Retrospective cohort study on the bilateral occurrence of invasive lobular breast cancer.

OBJECTIVE: Invasive lobular carcinoma (ILC) is the second most common histological subtype of invasive breast cancer, following the no special type (NST) invasive carcinoma. It has historically been assumed that ILC occurs bilaterally in 20-29 % of cases, which has influenced the inclusion of MRI in the standard workup of ILC according to European guidelines. However, challenging this long-held belief regarding the bilateral occurrence of ILC opens up the possibility of revising the guidelines and using MRI only for more specific indications. This study aims to evaluate whether the previously reported high percentage of bilaterality still holds true and to question the added value of MRI in the standard workup of ILC. STUDY DESIGN: A retrospective cohort study was conducted following approval from the institutional review board (EC 21/18/249) at Antwerp University Hospital (UZA). The cohort comprised female patients of all ages who had been diagnosed with either ILC or NST invasive carcinoma and had sought consultation at the UZA breast clinic. A comprehensive database was established to collect information on patient characteristics, imaging, and pathology. RESULTS: A total of 271 patients with ILC were included in the study, with incidence dates ranging from 01/01/2007 to 01/01/2023. Among these patients, a synchronous bilateral ILC lesion was observed in 1.85 % (5/271) of cases. This proportion is significantly lower than the reported percentage of patients with a bilateral lesion in the literature population, which stands at 4.95 %. The reference group consisted of 809 patients with NST invasive carcinoma, with incidence dates ranging from 01/01/2017 to 01/01/2023. In the control group, a synchronous bilateral NST lesion was observed in 3.96 % (32/809) of cases. There is no significant difference in the bilaterality rates between the group of ILC patients and the group of NST patients. Furthermore, MRI did not detect any histopathologically confirmed contralateral ILC lesion that had not already been detected by mammography or ultrasound. CONCLUSIONS: The study results indicate a lower occurrence of bilateral ILC than previously assumed. Additionally, the incidence of synchronous bilateral lesions in ILC patients is not higher compared to patients with NST invasive carcinoma. Performing an MRI does not provide additional value in detecting bilateral carcinomas in ILC. Consequently, it is recommended that the current European guidelines be reassessed, and the indications for undergoing an MRI should be adjusted accordingly.

Literature review on the bilateral occurrence of invasive lobular breast cancer.

Historically, it has been believed that invasive lobular carcinomas (ILC) occur more frequently bilaterally compared to other invasive subtypes, with estimates ranging between 20% and 29%. This study aims to determine if this historical perspective still holds true. A comprehensive literature review was conducted to examine the bilateral occurrence of lobular carcinoma using various imaging methods. Additionally, the role of magnetic resonance imaging (MRI) in detecting contralateral carcinomas was also investigated. A comprehensive search was conducted in the MedLine database on the PubMed platform, resulting in 307 articles published between January 1, 2014, and January 1, 2023. Various selection criteria were applied to identify articles relevant to the research question. After careful assessment, eight articles remained that met the eligibility criteria, all of which provided level-three evidence and were therefore included in the literature review. A total of 599 patients were included in this review, comprising a total of 602 cases of ILC. Six out of the eight articles reviewed provided information on the bilateral occurrence of ILC based on histopathology. A weighted average calculation yielded a bilaterality percentage of 4.95% (24 out of 485 cases). Four articles reported the number of bilateral cases identified through MRI, resulting in a weighted average of 10.2% (26 out of 255 cases). It is worth noting that 20.4% (100 out of 491) of the performed MRIs were found to be either useless or even harmful. Furthermore, MRI led to a change in the treatment plan in 27.7% (136 out of 491) of cases. Overall, it can be concluded that there is limited available data regarding the bilateral occurrence of ILC. The numbers found in the literature are also inconsistent and tend to vary. The literature review revealed a decrease in the percentage of bilaterality compared to historical beliefs. Based on this study, it can be concluded that a high number of MRI scans were found to be either useless or harmful. As a result of this conclusion and a higher sensitivity of other screening modalities, MRI may no longer be indicated as part of the standard workup for ILC. However, further research is necessary to validate these findings.

Follow-up of humoral immune response after HPV vaccination using first-void urine: A longitudinal cohort study.

Assessment of humoral immune responses following human papillomavirus (HPV) vaccination currently relies on invasive blood sampling. This longitudinal cohort study explores the usability of first-void urine as a noninvasive alternative sample for antibody detection. In this study, 58 women receiving three doses of the 9vHPV vaccine within a Gardasil9 (9vHPV) Phase III randomized controlled trial were included. Participants provided paired first-void urine and blood samples before vaccination (M0), 1 month after the third dose (M7), and ~3 years after the third dose (M43). Type-specific antibody responses to the 9vHPV types were analyzed in 174 first-void urine and 172 serum samples using a virus-like particle-based IgG multiplex enzyme-linked immunosorbent assay. Additionally, total human IgG concentrations were determined using the BioPlex assay. At M7, 1 month after complete 9vHPV vaccination, 95%-100% of first-void urine and 100% of serum samples had detectable concentrations, varying by HPV type. At M43, 84%-100% of first-void urine and 98%-100% of serum samples had HPV-specific antibody concentrations. Results show significant Spearman rank correlations between type-specific HPV-antibody concentrations for paired first-void urine and serum at all time points. This study confirms the potential feasibility of utilizing first-void urine as a noninvasive immunological sample within HPV vaccine trials.

The evolution of breast reconstructions with free flaps: a historical overview.

BACKGROUND: Breast cancer is the most frequent cancer among women and is responsible for the highest number of cancer-related deaths. Approximately 40% of the patients with breast cancer will undergo a mastectomy. Breast amputation is a lifesaving but mutilating procedure. Therefore a good quality of life and a good cosmetic outcome is mandatory after breast cancer treatment. Reconstructive breast surgery aims to recreate a natural looking breast that is warm, soft and feels natural. The chosen reconstruction technique depends on the physiognomy of the patient, technical skills of the surgeon and most important the expectations of the patient. RESULTS: The idea of 'like-by-like' replacement refers to reconstruction of a natural-looking, warm, soft and ptotic breast that matches the contralateral side. Autologous breast-reconstruction matches these expectations. Autologous breast reconstructions with free flaps evolved from prolonged and laborious procedures with only limited free flaps available, to routine surgeries with a widespread availability of flaps to use. The first publication of free tissue transfer for breast reconstruction was in 1976 by Fujino. Two years later Holmström was the first to use the abdominal pannus for breast reconstruction. Over the next four decades multiple free flaps have been described. The possible options for donor site are the abdomen, the gluteal region, the thigh and the lower back. During this evolution the reduction of donor site morbidity became more important. CONCLUSION: Present article gives an overview of the evolution of free tissue transfer in breast reconstruction, highlighting the most important milestones.

The Effectiveness of Fluoroscopy-Guided Manual Lymph Drainage as Part of Decongestive Lymphatic Therapy on the Superficial Lymphatic Architecture in Patients with Breast Cancer-Related Lymphoedema: A Randomised Controlled Trial.

The objective of this trial was to investigate the effectiveness of fluoroscopy-guided manual lymph drainage (MLD), as part of decongestive lymphatic therapy (DLT), on the superficial lymphatic architecture in patients with chronic mild to moderate breast cancer-related lymphoedema (BCRL). This trial was a multicentre, double-blind, randomised controlled trial involving 194 participants with BCRL. Participants were randomised into (1) DLT with fluoroscopy-guided MLD (intervention group), (2) DLT with traditional MLD (control group), or (3) DLT with placebo MLD (placebo group). Superficial lymphatic architecture was evaluated as a secondary outcome, visualised by ICG lymphofluoroscopy at the baseline (B0), post-intensive (P), and post-maintenance phases (P6). Variables were (1) number of efferent superficial lymphatic vessels leaving the dermal backflow region, (2) total dermal backflow score, and (3) number of superficial lymph nodes. The traditional MLD group showed a significant decrease in the number of efferent superficial lymphatic vessels at P (p = 0.026), and of the total dermal backflow score at P6 (p = 0.042). The fluoroscopy-guided MLD and placebo group showed significant decreases in the total dermal backflow score at P (p < 0.001 and p = 0.044, respectively) and at P6 (p < 0.001 and p = 0.007, respectively); the placebo MLD group showed a significant decrease in the total number of lymph nodes at P (p = 0.008). However, there were no significant between-group differences for the changes in these variables. In conclusion, based on lymphatic architecture outcomes, the added value of MLD, in addition to the other parts of DLT, could not be demonstrated in patients with chronic mild to moderate BCRL.

Does Manual Lymphatic Drainage Add Value in Reducing Suprafascial Fluid Accumulation and Skin Elasticity in Patients With Breast Cancer-Related Lymphedema?

OBJECTIVE: The purpose of this study was to investigate the effectiveness of fluoroscopy-guided manual lymph drainage (MLD) versus that of traditional and placebo MLD, when added to decongestive lymphatic therapy (DLT) for the treatment of breast cancer-related lymphedema (BCRL) (EFforT-BCRL trial), on the suprafascial accumulation of lymphatic fluid and skin elasticity. METHODS: In this multicenter, 3-arm, double-blind, randomized controlled trial (EFforT-BCRL trial), 194 participants (mean age = 61 [SD = 10] years) with unilateral BCRL were recruited. All participants received standardized DLT (education, skin care, compression therapy, exercises) and were randomized to fluoroscopy-guided, traditional, or placebo MLD. Participants received 60 min/d of treatment during the 3-week intensive phase and 18 sessions of 30 minutes during the 6-month maintenance phase. During this phase, participants were instructed to wear a compression garment, to perform exercises, and to perform a self-MLD procedure once daily. This study comprises secondary analyses of the EFforT-BCRL trial. Outcomes were the amount of fluid accumulation in the suprafascial tissues (local tissue water, extracellular fluid, and thickness of the skin and subcutaneous tissue) and skin elasticity at the level of the arm and trunk. Measurements were performed at baseline; after intensive treatment; after 1, 3, and 6 months of maintenance treatment; and after 6 months of follow-up. RESULTS: At the level of the arm, there was a significant improvement over time in the 3 groups for most of the outcomes. At the level of the trunk, no remarkable improvement was noted within the individual groups. No significant interaction effects (between-group differences) were present. Only skin elasticity at the level of the arm, evaluated through palpation, showed a significant interaction effect. CONCLUSION: All 3 groups showed similar improvements in response to DLT regardless of the type of MLD that was added. The effect of the addition of MLD to other components of DLT for reducing local tissue water and extracellular fluid or skin thickness and for improving skin elasticity and fibrosis in participants with chronic BCRL was limited. IMPACT: Although MLD has been applied all over the world for many years, evidence regarding its added value in reducing arm volume in patients with BCRL is lacking. These results show that adding MLD to other components of DLT has limited value in reducing local tissue water and extracellular fluid or skin thickness and in improving skin elasticity and fibrosis in patients with chronic BCRL. To date, there is no clinical indication to continue including time-consuming MLD in physical therapist sessions for patients with chronic BCRL.

Clinical Performance of the RealTime High Risk HPV Assay on Self-Collected Vaginal Samples within the VALHUDES Framework.

The VALHUDES framework (NCT03064087) was established to evaluate the clinical accuracy of HPV testing on self-samples compared with HPV testing on matched clinician-taken cervical samples. Women referred to colposcopy due to previous cervical abnormalities were recruited at five Belgian colposcopy centers. A total of 486 pairs of matched cervical samples and vaginal self-samples were included in the analysis (228 collected with Evalyn Brush and 258 with Qvintip). The dry vaginal brushes were transferred into 20 mL ThinPrep PreservCyt solution. All specimens were tested with the Abbott RealTime High Risk HPV assay (Abbott RT). Testing on vaginal and cervical specimens was considered the index and comparator tests, respectively, and colposcopy and histology as the reference standard. The clinical sensitivity for CIN2+ of Abbott RT (cutoff ≤32 cycle number [CN]) on vaginal self-samples (Evalyn Brush and Qvintip combined) was 8% lower than on the cervical clinician-collected samples (ratio = 0.92 [95% CI, 0.87 to 0.98]), while the specificity was similar (ratio = 1.04 [95% CI, 0.97 to 1.12]). Sensitivity (ratio = 0.95 [95% CI, 0.89 to 1.02]) and specificity (ratio = 1.11 [95% CI, 0.995 to 1.23]) on Evalyn Brush samples was similar to cervical, while on Qvintip samples, the sensitivity was 12% lower than cervical samples (ratio = 0.88 [95% CI, 0.78 to 0.998]) with similar specificity (0.99 [95% CI, 0.90 to 1.10]). Exploratory cutoff optimization (cutoff ≤35 CN) resulted in an improvement of the relative sensitivity (self-sampling versus clinician sampling: ratio = 0.96 [95% CI, 0.91 to 1.02]) but yielded a loss in relative specificity (ratio = 0.92 [0.85 to 1.00]). The clinical accuracy of Abbott RT differed from the self-sampling device. However, after cutoff optimization, the sensitivity on self-samples taken with either of two vaginal brushes became similar to clinician-collected samples. IMPORTANCE Self-samples are becoming a crucial part of HPV-based cervical cancer screening programs to reach nonattendee women and increase screening coverage. Therefore, the VALHUDES framework was established to validate and evaluate HPV tests and devices on self-samples. Here, in the present manuscript, we evaluated the accuracy of the RealTime High Risk HPV assay (Abbott RT) on two different vaginal devices to detect cervical intraepithelial neoplasia grade two or higher (CIN2+). The study results demonstrated that the Abbott RT assay is similarly accurate on vaginal self-samples as on matched clinician-taken cervical samples after adjusting cutoff values. Moreover, we observed that some vaginal devices perform better than others in CIN2+ detection. We also underline the necessity of standardization and validation of general workflow and sample handling procedures for vaginal self-samples.

Analytical and clinical performance of extended HPV genotyping with BD Onclarity HPV Assay in home-collected first-void urine: A diagnostic test accuracy study.

BACKGROUND: Urine collection is a non-invasive self-sampling method offering the prospect of reaching women un(der)-screened for cervical cancer. The VALHUDES research framework was designed to address the lack of clinical accuracy data for high-risk (hr)HPV testing using urine samples. OBJECTIVES: Here, we report on the analytical and clinical accuracy of hrHPV testing on first-void urine, collected at home, using an extended HPV genotyping assay. STUDY DESIGN: Paired first-void urine (Colli-Pee with UCM, Novosanis; index test) and clinician-collected cervical samples (Cervex-Brush, Rovers in PreservCyt Solution, Hologic; comparator test) were collected from 492 women aged 19 to 72 years attending colposcopy (reference test, with histology if indicated) (VALHUDES; NCT03064087). Extended HPV genotyping was performed on paired samples with the BD Onclarity HPV Assay. Cut-offs defined for cervical samples were also applied for first-void urine. RESULTS: HrHPV testing in first-void urine was similarly sensitive for both CIN2+ (ratio 1.00; 95% CI: 0.93-1.07) and CIN3 (ratio 0.98; 95% CI: 0.88-1.08), and marginally less specific for

Skin Cancer Detection Using Infrared Thermography: Measurement Setup, Procedure and Equipment.

Infrared thermography technology has improved dramatically in recent years and is gaining renewed interest in the medical community for applications in skin tissue identification applications. However, there is still a need for an optimized measurement setup and protocol to obtain the most appropriate images for decision making and further processing. Nowadays, various cooling methods, measurement setups and cameras are used, but a general optimized cooling and measurement protocol has not been defined yet. In this literature review, an overview of different measurement setups, thermal excitation techniques and infrared camera equipment is given. It is possible to improve thermal images of skin lesions by choosing an appropriate cooling method, infrared camera and optimized measurement setup.

If prophylactic HPV vaccination is considered in a woman with CIN2+, what is the value and should it be given before or after the surgical treatment?

Since the introduction of human papilloma virus (HPV) vaccination, the number of precancerous lesions has decreased in countries with a high HPV vaccination coverage. Currently women who present with a precancerous cervical lesions (CIN2 + ), are often not vaccinated or not vaccinated with the latest vaccine. Although resection of the precancerous lesion is the standard approach, the guidelines regarding vaccination are not clear. Vaccination will be valuable in reducing the risk of recurrence. Therefore, it is beneficial to understand the importance of vaccination or revaccination with the nonavalent vaccine in these cases. Furthermore, the timing of vaccination, either before or after surgery, should be determined. To answer these questions, twelve studies regarding vaccination and conization were reviewed. The inconsistency of study designs and inclusion criteria between the different studies introduced a considerable risk of bias. Nevertheless, the analysis showed that 43 women needed to be vaccinated and treated for CIN2 + lesions to prevent a recurrence. The ideal timing could not be established, but theoretically vaccination before the start of treatment was most logic. Although the data is not level 1 evidence, these recommendations should be used during counseling in the clinical setting until results of ongoing randomized controlled trials become available.

The Evolution and Prognostic Role of Tumour-Infiltrating Lymphocytes and Peripheral Blood-Based Biomarkers in Inflammatory Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

INTRODUCTION: Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer (BC) in which the (prognostic) role of stromal tumour-infiltrating lymphocytes (sTIL) and the peripheral circulating immune cells in patients with residual disease (RD) after neo-adjuvant chemotherapy (NACT) is not clearly established. METHODOLOGY: To describe the evolution of sTIL and some peripheral inflammation markers (Neutrophil-to-lymphocyte ratio, Platelet-to-lymphocyte ratio and Lymphocyte-to-monocyte ratio) after NACT in IBC, we retrospectively collected clinicopathological variables for 125 stage III IBC patients. sTILs were scored by three different researchers on an H&E slide of the mastectomy specimen. A cohort of subtype-matched non-IBC breast cancer patients (nIBC) treated with NACT was included for comparison. RESULTS: There was no significant difference in the pre- and posttreatment sTIL scores between IBC and nIBC and in both groups the number of sTIL was significantly lower after NACT. However, the IBC phenotype did correlate with a stronger decrease of sTIL after NACT (OR: 0.25, 95% CI: 0.073-0.76, p = 0.018). The change in the peripheral immune markers was not significantly different between IBC and nIBC. After NACT, 75 patients had residual disease. In this group, a high number of sTIL before NACT (HR: 0.23, 95% CI: 0.05-1.02, p = 0.05) was prognostic for a longer OS, while a low number of sTIL after NACT (HR: 0.33, 95% CI: 0.11-0.98, p = 0.046) and a low residual cancer cellularity (HR: 0.20, 95% CI: 0.08-0.52, p < 0.001) was associated with a longer DFS. CONCLUSIONS: IBC is associated with a significantly stronger decrease of sTIL after NACT compared to nIBC. Furthermore, a high number of sTIL after NACT was associated with a worse prognosis in IBC.

Cervical cancer screening using HPV tests on self-samples: attitudes and preferences of women participating in the VALHUDES study.

BACKGROUND: Interventions to reach women who do not participate regularly in screening may reduce the risk of cervical cancer. Self-collection of a vaginal specimen has been shown to increase participation. The relative clinical accuracy of human papillomavirus (HPV) testing on first-void urine (with Colli-Pee) and on vaginal self-samples versus on cervical clinician-collected samples is being investigated in the VALHUDES trial. The current study assesses attitudes and experiences regarding self-sampling among women enrolled in VALHUDES. METHODS: Questionnaires from 515 women (age 25-64 years [N = 498]; < 25 [N = 10], age ≥ 65 [N = 3], enrolled between December 2017 - January 2020) referred to colposcopy because of previous cervical abnormalities and enrolled in VALHUDES (NCT03064087) were analysed. RESULTS: Of the 515 participants, nearly all women confirmed that self-sampling may help in reaching under-screened women (93%). Nevertheless, 44% of the participants stated before starting collection that a clinician-collected sample is more effective than a self-collected sample. After self-sampling, the large majority of women (> 95%) declared that instructions for self-collection were clear, that collection was easy, and that they were confident about having performed the procedure correctly, for both urine and vaginal collection. However, a proportion of women found self-sampling unpleasant (9.5% [49/515] for urine collection; 18.6% [96/515] and 15.5% [80/515] for vaginal sampling with cotton swabs or plastic brushes, respectively). For their next screening round, 57% would prefer self-sampling whereas 41% opted for collection by a clinician. Among women preferring self-sampling, 53% would choose for urine collection, 38% for vaginal self-collection and 9% had no preference. Age did not modify preferences. CONCLUSION: We conclude that both urine and vaginal self-sampling are well accepted by women, with a preference for urine sampling. Although the large majority of women are confident in their ability to perform self-sampling, four to five over ten women preferred specimen collection by a clinician. TRIAL REGISTRATION: The study VALHUDES was registered in ClinicalTrials.gov (identifier: NCT03064087 ).

Clinical and analytical evaluation of the RealTime High Risk HPV assay in Colli-Pee collected first-void urine using the VALHUDES protocol.

OBJECTIVE: Urine self-sampling has gained increasing interest for cervical cancer screening. In contrast to analytical performance, little information is available regarding the clinical accuracy for high-risk Human Papillomavirus (hrHPV) testing on urine. METHODS: VALHUDES is a diagnostic test accuracy study comparing clinical accuracy to detect high-grade cervical precancer (CIN2+) of HPV testing on self-collected compared to clinician-collected samples (NCT03064087). Disease outcome was assessed by colposcopy and histology. The Abbott RealTime High Risk HPV assay performance was evaluated on Colli-Pee collected first-void urine with cervical outcomes as comparator. RESULTS: As no assay cut-off for urine has been clinically validated, we used the predefined cut-off for cervical samples (CN ≤ 32). Using this cut-off, hrHPV testing was similarly sensitive (relative sensitivity 0.95; 95% CI: 0.88-1.01) and specific (relative specificity 1.03; 95% CI: 0.95-1.13) for detection of CIN2+ compared to testing cervical samples. In the subgroup of women of 30 years and older, similar relative sensitivity (0.97; 95% CI: 0.89-1.05) and specificity (1.02; 95% CI: 0.93-1.12) was found. Additionally, an exploratory cut-off (CN ≤ 33.86) was defined which further improved sensitivity and analytical test performance. CONCLUSION: HrHPV-DNA based PCR testing on home-collected first-void urine has similar accuracy for detecting CIN2+ compared to cervical samples taken by a clinician.

Triage of human papillomavirus infected women by methylation analysis in first-void urine.

Host cell DNA methylation analysis in urine provides promising triage markers for women diagnosed with a high-risk (HR) human papillomavirus (HPV) infection. In this study, we have investigated a panel of six host cell methylation markers (GHSR, SST, ZIC1, ASCL1, LHX8, ST6GALNAC5) in cervicovaginal secretions collected within the first part of the urine void (FVU) from a referral population. Cytology, histology, and HPV DNA genotyping results on paired FVU and cervical samples were available. Urinary median methylation levels from HR-HPV (n = 93) positive women were found to increase for all markers with severity of underlying disease. Significantly elevated levels were observed for GHSR and LHX8 in relation to high-grade cervical intraepithelial neoplasia (CIN2 +; n = 33), with area under de curve values of 0.80 (95% Confidence Interval (CI) 0.59-0.92) and 0.76 (95% CI 0.58-0.89), respectively. These findings are the first to support the assertion that methylation analysis of host cell genes is feasible in FVU and holds promise as molecular, triage strategy to discern low- from high-grade cervical disease in HR-HPV positive women. Molecular testing on FVU may serve to increase cervical cancer screening attendance in hard-to-reach populations whilst reducing loss to follow-up and await further optimization and validation studies.

Immunogenicity and safety of a nine-valent human papillomavirus vaccine in women 27-45 years of age compared to women 16-26 years of age: An open-label phase 3 study.

BACKGROUND: Efficacy of the nine-valent human papillomavirus (9vHPV; HPV types 6/11/16/18/31/33/45/52/58) vaccine was demonstrated in a phase 3 study in women 16-26 years of age. We present a phase 3 immunogenicity and safety study of the 9vHPV vaccine in women 27-45 versus 16-26 years of age. METHODS: This international, open-label study (NCT03158220) was conducted in women 16-45 years of age. Participants (16-26 years, n = 570 and 27-45 years, n = 642) received a three-dose 9vHPV vaccination regimen (day 1, month 2, month 6). Month 7 geometric mean titers (GMTs) and seroconversion percentages to anti-HPV 6/11/16/18/31/33/45/52/58 were assessed. Participants were followed for safety throughout the study. RESULTS: At month 7, anti-HPV 6/11/16/18/31/33/45/52/58 GMTs in women 27-45 years were compared to those in women 16-26 years of age. The primary hypothesis of non-inferiority of anti-HPV 16/18/31/33/45/52/58 GMTs in older versus younger women was met. The lower bound of the GMT ratio 95% confidence interval (27-45 years to 16-26 years) was 0.60-0.67 depending on HPV type, exceeding the non-inferiority margin of 0.5 for all HPV types. Month 7 seroconversion percentages in women 27-45 years of age were >99% for all HPV types. Injection-site and vaccine-related systemic adverse events (AEs) were observed in 87.5% and 25.1% of women 16-26 years, and 85.2% and 24.1% of women 27-45 years of age, respectively; no vaccine-related serious AEs were reported and no deaths occurred during the study. CONCLUSIONS: The 9vHPV vaccine elicited non-inferior anti-HPV GMTs in women 27-45 years compared with women 16-26 years of age for HPV 16/18/31/33/45/52/58. The vaccine was generally well tolerated with a similar AE profile across the age groups. These data support bridging 9vHPV vaccine efficacy findings in women 16-26 years to women 27-45 years of age. Clinical trial registration NCT03158220.

Mycosis fungoides of the vulva.

Mycosis fungoides (MF) is an indolent form of non-Hodgkin lymphoma and the most common type of primary cutaneous T-cell lymphoma. The overall incidence of MF is approximately 4 per 1 million. Involvement of the vulva by MF is extremely rare, with only seven reported cases in the literature. At the vulva, it is mainly a metastatic lesion and rarely a primary malignancy. We describe a case of vulvar MF and discuss the previous cases. The presentation can easily be confused with benign skin disorders. A vulvar lesion can reflect a systemic disease. When a patient consults for a vulvar lesion it is therefore important not only to look at the vulva but also to examine her in and ask general questions. In a patient with a vulvar mass and cutaneous lesions on other locations MF should be considered in the differential diagnosis.

Cross-cultural validation of the French version of the Lymphedema Functioning, Disability and Health Questionnaire for Upper Limb Lymphedema (Lymph-ICF-UL).

PURPOSE: Upper limb lymphedema is a vexing morbidity that can occur after the treatment for breast cancer. The Lymphedema Functioning, Disability and Health Questionnaire for Upper Limb Lymphedema (Lymph-ICF-UL) is a valid and reliable tool assessing problems in functioning in patients with breast cancer-related lymphedema. Until now, a French-language version was lacking. The aim of this study was to perform a cross-cultural validation of the French version of the Lymph-ICF-UL questionnaire. METHODS: A forward-backward translation process between the original language (Dutch) and the target language (French) was performed. Psychometric properties of this final French version were examined in 50 participants. RESULTS: Intraclass correlation coefficients for test-retest reliability ranged from 0.66 to 0.95. Cronbach's alpha coefficients for internal consistency were higher than 0.77. Face and content validity were very good because the scoring system was clear for all participants (100%), questions were understandable (100%), and all complaints due to BCRL were mentioned by 78% of the participants. Construct validity was moderate. Convergent validity was established since 3 out of 5 expected domains of the Lymph-ICF-UL showed a moderate correlation with expected domains of the 36-item Short-Form Health Survey. There was satisfactory divergent validity as 6 out of 9 hypotheses assessing divergent validity were accepted. CONCLUSION: The French version of the Lymph-ICF-UL is a reliable and valid questionnaire and ready for use in clinical as well as in scientific practice.Implications for rehabilitationSince the introduction of more effective treatment modalities increasing the number of breast cancer survivors, the amount of patients dealing with lymphedema is rising likewise up to a pooled incidence rate of more than 16% of the women treated for breast cancer.The French version of the Lymph-ICF-UL is a reliable and valid questionnaire for assessing problems in functioning of patients with breast cancer-related lymphedema of the arm and/or hand.As the questionnaire provides patient information in the different domains of the International Classification of Functioning, Disability and Health, it facilitates evaluating the impact of breast cancer-related lymphedema on daily functioning.Based on the outcomes of the Lymph-ICF-UL treatment goals can be set, where after the questionnaire can be used to monitor long-term results of this treatment and self-care.