignancies occurs during the reproductive age; late pregnancies present more often in an age group with increased risk for cancer, intensified care for pregnant women leads to more thorough diagnosis, and, curative treatment of malignancies gives women the potential chance for becoming pregnant. For these reasons, special features of the diagnosis and treatment of gynaecological malignancies will regularly part of routine patient care. This review article covers certain practice related features of gynaecological malignancies.

Quality of life influenced by primary surgical treatment for stage I-III breast cancer-long-term follow-up of a matched-pair analysis.

BACKGROUND: Breast-conserving therapy has been demonstrated to be just as safe and a less disruptive experience compared with mastectomy for surgically manageable breast cancer. There is, however, no agreement in the literature about the impact of these procedures on several important aspects of quality of life (QOL). The purpose of the present study is to compare the long-term impact of these two surgical approaches on QOL in patients with identical tumor stages and to suggest possible shortcomings of the standard QOL questionnaires. METHOD: Between August 1999 and May 2000, QOL questionnaires were answered by 152 pair-matched patients at the I. Frauenklinik, Ludwig-Maximilians University Munich, as part of routine follow-up examinations. The pairs of patients, each consisting of one patient after mastectomy and one after breast conservation, were selected according to the highest degree of equivalence in tumor stage. All patients had been initially treated for stage I-III breast cancer without evidence of distant metastases. The QOL was evaluated by using the QLQ-C30 questionnaire version 2.0 of the EORTC Study Group on Quality of Life. We formulated seven additional questions about the patients' satisfaction with the primary surgical treatment modality as viewed from their current perspective. The QOL questionnaires were answered after a median interval of 46 months following primary treatment. RESULTS: Tumor stage, prognostic factors, and adjuvant systemic treatment were well balanced between the two groups. No differences between the two groups were observed in terms of all QOL items measured by the QLQ-C30. Our additional questions, however, revealed that patients in the mastectomy group were less satisfied with the cosmetic result of their primary operation (P < .0001), were more likely to feel basic changes in their appearance (P < .0001), and were more likely to be emotionally stressed by these facts (P < .0001). From their perspective at the time of completing the questionnaires, 11 patients in the mastectomy group (15%) would decide differently about the surgical treatment modality, compared with only 3 patients (4%) in the breast conservation group (P = .025). CONCLUSION: While the primary surgical treatment modality seems to have no long-term impact on general QOL, certain body-image-related problems may be caused by mastectomy. Standard measuring instruments for QOL may fail to detect differences in satisfaction and adaptation with the primary surgical treatment modality.

Matched pair analysis of survival after chest-wall recurrence compared to mammary recurrence: a long-term follow up.

BACKGROUND: Local recurrence remains a major concern after primary treatment of breast cancer and has a major impact on subsequent survival. While most studies report a poorer survival rate in patients with a local recurrence after mastectomy than after breast conservation, it remains controversial whether different risk profiles at the time of primary diagnosis may account for this difference. METHOD: Matched pair analysis of 134 patients with newly diagnosed locoregional recurrence of breast cancer without evidence of systemic disease. Matching criteria included the primary surgical treatment, tumor size, nodal status, and age. The significance of various prognostic parameters at the time of primary diagnosis and at the time of recurrence were evaluated, by univariate and multivariate analyses, with respect to survival after recurrence. The median follow-up was 8.4 years. RESULTS: Risk factors at the time of presentation, such as tumor size and lymph node status, were comparable between both groups. Local recurrence occurred on an average 9 months earlier in patients after mastectomy (P = 0.08). Univariate analysis showed that lymph node status (P = 0.0001) and disease-free interval from primary treatment to local recurrence (P = 0.0002) were the most significant single prognostic factors for subsequent survival after local recurrence. The primary surgical treatment modality was shown to be of marginal statistical influence (only P = 0.05). CONCLUSION: Local recurrence after mastectomy seems to be associated with worse survival than after breast-conserving therapy. Early onset of chest-wall recurrence, moreover, represents the highest independent risk for cancer-associated death.

[Prospective randomized study comparing the effectiveness and tolerance of various low-molecular-weight heparins in high risk patients]. / Prospektiv randomisierte Studie zum Vergleich der Wirksamkeit und der Verträglichkeit verschiedener niedermolekularer Heparine bei Hochrisikopatienten.

INTRODUCTION: In several studies, low-molecular-weight-heparins (LMWH) have been shown to be as effective in the prevention of deep vein thrombosis (DVT) as unfractionated heparin. However, different LMWHs vary significantly in their pharmacokinetic profile and bioavailability pattern. It remains unknown, whether these pharmacological differences result in a clinically divergent behavior. METHODS: Safety and antithrombotic efficacy of three LMWHs, certoparin (18 mg), dalteparin (30 mg) and enoxaparin (24 mg), were compared in a prospective, randomized controlled trial involving 188 patients undergoing knee or hip replacement or spinal surgery. Efficacy was assessed by changes in venous flow patterns between pre- and postoperative Doppler sonography. The clinical endpoint for the assessment of safety were intra- and postoperative bleeding, changes in activated partial thromboplastin time (APTT) and thrombin clotting time (TCT), local hematoma and local infections. RESULTS: Two verified DVTs (1.1%) were observed in the study, leading to no statistical difference in the antithrombotic efficacy of the used LMWHs. In 21 patients (11.2%) local hematoma or local infections complicated the postoperative course. Of these 21 patients, 13 belonged to the certoparin group, compared to 4 patients each in the other groups (p < 0.01). An allergic reaction occurred in only one case treated with dalteparin. No differences between the groups were observed in terms of intra- and postoperative bleeding, APTT, TCT and blood count. CONCLUSION: The results of this study suggest, that all three LMWHs are equally efficacious in the prophylaxis of DVT in high risk patients after orthopedic surgery. Larger randomized controlled trials are necessary to confirm this conclusion and to evaluate the clinical relevance of the observed differences in postoperative complications.

[Chemotherapy-associated myelosuppression in gynecological oncology]. / Chemotherapieassoziierte Myelosuppression in der gynäkologischen Onkologie.

INTRODUCTION AND OBJECTIVE: A clinically important myelosuppression due to adjuvant chemotherapy is seen more frequently as dosage is intensified and new drugs are used. The assessment of the cytopenia expected is frequently hampered by a lack of directly comparable data. The aim of this study was to compare - in our own patient population - the chemotherapy-associated myelosuppression of four chemotherapeutic regimens used in gynecological oncology. METHODS: 79 patients with primary breast cancer and 26 patients with epithelial ovarian carcinoma underwent cytostatic treatment, and the associated myelosuppression was evaluated by the determination of cytopenia and the need for supportive therapy. The chemotherapy regimens investigated were CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), 5-fluorouracil 600 mg/m(2), 6xq3w), EC/CMF (epirubicin 90 mg/m(2), cyclophosphamide 600 mg/m(2), 4xq3w, followed by CMF, 3xq3w), DE (docetaxel 75 mg/m(2), epirubicin 90 mg/m(2), 6xq3w) and CC (cyclophosphamide 600 mg/m(2), carboplatin AUC 6, 6xq3w). RESULTS: The EC/CMF and DE regimens were used significantly more frequently for more advanced tumor stages, but there were no differences concerning tumor-dependent prechemotherapeutic myelosuppression. Hemopoiesis was most impaired in the CC group with a mean drop of serum hemoglobin of 1.5 g/dl to the end of the cytostatic treatment; correspondingly, most transfusions of concentrated erythrocytes were needed in this group. The strongest suppression of leukopoiesis was found in the DE group, with a mean drop in leukocyte counts of 6.2 x 10(3)/microliter per cycle; in this group, a mean of 7.6 ready-made syringes with 263 microgram Lenogastrim was used to stimulate leukopoiesis. The severest drop in the mean thrombocyte count, i.e. 171.7 x 10(3)/microliter, was found in the CC group. CONCLUSIONS: The CC regimen impairs thrombo- and erythropoiesis most, whereas the DE regimen causes marked leukopenia. The regimen with the smallest myelosuppression was CMF. No severe cytopenia-associated complications were detected in any of the cases investigated.

Treatment of female urinary incontinence with EMG-controlled biofeedback home training.

The aim of the study was to evaluate the efficacy of pelvic floor training with EMG-controlled home biofeedback in the treatment of stress and mixed incontinence in women. Subjects were recruited from the urodynamic outpatient clinic and performed pelvic muscle training with an EMG-controlled biofeedback device for 20 minutes daily for 6 months. The number of pads used per day, the number of incontinence and urgency episodes, voiding frequency, maximum urethral closure pressure, functional urethral length and pressure/transmission ratio during stress were assessed before and after treatment. Thirty-three patients (13 with stress and 20 with mixed incontinence) completed the study. There was a significant decrease in the number of pads used per day, the number of incontinence and urgency episodes, and the voiding frequency. Twenty-eight patients (85%) reported that they were cured or improved. Urodynamic parameters did not change significantly. It was concluded that home pelvic floor training with EMG-controlled biofeedback is efficient in 85% of patients in alleviating the symptoms of genuine stress and mixed incontinence without causing side effects.