European consensus statement on expert colposcopy.

BACKGROUND: Following the publication of the European consensus statement on standards for essential colposcopy in 2020, the need for standards relating to more complex and challenging colposcopy practice was recognised. These standards relate to colposcopy undertaken in patients identified through cervical screening and tertiary referrals from colposcopists who undertake standard colposcopy only. This set of recommendations provides a review of the current literature and agreement on care for recognised complex cases. With good uptake of human papillomavirus (HPV) immunisation, we anticipate a marked reduction in cervical disease over the next decade. Still, the expert colposcopist will continue to be vital in managing complex cases, including previous cervical intraepithelial neoplasia (CIN)/complex screening histories and multi-zonal disease. AIMS: To provide expert guidance on complex colposcopy cases through published evidence and expert consensus. MATERIAL & METHODS: Members of the EFC and ESGO formed a working group to identify topics considered to be the remit of the expert rather than the standard colposcopy service. These were presented at the EFC satellite meeting, Helsinki 2021, for broader discussion and finalisation of the topics. RESULTS & DISCUSSION: The agreed standards included colposcopy in pregnancy and post-menopause, investigation and management of glandular abnormalities, persistent high-risk HPV+ with normal/low-grade cytology, colposcopy management of type 3 transformation zones (TZ), high-grade cytology and normal colposcopy, colposcopy adjuncts, follow-up after treatment with CIN next to TZ margins and follow-up after treatment with CIN with persistent HPV+, and more. These standards are under review to create a final paper of consensus standards for dissemination to all EFC and ESGO members.

European consensus statement on essential colposcopy.

This European consensus statement on essential colposcopy provides standards for the general colposcopist seeing women referred for colposcopy with an abnormal cervical screening test (including cytology and HPV tests) or with a clinically suspicious cervix. The article gives guidance regarding the aims and conduct of colposcopy. Recommendations are provided on colposcopy technique, the management of common colposcopy issues, treatment and follow-up of after treatment of CIN or early stage cervical. Colposcopists should make an informed decision on the management of each individual that is referred and organize appropriate follow-up. Cervical cancer is still a major health issue and the quality of care can only improve if there is a structured guidance for women with an abnormal smear or suspicious cervix.

Explanation and Use of the Rio 2011 Colposcopy Nomenclature of the IFCPC (International Federation for Cervical Pathology and Colposcopy): Comments on the general colposcopic assessment of the uterine cervix: adequate/inadequate; squamocolumnar junction; transformation zone.

In July 2012 the IFCPC adopted a revised terminology for colposcopic examinations of the uterine cervix. In 2012, the Boards of the Arbeitsgemeinschaft Kolposkopie (AGK - Austrian Society of Colposcopy), the Arbeitsgemeinschaft für Kolposkopie und Zervixpathologie (AGKOL - Swiss Society of Colposcopy and Cervical Pathology) and the Arbeitsgemeinschaft für Kolposkopie und Zervixpathologie (AGCPC - German Society of Colposcopy and Cervical Pathology) accepted the validity of the 2011 IFCPC nomenclature and recommended its use in general clinical practice across German-speaking countries. The revised nomenclature was devised so that examiners can evaluate colposcopic criteria according to a specific scheme. At the start of the examination, the examiner must assess whether the colposcopy is representative or not. 1. Can the examination be classed as adequate or inadequate (reasons must be given)? 2. How would you describe the visibility of the squamocolumnar junction and categorize the transformation zone? Below we discuss some aspects of this general assessment as outlined in the nomenclature which were found to require further clarification for general practice.

Explanation and Use of the Colposcopy Terminology of the IFCPC (International Federation for Cervical Pathology and Colposcopy) Rio 2011.

In July 2012 a revised terminology on colposcopic examinations of the cervix uteri was adopted by IFCPC. Central aspect is a description of characteristics that should aid in the definition of the disease entity cervix uteri. The nomenclature is built up in such a way that the examiner can evaluate colposcopic criteria according to a specific scheme. Firstly it is assessed whether the colposcopy is representative. Then it should be clarified whether or not the findings are normal. If the findings are not normal but rather abnormal the severity of the lesion is classified according to the so-called grade 1 (minor change) and grade 2 findings (major change). Specific abnormal findings such as leukoplakia, erosion and Lugol's finding are also not defined at this point. Characteristics suspicious for an invasion are described separately, in particular, atypical vessel patterns are mentioned here. As already held in the previous revised nomenclature (Barcelona), various findings are described in a last group: congenital transformation zones (CTZ), congenital anomalies, condylomas (papillomas), endometriosis, polyps (ectocervical, endocervical), inflammation, stenosis, postoperative changes (scarred portio, vaginal stump).

What does a young girl experience in her first gynecological examination? Study on the relationship between anxiety and pain.

STUDY OBJECTIVE: The purpose of the two-part study was to determine how the initial gynecological examination was experienced, examining the relationship between anxiety and pain. DESIGN AND PARTICIPANTS: A total of 669 patients who had attended the special gynecological outpatient clinic for female children and adolescents, and 800 female pupils of either high schools (H) or vocational schools (V), were retrospectively asked to complete a standardized questionnaire (30 questions). The statistical instruments used were Chi-square test, loglinear models, and Spearman correlation coefficients. RESULTS: A total of 169 completed questionnaires could be evaluated in the case of children who attended the special outpatient clinic and 210 in the case of the pupils. (1) There was a significantly positive correlation between anxiety and pain; however, the sex of the examiner had no influence on how the examination was experienced. The accompanying persons underestimated the anxiety of the patients prior to the examination and overestimated the pain experienced. (2) Loglinear models showed that there is no relationship between the type of school attended and the pain score, a significant relationship between the type of school and the anxiety (P <.01), and a significant relationship between the anxiety and pain score irrespective of the type of school attended. CONCLUSIONS: The studies showed a surprisingly high frequency of pain, anxiety, and their correlation during the initial gynecological examination. Further studies of influencing factors and interventions are needed.

[Chronic pelvic pain and chronic vulvodynia as multifactorial psychosomatic disease syndromes: results of a psychometric and clinical study taking into account musculoskeletal diseases]. / Chronische Unterbauchschmerzen und chronische Vulvodynie als multifaktorielle psychosomatische Krankheitsbilder: Ergebnisse einer psychometrischen und klinischen Studie unter besonderer Berücksichtigung der muskuloskeletalen Erkrankungen.

OBJECTIVE: Chronic Pelvic Pain Syndrome (CPPS) and vulvodynia (CVPS) are two gynecological syndromes with psychosomatic implications. The purpose of the study was to examine multifactorial psychosomatic syndromes taking into account musculoskeletal diseases. PATIENTS AND METHODS: The psychosomatic data acquired in respect of 106 CPPS and 36 CVPS patients was evaluated. In addition, these patients were subject to orthopedic clinical examinations and the results compared with a control group without pain (n = 35). 68 CPPS and 24 CVPS patients took part in psychological tests, the results of which were compared with those of a control group of healthy women (n = 34). RESULTS: There was a significantly higher incidence of sexual abuse among the CPPS group. Sexual abuse and somatization were found to be significantly predictive factors. The CPPS and CVPS patients were significantly more depressive than the healthy group. The two clinical groups differ in that the CPP syndrome is significantly more frequently linked with a so-called early disturbance. The incidence of musculoskeletal diseases was higher in the case of the CPPS patients. CONCLUSIONS: Interdisciplinary psychosomatic treatment, which also includes nongynecological disorders, especially musculoskeletal diseases, is necessary in the case of both these syndromes.

Chronic pelvic pain syndrome (CPPS) and chronic vulvar pain syndrome (CVPS): evaluation of psychosomatic aspects.

The purpose of our study was to examine the chronic pelvic pain syndrome (CPPS) and the chronic vulvar pain syndrome (CVPS) as two psychosomatic gynecological syndromes. Sociodemographic data were collected from 106 CPPS and 36 CVPS in-patients (under internal and external supervision). Sixty-eight CPPS and 24 CVPS patients were examined using psychological tests (Freiburg Personality Inventory (FBI) and Giessen Test (GT)) and compared with a control group of 34 healthy women. Descriptive statistics, the chi-square test, multi-variant analyses, and regression analyses were used for statistical evaluation. There was a significantly higher incidence of sexual abuse and severe psychological disturbances in the CPPS group (p < 0.03). Sexual abuse was found to be a significant predictor of the CPP syndrome. The CPPS and CVPS patients were significantly more depressed than the control group (p < 0.03). CPPS and CVPS are two distinct psychosomatic gynecological syndromes accompanied by different psychological disturbances.

Psychosomatic aspects of vulvodynia. Comparison with the chronic pelvic pain syndrome.

OBJECTIVE: To examine psychosomatic aspects of vulvodynia (VD) in comparison with the chronic pelvic pain syndrome (CPPS). STUDY DESIGN: Sixty-seven VD patients and 97 CPPS patients were examined with psychological tests (Freiburg Personality Inventory, Giessen Test) and compared with a control group of 34 healthy women. Sociodemographic data and psychoanalytic diagnoses were collected for 36 VD patients and 106 CPPS patients (inpatients). Descriptive statistics, chi 2 test and multivariant analyses were used. RESULTS: CPPS patients had significantly higher somatization than VD patients (P < .004). Both CPPS and VD patients, as inpatients, were significantly more depressive than the control group. In milder forms of VD, the patients (outpatients) exhibited no depression. The incidences of sexual abuse and severe psychological disturbances were significantly higher in the CPPS group (P < .01). CONCLUSION: VD and CPPS are two, distinct psychosomatic gynecologic syndromes and indicate psychosomatically oriented therapy.

[Diagnostic and therapeutic concepts of HPV infection in HIV-positive women]. / Diagnostische und therapeutische Konzepte bei HPV-Infektion HIV-positiver Frauen.

Among HIV-seropositive women there is a high prevalence of anogenital human papillomavirus (HPV) infection. HPV-DNA is more frequent detected in cervicovaginal-lavage specimens from HIV-seropositive women as in those from HIV-seronegative women. We and others suggest that HIV-infection increases the risk to have HPV-associated lesions of the lower female genital tract, especially the risk for developing a squamous intraepithelial lesion of the cervix. In this report we describe the current diagnostic and therapeutic strategies in HIV-seropositive women with HPV-infection. The gynecological examination should be performed at six to twelve month intervals, including the colposcopy and the Pap smear test. We hope to improve the quality of our screening program by doing an additional HPV-test. At last we investigate the CD4+ T-lymphocyte counts because it is observed that women with low CD4+ cell counts (< 200/microliter) were more likely to have persistent HPV-infection as those with higher counts (> 500/microliter). The treatment method is dependent on the development of the HPV-associated lesion and the clinical status of the HIV infected women. In cases with external warts local application of Condylox should be the first line treatment. Probably in about few months we could use other drugs like Wartec or Aldara in Germany. But the effectiveness of these drugs in HIV-positive women has to be proven yet. In the cause of persistence of external warts or recurrence of the disease the systemical application of Intron A or Roferon A is possible. The CO2-lasertreatment is performed under colposcopic guidance, especially in cases with multicentric condylomatous lesions. The treatment of cervical intraepithelial neoplasia (CIN) by CO2-laservaporisation or Loop Electrosurgical Excision Procedure (LEEP) is based on the clear colposcopic visualisation of the upper limit of the lesion. If CIN reaches the endocervix, being out of colposcopic view, and the squamocolumnar junction is localised in the endocervical canal conisation by laser or cold knife has to be performed. Before performing the treatment of CIN one should exclude multicentric cervical, vaginal and vulval intraepithelial neoplasia by colposcopy, because multicentric intraepithelial neoplasia of the lower female genital tract is more frequently than in HIV-seronegative women. Multicentric disease seems to be one cause of the high recurrence of HIV-seropositive women. However, higher levels of immunosuppression (CD4+ T-lymphocyte counts < 200/microliter) are also important determinants of recurrence of the disease. Therefore, an accurate short-term follow-up with colposcopy, Pap test and HPV test should be carried out after the treatment of HIV-seropositive women with low CD4+ counts.

[Pattern of various cytokeratins of normal vulva, vulvar intraepithelial neoplasia (VIN) and vulvar carcinoma]. / Muster verschiedener Zytokeratine der normalen Vulva, der vulvären intraepithelialen Neoplasia (VIN) und des Vulvakarzinoms.

The presence of specific keratins can be of diagnostic value for studying normal and neoplastic epithelium of the vulva. The aim of the present study was to investigate normal, preneoplastic and neoplastic epithelium of the vulva. Keratins 5, 6 and 18, identified by a polyspecific anti-human CK antibody (clone LP 34, DAKO), and the keratin subtypes 7, 10, 14, 18, 19 and 20 of normal, dysplastic and malignant vulval epithelium (paraffin-embedded sections) were detected by immunohistochemical APAAP staining. Keratins 5, 6, and 18 (clone LP 34) and keratin subtype 10 are expressed in the upper third of the normal vulval epithelium. In mild and moderate intraepithelial neoplasia only a few cells express these keratins. In patients with severe intraepithelial neoplasia (VIN III) the expression of these keratins seems to be associated with recurrence of the disease. In biopsy specimens of patients without recurrence we find positive results for keratins 5, 6 and 18 (clone LP 34) and keratin 10. If patients have a recurrence of the disease, expression of these keratins is only diffuse or is absent. The expression of these keratin subtypes in vulval carcinomas is mostly seen in differentiated cells. There was no association between recurrence and keratin pattern. We have not found any other expression of the tested keratin subtypes in VIN and in vulval carcinoma.

Products of the Major Histocompatibility Complex and CD4/CD8 Cell Infiltration in Cervical Intraepithelial Neoplasia and in Cervical Carcinoma.

OBJECTIVES: Major histocompatibility complex (MHC) products and the CD4/CD8 cell ratio in the lymphocyte infiltrate in cervical preneoplastic and neoplastic lesions are investigated to determine the correlation between the infiltration of lymphocytes in subepithelial stromal tissue and the expression of MHC class I and MHC class II antigens on epithelial cells. MATERIALS AND METHODS: The expression of MHC products and the lymphocyte infiltration were studied by an indirect immunohistochemical staining (alkaline phosphataseanti-alkaline phosphatase) in 6 biopsies of normal cervical squamous epithelium, in 22 biopsies of cervical intraepithelial neoplasia (CIN), and in 9 biopsies of cervical carcinoma. Immunohistochemically positive lymphocytes were counted in highpower fields. The density of MHC expression in CIN and cervical carcinoma was described semiquantitatively in the histological slides. RESULTS: We have seen a number of differences in the expression of MHC products between normal cervical squamous epithelium and CIN or cervical carcinoma. Our results also show that the CD4/CD8 cell ratio in normal, in dysplastic, and in malignant cervical tissues differs from peripheral blood. We found statistically significant differences (Mann Whitney U test, p < .05) between the CD4/CD8 ratio of the normal epithelium when compared to the preneoplastic and neoplastic cervical lesions. In the histological sections tested, CD8 cells exceeded the number of CD4 cells in CIN and cervical carcinoma. Expression of MHC products is independent of the infiltration of CD4 and CD8 cells in the tissue of low-grade and high-grade cervical squamous intraepithelial lesions (SILs) and in cervical carcinoma. CONCLUSIONS: We found a significant decrease of the CD4/CD8 cell ratio in low-grade SILs, high-grade SILs, and squamous cell carcinoma compared to normal cervical epithelium. The loss of MHC class I antigen expression in poorly differentiated tumor cells does not correlate with the amount of lymphocyte infiltration.

Risk factors for recurrent VIN. Role of multifocality and grade of disease.

OBJECTIVE: To evaluate possible risk factors for recurrence of vulvar intraepithelial neoplasia (VIN): menopausal status, smoking, method of treatment (local excision with cold knife, CO2 laser vaporization, CO2 laser excision), grade and focality. STUDY DESIGN: At the dysplasia clinic of the Department of Obstetrics and Gynecology, Medical Center, Heinrich Heine University, Dusseldorf, Germany, we treated 102 patients with VIN with a mean follow-up of 3.5 years. VIN was demonstrated for all these patients by histologic examination of biopsies taken under colposcopic control. Follow-up was performed by clinical examination and colposcopy. Statistical evaluation was done by the chi 2 test. RESULTS: VIN recurrence developed in 36.6% of patients. We could not prove any correlation between recurrence of disease and menopausal status, smoking behavior or treatment method used. Recurrent VIN correlated with the grade (P < .001) and focality (P < .05) of the disease. CONCLUSION: In the prediction of possible risk of recurrence of disease, not only the grade of VIN but also the multifocality is important. Treatment should be done very carefully considering the functions of the vulva; therefore, mutilating operations ought to be avoided as much as possible.

Detection of sequential genetic alterations relevant for breast cancer development.

Breast cancer emerges as a multistep process with transformation of normal cells via steps of hyperplasia, premalignant change and in situ carcinoma. Cytogenetic and molecular genetic analyses of breast cancer samples indicate that tumour development involves the accumulation of various genetic alterations, including amplification of oncogenes and mutation or loss of tumour suppressor genes. Microdissection of histological sections is needed to correlate the specific histological change and the genetic alteration. For detection of oncogene amplification quantitative differential polymerase chain reaction (PCR) can be used. For assessment of loss of heterozygosity PCR-based microsatellite polymorphisms detecting differences in short tandem repeat sequences are much more informative than standard two-allele restriction fragment length polymorphism markers. Still, the direct correlation of the genetic alterations to specific histological findings is the key to reveal insight into tumour biology and thereby gain prognostic information for the individual breast cancer patient.

[Therapy of preinvasive vulvar neoplasia--standardized or individual?]. / Therapie bei präinvasiver Vulvaneoplasie--standardisiert oder individuell?

The mostly diagnosed preinvasive vulvar neoplasia is of squamous origin called "vulvar intraepithelial neoplasia" (VIN). The knowledge about the biological character of these lesions especially grade 3 is limited. Progression to invasive cancer is expected in > 40 % of untreated patients who are mostly immunocompromised or elderly. After surgical treatment of VIN the risk of invasive cancer is about 4 %. There are no significant differences in later progression and relapse rates between different surgical approaches. Risk factors for relapse are: younger age, positive margins, grade 3, multicentricity, associated intraepithelial neoplasias of the vagina and uterine cervix and immunosuppression. The aim of treatment is the removal of all lesions with negative margins. Individually adapted surgical excision is mandatory to conserve the function and figure of the vulva. Standard surgical procedures are wide local excision or laser vaporisation after safe histological characterisation.

[Treatment and after-care of HIV patients with cervix dysplasia]. / Behandlung und Nachsorge von HIV-Patientinnen mit einer Zervixdysplasie.

We have been observing an increased prevalence of cervical intraepithelial neoplasia in HIV-infected women in our department of obstetrics and gynaecology. 10 HIV-infected patients with cervical intraepithelial neoplasia were treated by CO2-laser - 6 were subjected to laser excision conisation, and 4 patients to laser vaporisation. After laser vaporisation and laser excision conisation, no postoperative complications were observed. Intraoperative bleeding was rarely seen. The preoperative examination of the CD4-cell count had no influence on the choice of the applied method of laser treatment, laser vaporisation or laser excision conisation. But all the 4 patients with a CD4-cell count < or = 200/microliters experienced recurrence of disease shortly after the first laser treatment. Only one out of five patients with CD4-cell counts between 200-499/microliters had a recurrence of disease after laser treatment. All in all, a recurrence of disease was seen in five out of ten HIV-infected patients with cervical intraepithelial neoplasia. The recurrence rate is possibly increased because HIV-infected women have multifocal cervical, vulval and vaginal dysplasia more frequently than HIV-negative patients. In our study, we observed multifocal cervical, vulval and vaginal dysplasia in four HIV-infected patients. Therefore, an accurate short-term follow-up with colposcopy and cytological smears should be carried out after the treatment of HIV-infected patients with cervical intraepithelial neoplasia.

[The advantages of CO2 laser use in treatment of cervix dysplasia]. / Die Vorzüge der CO2-Laseranwendung bei der Behandlung der Zervixdysplasie.

We use two kinds of laser treatment, namely, laser vaporisation and laser excision conisation. Laser vaporisation is a widely used method of localised ablative treatment based on both histologically confirmed cervical intraepithelial neoplasia and clear colposcopic visualisation of the upper limit of the lesion. Laser excision conisation is performed, if cervical intraepithelial neoplasia reaches the endocervix, being out of colposcopic view, and the squamocolumnar junction is localised in the endocervical canal. 116 patients with cervical intraepithelial neoplasia were treated with the CO2 laser. 81 (70%) were subjected to laser vaporisation, 35 (30%) to laser excision conisation. Intraoperative bleeding was rarely seen. After laser vaporisation, no complications were observed, but laser excision conisation complications occurred in one patient who developed postoperative cervical stenosis, and in another patient, who had postoperative bleeding requiring surgical examination. Follow-up with colposcopy and cytologic smears was carried out every 6 months. Recurrence of disease 6 months or later after laser treatment was seen in 6 patients (7.4%) after laser vaporisation and in 2 patients (5.7%) after laser excision conisation. This report shows the advantages of the carbon dioxide laser in comparison to cold knife conisation in the treatment of cervical intraepithelial neoplasia.