Inverse scattering with a parametrized spatial spectral volume integral equation for finite scatterers.

In wafer metrology, the knowledge of the photomask together with the deposition process only reveals the approximate geometry and material properties of the structures on a wafer as a priori information. With this prior information and a parametrized description of the scatterers, we demonstrate the performance of the Gauss-Newton method for the precise and noise-robust reconstruction of the actual structures, without further regularization of the inverse problem. The structures are modeled as 3D finite dielectric scatterers with a uniform polygonal cross-section along their height, embedded in a planarly layered medium. A continuous parametrization in terms of the homogeneous permittivity and the vertex coordinates of the polygons is employed. By combining the global Gabor frame in the spatial spectral Maxwell solver with the consistent parametrization of the structures, the underlying linear system of the Maxwell solver inherits all the continuity properties of the parametrization. Two synthetically generated test cases demonstrate the noise-robust reconstruction of the parameters by surpassing the reconstruction capabilities of traditional imaging methods at signal-to-noise ratios up to -3d B with geometrical errors below λ/7, where λ is the illumination wavelength. For signal-to-noise ratios of 10 dB, the geometrical parameters are reconstructed with errors of approximately λ/60, and the material properties are reconstructed with errors of around 0.03%. The continuity properties of the Maxwell solver and the use of prior information are key contributors to these results.

Impact of risk-reducing salpingo-oophorectomy on lipid determinants, HbA1c and CRP.

OBJECTIVE: Risk-reducing salpingo-oophorectomy (RRSO) is advised before 40-45 years of age for BRCA1/2 mutation carriers. This study describes the effect of RRSO on lipid determinants, hemoglobin A1c (HbA1c) and C-reactive protein (CRP). METHODS: A total of 142 women with increased risk of ovarian cancer were included, 92 premenopausal and 50 postmenopausal. Serum levels of low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol and total cholesterol, triglycerides, HbA1c and CRP were determined at three points in time: before (T0) and 6 weeks (T1) and 7 months (T2) following RRSO. The Hot Flush Rating Scale was administered at the same time points. RESULTS: In premenopausal women, levels of HDL-cholesterol, the cholesterol ratio and HBA1c increased significantly over time, although still staying within the reference range. In this group, hot flushes increased over time (p < 0.001). In postmenopausal women, no significant changes were observed following RRSO. At T2, serum LDL-cholesterol, triglycerides, HbA1c and CRP were significantly lower in premenopausal women compared to postmenopausal women, whereas HDL was increased. CONCLUSIONS: Seven months after RRSO, the lipid profile in premenopausal women had changed, although still staying within the reference range. For postmenopausal women, we did not observe any significant changes. Our results do not suggest a worsening of cardiovascular risk within 7 months of RRSO.

Clinical outcomes of pelvic exenteration for gynecologic malignancies.

OBJECTIVES: The aim of this study was to analyze morbidity and survival after pelvic exenteration for gynecologic malignancies and evaluate prognostic factors influencing postoperative outcome. METHODS: We retrospectively reviewed all patients who underwent a pelvic exenteration at the departments of gynecologic oncology of three tertiary care centers in the Netherlands, the Leiden University Medical Centre, the Amsterdam University Medical Centre, and the Netherlands Cancer Institute, during a 20-year period. We determined postoperative morbidity, 2- and 5-year overall survival (OS) and 2- and 5-year progression free survival (PFS), and investigated parameters influencing these outcomes. RESULTS: A total of 90 patients were included. The most common primary tumor was cervical cancer (n = 39, 43.3%). We observed at least one complication in 83 patients (92%). Major complications were seen in 55 patients (61%). Irradiated patients had a higher risk of developing a major complication. Sixty-two (68.9%) required ≥1 readmission. Re-operation was required in 40 patients (44.4%). Median OS was 25 months and median PFS was 14 months. The 2-year OS rate was 51.1% and the 2-year PFS rate was 41.5%. Tumor size, resection margins and pelvic sidewall involvement had a negative impact on OS (HR = 2.159, HR = 2.376, and HR = 1.200, respectively). Positive resection margins and pelvic sidewall involvement resulted in decreased PFS (HR = 2.567 and HR = 3.969, respectively). CONCLUSION: Postoperative complications after pelvic exenteration for gynecologic malignancies are common, especially in irradiated patients. In this study, a 2-year OS rate of 51.1% was observed. Positive resections margins, tumor size, and pelvic sidewall involvement were related to poor survival outcomes. Adequate selection of patients who will benefit from pelvic exenteration is important.

Describing discontinuous finite 3D scattering objects in Gabor coefficients: fast and accurate methods.

In relation to the computation of electromagnetic scattering in layered media by the Gabor-frame-based spatial spectral Maxwell solver, we present two methods to compute the Gabor coefficients of the transverse cross section of three-dimensional scattering objects with high accuracy and efficiency. The first method employs the analytically obtained two-dimensional Fourier transform of the cross section of a scattering object, which we describe by two-dimensional characteristic functions, in combination with the traditional discrete Gabor transform method for computing the Gabor coefficients. The second method concerns the expansion of the so-called dual window function to compute the Gabor coefficients by employing the divergence theorem. Both methods utilize (semi)-analytical approaches to overcome the heavy oversampling requirement of the traditional discrete Gabor transform method in the case of discontinuous functions. Numerical results show significant improvement in terms of accuracy and computation time for these two methods against the traditional discrete Gabor transform method.

The state of the art in beyond 5G distributed massive multiple-input multiple-output communication system solutions.

Beyond fifth generation (5G) communication systems aim towards data rates in the tera bits per second range, with improved and flexible coverage options, introducing many new technological challenges in the fields of network architecture, signal pro- cessing, and radio frequency front-ends. One option is to move towards cell-free, or distributed massive Multiple-Input Multiple-Output (MIMO) network architectures and highly integrated front-end solutions. This paper presents an outlook on be- yond 5G distributed massive MIMO communication systems, the signal processing, characterisation and simulation challenges, and an overview of the state of the art in millimetre wave antennas and electronics.

Screening for intra-anal squamous intra-epithelial lesions in women with a history of human papillomavirus-related vulvar or perianal disease: results of a screening protocol.

AIM: Women with a history of human papillomavirus (HPV)-related cervical, vaginal or vulvar high-grade squamous intra-epithelial lesions (HSILs) or cancer are at increased risk of developing anal squamous intra-epithelial lesions (SILs) or a squamous cell carcinoma of the anus (SCCA). Screening for intra-anal SILs with high-resolution anoscopy (HRA) in high-risk populations is a subject of debate. In this study we aimed to answer the following question: what is the prevalence of intra-anal (H)SIL in women with HPV-related vulvar and/or perianal disease using HRA for screening? METHOD: A retrospective study was performed to evaluate the prevalence of intra-anal (H)SIL in women with a history of vulvar and/or perianal HSIL or (superficially invasive) squamous cell carcinoma (SCC). This study was performed between 2015 and 2018 following implementation of a protocol for intra-anal screening using HRA. RESULTS: Twenty-seven patients, 10 with a history of (superficially invasive) SCC (four vulvar, five perianal, one multizonal) and 17 with HSIL as the worst diagnosis (two perianal, 15 multizonal) were screened for intra-anal lesions using HRA. No anal cancer was found at screening, 6 (22%) patients were diagnosed with intra-anal HSIL and 12 (44%) patients with intra-anal low-grade SIL. CONCLUSIONS: We found a high prevalence of intra-anal HSIL in women previously diagnosed with vulvar and perianal HSIL. Given the clear link between HSIL and SCCA, screening for intra-anal lesions in women with HPV-related genital pathology seems warranted. Future studies should focus on the effect of HSIL treatment on the prevention of anal cancer.

Effects and moderators of coping skills training on symptoms of depression and anxiety in patients with cancer: Aggregate data and individual patient data meta-analyses.

PURPOSE: This study evaluated the effects of coping skills training (CST) on symptoms of depression and anxiety in cancer patients, and investigated moderators of the effects. METHODS: Overall effects and intervention-related moderators were studied in meta-analyses of pooled aggregate data from 38 randomized controlled trials (RCTs). Patient-related moderators were examined using linear mixed-effect models with interaction tests on pooled individual patient data (n = 1953) from 15 of the RCTs. RESULTS: CST had a statistically significant but small effect on depression (g = -0.31,95% confidence interval (CI) = -0.40;-0.22) and anxiety (g = -0.32,95%CI = -0.41;-0.24) symptoms. Effects on depression symptoms were significantly larger for interventions delivered face-to-face (p = .003), led by a psychologist (p = .02) and targeted to patients with psychological distress (p = .002). Significantly larger reductions in anxiety symptoms were found in younger patients (pinteraction < 0.025), with the largest reductions in patients <50 years (ß = -0.31,95%CI = -0.44;-0.18) and no significant effects in patients ≥70 years. Effects of CST on depression (ß = -0.16,95%CI = -0.25;-0.07) and anxiety (ß = -0.24,95%CI = -0.33;-0.14) symptoms were significant in patients who received chemotherapy but not in patients who did not (pinteraction < 0.05). CONCLUSIONS: CST significantly reduced symptoms of depression and anxiety in cancer patients, and particularly when delivered face-to-face, provided by a psychologist, targeted to patients with psychological distress, and given to patients who were younger and received chemotherapy.

Does anti-Müllerian hormone predict change in menopausal symptoms following risk-reducing salpingo-oophorectomy? A prospective observational study.

OBJECTIVES: The aim of this study was to investigate whether serum anti-Müllerian hormone (AMH) predicts symptom burden after risk-reducing salpingo-oophorectomy (RRSO) in order to individualize counseling. METHODS: Patient-reported menopausal symptoms, sexual functioning, and psychological distress (depression and anxiety) were assessed 1 day before (T0) and 6 weeks (T1) and 7 months (T2) after RRSO. AMH was assessed before RRSO. Multivariable regression analysis was used to investigate the association between AMH and short-term and long-term change in symptom burden following RRSO. RESULTS: Ninety-one premenopausal women at high risk of ovarian cancer were included. Presurgical AMH was not related significantly to change in symptoms post RRSO. As a secondary outcome we found that regular menses before RRSO was associated specifically with long-term increase in hot flushes (sr = 0.40, p = 0.001; total R2 = 0.171) and depression (sr = 0.29, p = 0.012; total R2 = 0.132). Earlier receipt of chemotherapy was associated with long-term improvement in sexual functioning (sr = 0.24, p = 0.041; total R2 = 0.348). CONCLUSION: In this cohort, AMH was not a significant predictor of change in symptoms following RRSO. Regular menses prior to RRSO and earlier receipt of chemotherapy were significantly, but relatively weakly, associated with changes in outcomes 6 weeks and/or 7 months after RRSO.

Characteristics of Lynch syndrome associated ovarian cancer.

OBJECTIVE: To describe clinical characteristics of Lynch syndrome associated ovarian cancer and the efficacy of surveillance in the early detection of these ovarian cancers. METHODS: All Lynch syndrome associated ovarian cancer cases identified in either the Dutch Lynch syndrome registry (DLSR) between 1987 and 2016, and/or the cohort at the University Medical Center Groningen (UMCG) between 1993 and 2016 were included. Clinical data on age at diagnosis, mutation type, histological type, FIGO stage, treatment, follow-up and gynecological surveillance were collected. RESULTS: A total of 46/798 (6%) women in the DLSR and 7/80 (9%) in the UMCG cohort were identified as LS associated ovarian cancer patients. The median age at ovarian cancer diagnosis was 46.0 years (range 20-75 years). The most frequently reported histological type was endometrioid adenocarcinoma (40%; n = 21) and serous carcinoma (36%; n = 19). Most tumors (87%; n = 46) were detected at an early stage (FIGO I/II). Forty-one of 53 (77%) patients were diagnosed with ovarian cancer before LS was diagnosed. In the other 12/53 (23%) women, ovarian cancer developed after starting annual gynecological surveillance for LS; three ovarian cancers were screen-detected in asymptomatic women. Overall survival was 83%. CONCLUSION: Ovarian cancer in women with LS has a wide age-range of onset, is usually diagnosed at an early stage with predominantly endometrioid type histology and a good overall survival. The early stage at diagnosis could not be attributed to annual gynecological surveillance.

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta-analysis of 22 RCTs.

OBJECTIVE: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. METHODS: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables. RESULTS: PSI significantly improved QoL (ß = 0.14,95%CI = 0.06;0.21), EF (ß = 0.13,95%CI = 0.05;0.20), and SF (ß = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. CONCLUSIONS: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.

Local normal vector field formulation for periodic scattering problems formulated in the spectral domain.

We present two adapted formulations, one tailored to isotropic media and one for general anisotropic media, of the normal vector field framework previously introduced to improve convergence near arbitrarily shaped material interfaces in spectral simulation methods for periodic scattering geometries. The adapted formulations enable the definition and generation of the normal vector fields to be confined to a region of prolongation that includes the material interfaces but is otherwise limited. This allows for a more flexible application of geometrical transformations like rotation and translation per scattering object in the unit cell. Moreover, these geometrical transformations enable a cut-and-connect strategy to compose general geometries from elementary building blocks. The entire framework gives rise to continuously parameterized geometries.

Optical biopsy of epithelial cancers by optical coherence tomography (OCT).

Optical coherence tomography (OCT) is an optical technique that measures the backscattering of near-infrared light by tissue. OCT yields in 2D and 3D images at micrometer-scale resolution, thus providing optical biopsies, approaching the resolution of histopathological imaging. The technique has shown to allow in vivo differentiation between benign and malignant epithelial tissue, through qualitative assessment of OCT images, as well as by quantitative evaluation, e.g., functional OCT. This study aims to summarize the principles of OCT and to discuss the current literature on the diagnostic value of OCT in the diagnosis of epithelial (pre)malignant lesions. The authors did a systematic search of the electronic databases PubMed and Embase on OCT in the diagnostic process of (pre)malignant epithelial lesions. OCT is able to differentiate between benign and (pre)malignant lesions of epithelial origin in a wide variety of tissues. In this way, OCT can detect skin cancers, oral, laryngeal, and esophageal cancer as well as genital and bladder cancer. OCT is an innovative technique which enables an optical biopsy of epithelial lesions. The incorporation of OCT in specific tools, like handheld and catheter-based probes, will further improve the implementation of this technology in daily clinical practice.

Outcome of BRCA1- compared with BRCA2-associated ovarian cancer: a nationwide study in the Netherlands.

BACKGROUND: Recent studies suggested an improved overall survival (OS) for BRCA2- versus BRCA1-associated epithelial ovarian cancer (EOC), whereas the impact of chemotherapy is not yet clear. In a nationwide cohort, we examined the results of primary treatment, progression-free survival (PFS), treatment-free interval (TFI), and OS of BRCA1 versus BRCA2 EOC patients. METHODS: Two hundred and forty-five BRCA1- and 99 BRCA2-associated EOC patients were identified through all Dutch university hospitals. Analyses were carried out with the Pearson's Chi-square test, Kaplan-Meier, and Cox regression methods. RESULTS: BRCA1 patients were younger at EOC diagnosis than BRCA2 patients (51 versus 55 years; P < 0.001), without differences regarding histology, tumor grade, and International Federation of Gynecology and Obstetrics (FIGO) stage. Complete response rates after primary treatment, including chemotherapy, did not differ between BRCA1 (86%) and BRCA2 patients (90%). BRCA1 versus BRCA2 patients had a shorter PFS (median 2.2 versus 3.9 years, respectively; P = 0.006), TFI (median 1.7 versus 2.8 years; P = 0.009), and OS (median 6.0 versus 9.7 years; P = 0.04). Differences could not be explained by age at diagnosis, FIGO stage or type of treatment. CONCLUSIONS: PFS and OS were substantially longer in BRCA2- than in BRCA1-associated EOC patients. While response rates after primary treatment were similarly high in both groups, TFI, as surrogate for chemosensitivity, was significantly longer in BRCA2 patients.

No evidence of benefit from class-II compression stockings in the prevention of lower-limb lymphedema after inguinal lymph node dissection: results of a randomized controlled trial.

Graduated compression stockings have been advocated for prevention of lymphedema after inguinal lymph node dissection (ILND) although scientific evidence of their efficacy in preventing lymphedema is lacking. The primary objective of this study was to assess the efficacy of class II compression stockings for the prevention of lymphedema in cancer patients following ILND. Secondary objectives were to investigate the influence of stockings on the occurrence of wound complications and genital edema, health-related quality of life (HRQoL) and body image. Eighty patients (45 with melanoma, 35 with urogenital tumors) who underwent ILND at two specialized cancer centers were randomly allocated to class II compression stocking use for six months or to a usual care control group. Lymphedema of the leg and genital area, wound complications, HRQoL, and body image were assessed at regular intervals prior to and up to 12 months after ILND. No significant differences were observed between groups in the incidence of edema, median time to the occurrence of edema, incidence of genital edema, frequency of complications, HRQoL, or body image. Based on the results of the current study, routine prescription of class II graduated compression stockings after ILND should be questioned and alternative prevention strategies should be considered.

Characteristics of breast cancer patients who experience menopausal transition due to treatment.

OBJECTIVE: To identify patient-related and treatment-related factors associated significantly with climacteric symptoms in young patients who experience menopausal transition due to adjuvant treatment for breast cancer. METHODS: This cross-sectional study used questionnaire data collected to screen breast cancer patients for participation in a multicenter trial on the efficacy of supportive interventions for treatment-induced menopausal symptoms. The screening instrument included questions on sociodemographics, menopausal history and current menopausal status and symptoms, treatment history and lifestyle factors. Univariate and multivariate analyses were used to identify factors associated significantly with two major menopausal symptoms, hot flushes/night sweats and vaginal dryness. RESULTS: In total, 435 patients were included in this study. Hot flushes/night sweats exhibited a significant, negative association with education and a significant positive association with alcohol consumption, and having been treated with the combination of chemotherapy and hormonal therapy. Vaginal dryness was positively associated with combined treatment with chemotherapy and hormonal therapy. CONCLUSIONS: Menopausal symptoms among young breast cancer patients who experience menopausal transition due to adjuvant treatment are associated with a number of sociodemographic, lifestyle and treatment-related factors. Carefully designed interventions to prevent or alleviate these symptoms should take these factors into account.

Work-related upper extremity disorders: one-year follow-up in an occupational diseases registry.

PURPOSE: To study the course and consequences of work-related upper extremity disorders in the registry of the Netherlands Centre for Occupational Diseases (NCvB). METHODS: A follow-up study was performed in a sample of consecutive cases of work-related upper extremity disorders notified to the NCvB. Perceived severity was measured with VAS (0-100), quality of life with VAS (0-100) and SF-36, functional impairment with DASH and sickness absence with a questionnaire. Measurements took place directly after notification (T0) and after 3, 6 and 12 months (T1-T3). A linear mixed model was used to compare scores over time. RESULTS: Average age of the 48 consecutive patients (89% response) was 42 years; 48% were men. Perceived severity, functional impairment and sickness absence decreased statistically significant during the follow-up period, and quality of life scores improved. Patients older than 45 years scored worse on perceived severity of the disease, functional impairment and quality of life than did younger patients. CONCLUSIONS: The role of registries of occupational diseases for preventive policy can be extended by creating longitudinal data in sample projects. In the sample from our registry, work-related upper extremity disorders had a favourable course.

Notification of occupational skin diseases by dermatologists in The Netherlands.

BACKGROUND: A voluntary surveillance scheme of occupational skin diseases (OSDs) in The Netherlands starting in 2001 aimed to improve insight in the incidence of OSD especially occupational contact dermatitis (OCD), risk professions and causal agents. This paper presents the results of this scheme during 2001-05. METHODS: Reports of new cases of OSD received from the participating dermatologists on a monthly basis were analysed. Data evaluated included information on diagnosis, sex, age, sickness, absenteeism, profession and causal agents. Relative differences in incidence rates between industries or branches were estimated by calculating incidence rate ratios. RESULTS: About 80% of the notifications concerned OCD. The highest number of notifications was recorded in the first year of the scheme. This was probably due to reporting of a mixture of incident and prevalent cases. During the following 5 years, the number of yearly notifications of OSD declined. Hairdressers, nurses, metalworkers, mechanics and cleaners were the most commonly affected professions. Wet work and irritating substances were the most frequently reported causal agents. Most patients with OCD were not absent from work. CONCLUSIONS: A voluntary surveillance scheme with dermatologists provides valuable data about the distribution of OCD in risk professions and the causal agents. However, it has certain limitations in assessing trends in incidence. Active medical surveillance in populations at risk should be encouraged not only to improve secondary prevention but also to obtain more reliable information about the incidence of OCD.

Diagnosing and reporting of occupational diseases: a quality improvement study.

AIM: To assess the need for quality improvement of diagnosing and reporting of noise-induced occupational hearing loss and occupational adjustment disorder. METHODS: Performance indicators and criteria for the quality of diagnosing and reporting were developed. Self-assessment questionnaires were sent to all occupational physicians recorded on the Netherlands Centre for Occupational Diseases database. The performance of responding occupational physicians was then assessed by separate scores per performance indicator and by a total quality score. RESULTS: Twenty-three questionnaires on noise-induced occupational hearing loss and 125 questionnaires on occupational adjustment disorder were available for analysis. The mean quality score for diagnosing and reporting was 6.0 (SD: 1.4) for noise-induced occupational hearing loss and 7.9 (SD: 1.5) for occupational adjustment disorder on a scale of 0-10. For noise-induced occupational hearing loss, there was a need for quality improvement of the aspects of medical history, audiometric measurement, clinical diagnosis of the disease and reporting. For occupational adjustment disorder, the assessment of other non-occupational causes needed improvement. CONCLUSIONS: The quality of diagnosing and reporting could be improved for noise-induced occupational hearing loss and occupational adjustment disorders. Information, education and practical tools are proposed for quality improvements.

No efficacy of annual gynaecological screening in BRCA1/2 mutation carriers; an observational follow-up study.

BRCA1/2 mutation carriers are offered gynaecological screening with the intention to reduce mortality by detecting ovarian cancer at an early stage. We examined compliance and efficacy of gynaecological screening in BRCA1/2 mutation carriers. In this multicentre, observational, follow-up study we examined medical record data of a consecutive series of 888 BRCA1/2 mutation carriers who started annual screening with transvaginal ultrasonography and serum CA125 between 1993 and 2005. The women were annually screened for 75% of their total period of follow-up. Compliance decreased with longer follow-up. Five of the 10 incident cancers were interval tumours, diagnosed in women with a normal screening result within 3-10 months before diagnosis. No difference in stage distribution between incident screen-detected and interval tumours was found. Eight of the 10 incident cancers were stage III/IV (80%). Cancers diagnosed in unscreened family members had a similar stage distribution (77% in stage III/IV). The observed number of cases detected during screening was not significantly higher than expected (Standardized Incidence Ratio (SIR): 1.5, 95% confidence interval: 0.7-2.8). For the subgroup that was fully compliant to annual screening, a similar SIR was found (1.6, 95% confidence interval: 0.5-3.6). Despite annual gynaecological screening, a high proportion of ovarian cancers in BRCA1/2 carriers are interval cancers and the large majority of all cancers are diagnosed in advanced stages. Therefore, it is unlikely that annual screening will reduce mortality from ovarian cancer in BRCA1/2 mutation carriers.

In the absence of (early) invasive carcinoma, vulvar intraepithelial neoplasia associated with lichen sclerosus is mainly of undifferentiated type: new insights in histology and aetiology.

BACKGROUND: Differentiated vulvar intraepithelial neoplasia (VIN) is presumed to be the precursor of invasive squamous cell carcinoma (SCC) of the vulva. It is commonly assumed that differentiated VIN is related to lichen sclerosus (LS). However, evidence for this is limited to a small number of studies describing epithelial alterations adjacent to vulvar SCC. AIM: To study the histology and human papillomavirus (HPV) status in patients with a history of both LS and VIN without coexistent SCC. METHODS: Original biopsy specimens and surgical specimens of patients retrieved from the pathology files were revised for the presence of LS, VIN and (early) invasive SCC, specifically focused on the two different types of VIN: differentiated and undifferentiated. Thereafter, VIN lesions were tested for the presence of HPV DNA. RESULTS: Twenty-seven patients fulfilled the criteria for LS and VIN without SCC. In all 27 patients, LS was found to be related to undifferentiated VIN. Grading yielded the following results: VIN 1 (n=10), VIN 2 (n=11) and VIN 3 (n=6). Additionally, VIN lesions from 26 patients could be tested for the presence of HPV DNA. HPV DNA, predominantly type 16, was present in 8 (31%) of them. Seven of these eight patients had VIN 2 or 3. During follow-up, three patients progressed to (early) invasive carcinoma. In two of these patients, differentiated VIN was observed overlying early invasive SCC. CONCLUSIONS: VIN related to LS without coexisting SCC is likely to be undifferentiated, in contrast to what was previously thought. HPV DNA was demonstrated in 31% of the lesions, and was strongly related to high-grade VIN.