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.

Pelvic lymphadenectomy in vulvar cancer and its impact on prognosis and outcome.

BACKGROUND: The value of pelvic lymphadenectomy (LAE) has been subject of discussions since the 1980s. This is mainly due to the fact that the relation between lymph node involvement of the groin and pelvis is poorly understood and therewith the need for pelvic treatment in general. PATIENTS AND METHODS: N = 514 patients with primary vulvar squamous cell cancer (VSCC) FIGO stage ≥ IB were treated at the University Medical Center Hamburg-Eppendorf between 1996 and 2018. In this analysis, patients with pelvic LAE (n = 21) were analyzed with regard to prognosis and the relation of groin and pelvic lymph node involvement. RESULTS: The majority had T1b/T2 tumors (n = 15, 78.9%) with a median diameter of 40 mm (11-110 mm). 17/21 patients showed positive inguinal nodes. Pelvic nodal involvement without groin metastases was not observed. 6/17 node-positive patients with positive groin nodes also had pelvic nodal metastases (35.3%; median number of affected pelvic nodes 2.5 (1-8)). These 6 patients were highly node positive with median 4.5 (2-9) affected groin nodes. With regard to the metastatic spread between groins and pelvis, no contralateral spread was observed. Five recurrences were observed after a median follow-up of 33.5 months. No pelvic recurrences were observed in the pelvic nodal positive group. Patients with pelvic metastasis at first diagnosis had a median progression-free survival of only 9.9 months and overall-survival of 31.1 months. CONCLUSION: A relevant risk for pelvic nodal involvement only seems to be present in highly node-positive disease, therefore pelvic staging (and radiotherapy) is probably unnecessary in the majority of patients with node-positive VSCC.

Surgical staging and prognosis in serous borderline ovarian tumours (BOT): a subanalysis of the AGO ROBOT study.

BACKGROUND: Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. METHODS: Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). RESULTS: For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66-2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06-3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22-4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15-3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. CONCLUSION: Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed.

Age-dependent differences in borderline ovarian tumours (BOT) regarding clinical characteristics and outcome: results from a sub-analysis of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) ROBOT study.

BACKGROUND: Approximately one-third of all borderline ovarian tumours (BOT) are diagnosed in patients with child-bearing potential. Detailed information regarding their specific characteristics and prognostic factors is limited. METHODS: Clinical parameters of BOT patients treated between 1998 and 2008 in 24 German centres were retrospectively investigated. Central pathology review and prospective follow-up were carried out. Patients <40 versus ≥40 years were analysed separately and then compared regarding clinico-pathological variables and prognosis. RESULTS: A total of 950 BOT patients with a median age of 49.1 (14.1-91.5) years were analysed [280 patients <40 years (29.5%), 670 patients ≥40 years (70.5%)]. Fertility-preserving surgery was carried out in 53.2% (149 of 280) of patients <40 years with preservation of the primarily affected ovary in 32 of these 149 cases (21.5%). Recurrence was significantly more frequent in patients <40 years (19.0% versus 10.1% 5-year recurrence rate, P < 0.001), usually in ovarian tissue, whereas disease-specific overall survival did not differ between the subgroups. In case of recurrent disease, malignant transformation was less frequent in younger than in older patients (12.0% versus 66.7%, P < 0.001), mostly presenting as invasive peritoneal carcinomatosis. Multivariate analysis for patients <40 years identified advanced International Federation of Gynecology and Obstetrics (FIGO) stage and fertility-sparing approach as independent prognostic factors negatively affecting progression-free survival (PFS) while, for patients ≥40 years, higher FIGO stage and incomplete staging was associated with impaired PFS. CONCLUSIONS: Despite favourable survival, young BOT patients with child-bearing potential are at higher risk for disease recurrence. However, relapses usually remain BOT in the preserved ovaries as opposed to older patients being at higher risk for malignant transformation in peritoneal or distant localisation. Therefore, fertility-sparing approach can be justified for younger patients after thorough consultation.

Health-related quality of life and patient-defined benefit of clobetasol 0.05% in women with chronic lichen sclerosus of the vulva.

BACKGROUND: This study investigates the health-related quality of life in patients with vulvar lichen sclerosus (LS) and the patient-defined therapeutic benefit of clobetasol. METHODS: A survey analysis of 96 women with LS after treatment with clobetasol was performed. Quality of life was assessed with the Skindex-29. The Patient Benefit Index (PBI) was used to determine the therapeutic benefit. RESULTS: The overall response rate was 59.2%. Quality of life was most impaired by somatic symptoms (scale 'Symptoms' score 3.2) and emotional stress (scale 'Emotions' score 3.1), while social interactions (scale 'Functioning' score 1.9) played an inferior role (p < 0.001). Primary therapeutic goals 'to have confidence in the therapy' and 'to be free of itching' were achieved in 73.2 and 69.0% of patients who indicated the goal applied to them. The global PBI score was 3.06. In 93.2% of patients it was >1, indicating a potential benefit from clobetasol. CONCLUSION: Topical clobetasol is of potential therapeutic benefit for patients with vulvar LS and might therefore improve quality of life.

EGFR gene copy number increase in vulvar carcinomas is linked with poor clinical outcome.

EGFR copy number increases have been frequently reported in cancer including vulvar carcinomas. Co-amplification of cancer genes plays an important role in the development of many tumour types. To better understand the effect of EGFR aberrations on vulvar cancer phenotype and patient prognosis, the authors analysed EGFR copy number changes using fluorescence in situ hybridisation and EGFR expression by immunohistochemistry in a tissue microarray containing 183 squamous cell carcinomas of vulva. Furthermore, the authors analysed the co-amplification frequency of EGFR with HER2, CCND1, MYC and PIK3CA, respectively. EGFR copy number increase was found in 39.3% of the tumours. Seventeen per cent of vulvar carcinomas showed EGFR high polysomy including 9% with amplification of the EGFR gene. Copy number gain of the EGFR locus was associated with non-basaloid phenotype (p=0.03), high-tumour stage (p<0.001), human papillomaviruse negativity of tumours (p=0.04) and the number of lymph node metastases (p=0.02). EGFR protein expression was statistically correlated to EGFR copy number increase (p<0.05). The observed co-amplification rate of EGFR with all four additionally examined oncogenes was much higher than statistically expected. There was a highly significant association between EGFR copy number increase and CCND1 amplifications (p<0.001) as well as the total number of gene amplifications (p=0.04). EGFR copy number gains were significantly related to unfavourable patient outcome in univariate analysis and multivariate Cox regression analysis. In conclusion, EGFR copy number increases are detectable in a substantial proportion of vulvar carcinomas with relationships to advanced tumour stages and the development of lymph node metastases. EGFR copy number aberrations are connected to other gene amplifications and probably define an human papillomaviruses-independent pathway in the development of vulvar carcinomas. These data support the potential utility of EGFR inhibitors as a therapeutic alternative in a subset of vulvar carcinomas.

BIRC2 amplification in squamous cell carcinomas of the uterine cervix.

Oncogene amplification is a key step in cell transformation towards malignancy. Chromosomal aberrations involving the long arm of chromosome 11, including amplifications at 11q13 and 11q22, have been previously reported in cervical cancer. While the role of the CCND1 gene as the driver gene for 11q13 amplification is well established in different tumor types, the significance of the 11q22 amplicon is less clear. The 11q22 amplicon corresponds to several putative target genes including the apoptose inhibitor BIRC2, recently detected as amplified in cervical cancer cell lines. To better understand the distribution and frequency of 11q amplification sites in uterine cervical carcinomas, we analyzed BIRC2 and CCND1 copy number changes using fluorescence in situ hybridization in a tissue microarray containing 238 cervical cancers. High-level amplification of BIRC2 was found in 12.9 % of tumors. Amplification of BIRC2 in cervical carcinomas was homogeneous as shown in corresponding whole tissue sections of amplified tumors at the tissue microarray. BIRC2 amplification was significantly more frequent than CCND1 amplification (2.1 %) in our cohort (p < 0.01), and amplification of both genes were independent from each other. BIRC2 amplification was associated with younger-patient age (p < 0.05) and squamous cell differentiation (p = 0.025) of cervix carcinomas. However, BIRC2 copy number changes were not related to tumor stage, grading and nodal status of cervical cancers. In conclusion, BIRC2 is amplified in a subset of squamous cell carcinoma of the uterine cervix. Further studies are necessary to evaluate possible prognostic effects of BIRC2 copy number gains in cervical carcinomas.

Perioperative morbidity and outcome of secondary cytoreduction for recurrent epithelial ovarian cancer.

BACKGROUND: Despite radical surgical and chemotherapeutic treatment of ovarian cancer, the majority of patients develop recurrent disease. Secondary cytoreductive surgery can result in favourable outcome in selected patients, but information regarding feasibility, safety and perioperative outcome of these often complex procedures is limited. METHODS: Surgical parameters in patients with recurrent epithelial ovarian cancer selected for secondary cytoreduction were analysed and compared to patients undergoing primary cytoreduction. RESULTS: In total, 222 patients undergoing radical cytoreduction were analysed (48 patients for relapsed disease and 174 patients at primary diagnosis of advanced ovarian cancer). The range of surgical procedures was similar in both groups. In 48% of secondary cytoreductions 'optimal surgical results' (residual tumour <1 cm) were obtained and 33% of the patients had no residual disease compared to 82% and 58% at primary cytoreduction. There was no significant difference in perioperative complication rates. The duration of surgery was shorter and the number of transfused blood products was smaller at secondary cytoreduction (p < 0.001 and p = 0.001). CONCLUSION: Secondary cytoreduction in relapsed ovarian cancer is safe and feasible and perioperative outcome is not inferior compared to primary cytoreduction. Surgery-associated morbidity should represent a minor aspect in the selection and counselling of patients regarding treatment options for recurrent ovarian cancer.