Biopsy-verified vulvar lichen sclerosus: Incidence trends 1997-2022 and increased risk of vulvar squamous precancer and squamous cell carcinoma.

Population-based data on the epidemiology of vulvar lichen sclerosus (LS) are sparse and only few prospective studies have investigated the malignant potential of the disease. We used the nationwide Danish Pathology Registry to first assess the incidence of biopsy-verified vulvar LS in the period 1997-2022 and second to examine the incidence of vulvar high-grade squamous precancer and squamous cell carcinoma (SCC) in women with biopsy-verified vulvar LS (1978-2019) compared with that expected in the general female population. For the latter aim, we computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). During our study period, the age-standardized incidence rate of vulvar LS increased from 5.0 (1997-1998) to 35.7 (2021-2022) per 100,000 person-years. Compared with the general female population, women with biopsy-verified vulvar LS had significantly increased rates of vulvar high-grade squamous precancer (SIR = 8.5; 95% CI: 7.2-10.0) and SCC (SIR = 16.2; 95% CI: 14.2-18.4). The SIRs of vulvar high-grade squamous precancer and SCC did not vary substantially according to length of follow-up. This nationwide and population-based study shows a 7-fold increase in the incidence of biopsy-verified vulvar LS since 1997. Data also show that women with biopsy-verified vulvar LS have 8.5 and 16 times higher than expected incidence of vulvar high-grade squamous precancer and SCC, respectively. The substantially increased incidence of vulvar high-grade squamous precancer and SCC following LS is important in relation to the clinical management and follow-up of LS patients.

Prediagnostic use of menopausal hormone therapy and long-term survival of localized epithelial ovarian cancer: The Extreme study.

Use of menopausal hormone therapy (MHT) prior to an epithelial ovarian cancer (EOC) diagnosis has been suggested to be associated with improved survival. In a recent nationwide cohort study, we found that prediagnostic long-term MHT use, especially estrogen therapy (ET), was associated with improved long-term survival in women with nonlocalized EOC. Our aim was to investigate the influence of prediagnostic MHT use on long-term survival among women with localized EOC in the same nationwide study. Our study cohort comprised all women aged 50 years or older with an EOC diagnosis in Denmark 2000-2014 (n = 2097) identified from the Extreme study. We collected information on usage of systemic ET and estrogen plus progestin therapy (EPT) from the Danish National Prescription Registry. By using pseudo-values, 5- and 10-year absolute and relative survival probabilities were estimated with 95% confidence intervals (CIs) while adjusting for histology, comorbidity, and income. Relative survival probabilities >1 indicate better survival. The 5-year absolute survival probabilities were 61% and 56%, respectively, among women who were nonusers and users of prediagnostic MHT, whereas these numbers were 46% and 41%, respectively, regarding 10-year survival. Use of MHT was not significantly associated with an improved 5- or 10-year survival in women with localized EOC (5-year relative survival probability = 0.95, 95% CI: 0.89-1.02; 10-year relative survival probability = 0.92, 95% CI: 0.84-1.02). Similar findings were seen for systemic ET or EPT use. Our findings do not suggest a positive benefit from prediagnostic MHT use on long-term survival of localized EOC.

Low-dose aspirin use and risk of ovarian cancer: a combined analysis from two nationwide studies in Denmark and Sweden.

BACKGROUND: Studies on association between low-dose aspirin use and ovarian cancer risk were mostly based on self-reported medication use and few had large enough sample size to investigate the potential modification effect by ovarian cancer risk factors. METHODS: In these two nationwide nested case-control studies among the Danish and Swedish female population, 11,874 women with ovarian cancer (30-84 years old) (Denmark: 7328 diagnosed in 2000-2019, Sweden: 4546 diagnosed in 2010-2018) were randomly age- matched with 473,960 female controls (293,120 from Denmark, and 181,840 from Sweden). We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) and combined the estimates based the fixed-effect assumption. Effect modification by inflammation-related risk factors and by indication (cardiovascular disease, CVD) were also investigated. RESULTS: Ever use of low-dose aspirin was not strongly associated with the overall risk of ovarian cancer (OR = 0.97; 95%CI: 0.92-1.03). However, the association differed according to parity (nulliparous: OR = 0.80, 95%CI: 0.70-0.92; parous: OR = 1.00, 95%CI: 0.94-1.07; p-interaction = 0.0024), and according to history of CVD (no CVD: OR = 0.91, 95%CI: 0.82-1.00; ever CVD: OR = 1.05, 95%CI: 0.97-1.13; p-interaction =0.0204). CONCLUSIONS: Low-dose aspirin use was associated with a decreased ovarian cancer risk especially in nulliparous women and in women without CVD diagnosis.

History of autoimmune disease and long-term survival of epithelial ovarian cancer: The extreme study.

OBJECTIVE: Patients with autoimmune disease may have impaired cancer survival. The aim was to investigate the association between autoimmune disease and ovarian cancer survival. METHODS: From the Extreme study, we included women diagnosed with epithelial ovarian cancer (EOC) in Denmark during 1990-2014 (n = 11,870). Information on exposure and covariates was retrieved from nationwide registries. Using pseudo-values, we estimated absolute and relative 5- and 10-year survival probabilities with 95% confidence intervals (CIs) for autoimmune diseases combined and for the four most common individual disorders in our study population, namely type 1 diabetes, rheumatoid arthritis, Graves' disease, and inflammatory bowel disease. RESULTS: The overall 5- and 10-year absolute survival probabilities were 35% and 24%, respectively, in women with EOC without autoimmune disease. Autoimmune diseases combined was not significantly associated with survival among women with EOC (5-year adjusted relative survival probability = 1.01, 95% CI: 0.94-1.09; 10-year adjusted relative survival probability = 0.90, 95% CI: 0.81-1.00). However, stratification by disease stage showed an impaired 10-year survival in women with autoimmune disease and a localized EOC (relative survival probability = 0.86, 95% CI: 0.76-0.97). None of the individual autoimmune diseases were statistically significantly associated with EOC survival. CONCLUSIONS: Only among women with localized EOC, there seemed to be a long-term survival loss associated with a history of autoimmune disease. In contrast, no significant association between a history of autoimmune disease and survival was observed in women with nonlocalized EOC where the survival is already low.

Risk of nonovarian cancer in a nationwide-based study of nearly 5000 women with borderline ovarian tumors in Denmark.

Evidence regarding cancer risk after borderline ovarian tumors (BOTs) is limited. We conducted a nationwide cohort study examining the incidence of nonovarian cancers in women with serous or mucinous BOTs compared with the general female population with up to 41 years of follow-up. Through the nationwide Pathology Registry, we identified nearly 5000 women with BOTs (2506 serous and 2493 mucinous) in Denmark, 1978 to 2018. We computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) as relative risk estimates of specific nonovarian cancers. Compared with general female population rates, women with serous BOTs had increased rates of particularly malignant melanoma (SIR = 1.9; 95% CI: 1.3-2.6), thyroid cancer (SIR = 3.0; 95% CI: 1.4-5.4) and myeloid leukemia (SIR = 3.2; 95% CI: 1.5-5.8), and women with mucinous BOTs had elevated rates of lung cancer (SIR = 1.7; 95% CI: 1.3-2.1), pancreatic cancer (SIR = 1.9; 95% CI: 1.2-2.9) and myeloid leukemia (SIR = 2.3; 95% CI: 0.9-4.7). We found no convincing association with neither breast nor colorectal cancer in women with BOTs. This is the first large nationwide study showing that women with specific types of BOTs have increased risks of several nonovarian cancers, likely due to some shared risk factors or genetic characteristics.

Long-term survival of nonlocalized epithelial ovarian cancer among women using menopausal hormone therapy prior to diagnosis: The extreme study.

Prediagnostic use of menopausal hormone therapy (MHT) has been suggested to be associated with improved survival of epithelial ovarian cancer (EOC). We investigated the potential long-term survival benefit of prediagnostic MHT use in women ≥50 years with nonlocalized EOC using the Extreme study including all women in Denmark registered with nonlocalized EOC during 2000 to 2014 (N = 3776). We obtained individual-level information on prediagnostic use of systemic estrogen therapy (ET) and estrogen plus progestin therapy (EPT) from the National Prescription Registry and estimated absolute and relative 5- and 10-year survival probabilities with 95% confidence intervals (CIs) using pseudo-values, taking into account histology, comorbidity, income and residual disease. Among women not having used prediagnostic MHT, 5- and 10-year absolute survival probabilities were 19% and 11%, respectively. Compared to MHT nonusers, prediagnostic systemic ET use for 3 to 4 years and ≥ 5 years was associated with 1.43 (95% CI: 1.01-2.02) and 1.22 (95% CI: 0.96-1.55) times higher 5-year survival probabilities, respectively. Ten-year survival probabilities were also increased but not statistically significantly. Among prediagnostic EPT users, increased 5-year (1.14, 95% CI: 0.85-1.53) and 10-year (1.38, 95% CI: 0.91-2.08) survival probabilities were observed after use for 3 to 4 years compared to MHT nonuse, whereas EPT use for ≥5 years was not associated with long-term survival of nonlocalized EOC. Our findings may suggest a better long-term survival of nonlocalized EOC in women having used long-term prediagnostic ET. However, the statistical precision of our results did not allow firm conclusions and more studies are needed.

Follow-up after abnormal cervical cancer screening in immigrants compared with Danish-born women - A nationwide register study.

Cervical cancer screening is offered free-of-charge to women aged 23-64 years in Denmark. Immigrants participate less in screening than Danish-born women, but little is known about their participation in follow-up after abnormal screening results. In this registry-based cohort study, we examined the likelihood of timely follow-up after an abnormal cervical cytology in immigrants from different countries and regions compared with Danish-born women. In nationwide registers, we identified women aged 23-64 years with high-grade (n = 74,335) or low-grade (n = 174,038) abnormal cytology during 1997-2017. Timely follow-up was defined as a new examination within six months for high-grade and 18 months for low-grade abnormalities. We calculated the probability of timely follow-up by country and region of origin and estimated odds ratios (ORs) of timely follow-up between immigrants and Danish-born women. The proportions with timely follow-up after high-grade abnormalities ranged from 90.6%-95.1% in immigrants from different countries or regions, compared with 95.5% in Danish-born women. For low-grade abnormalities, follow-up ranged from 75.2%-92.8% in immigrants, compared with 90.6% in Danish-born women. Women from Sub-Saharan Africa had low probability of timely follow-up after both high-grade (90.9%) and low-grade (75.2%) abnormalities. The differences between immigrants and Danish-born women remained when adjusting for age, year, income, employment and marital status. In conclusion, immigrants from most countries and regions were slightly less likely than Danish-born women to receive timely follow-up after abnormal cervical cytology, also after adjusting for socioeconomic differences. Efforts should be made to improve follow-up of abnormal screening results in immigrant groups with low attendance.

Prognostic impact of socioeconomic status on long-term survival of non-localized epithelial ovarian cancer ꟷ The Extreme study.

OBJECTIVE: To examine the influence of socioeconomic status (SES) on long-term survival of non-localized ovarian cancer. METHODS: All women in Denmark with a first diagnosis of non-localized epithelial ovarian cancer 1982-2007 were identified in the Cancer Registry and/or the Pathology Registry and followed up until December 2017. The survival probability was estimated after respectively 5 and 10 years, using so-called pseudo observations, and analyzed according to education, income, and marital status defined from nationwide registries. RESULTS: The study cohort included 6486 women, and the estimated 5- and 10-year survival probabilities were 21.4% and 12.7%, respectively. Compared to women with short education, the 5-year survival probability was 7% higher for women with medium (relative survival probability = 1.07, 95% CI: 0.97, 1.19) and long education (relative survival probability = 1.07, 95% CI: 0.93, 1.24). Compared with married women, the 5-year survival probability for divorced women/widower was slightly lower (0.85, 95% CI: 0.69, 1.04) and for unmarried women slightly higher (1.08, 95% CI: 0.94, 1.23). Finally, the probability of being alive 5 years after diagnosis was 1.09 times higher (95% CI: 0.95, 1.24) for medium-income women and 1.23 times higher (95% CI: 1.08, 1.41) for high-income women compared with low-income women. Similar patterns were observed for 10-year survival. CONCLUSIONS: Non-localized ovarian cancer patients have a poor prognosis. Our data suggest that among Danish women with advanced ovarian cancer, higher personal income is associated with slightly higher probability of long-term survival, whereas education and marital status did not affect the probability of long-term survival.

Risk of Anal High-grade Squamous Intraepithelial Lesions Among Renal Transplant Recipients Compared With Immunocompetent Controls.

BACKGROUND: Renal transplant recipients (RTRs) have increased risk of human papillomavirus (HPV)-related cancers, including anal cancer. We investigated the prevalence of anal high-grade intraepithelial lesions (HSILs) in RTRs compared with immunocompetent controls and risk factors for anal HSIL in RTRs. METHODS: We included 247 RTRs and 248 controls in this cross-sectional study. We obtained anal samples for HPV testing with INNO-LiPA and performed high-resolution anoscopy on all participants. The participants completed a questionnaire on lifestyle and sexual habits. We used logistic regression to estimate odds ratios (ORs) of histologically confirmed anal HSIL in RTRs vs controls and risk factors for anal HSIL in RTRs, stratified by sex and anal high-risk (hr) HPV status, adjusting for age, smoking, lifetime sexual partners, and receptive anal sex. RESULTS: RTRs had higher anal HSIL prevalence than controls, both among men (6.5% vs 0.8%; adjusted OR [aOR], 11.21 [95% confidence interval {CI}, 1.46-291.17]) and women (15.4% vs 4.0%; aOR, 6.41 [95% CI, 2.14-24.10]). Among those with anal hrHPV, RTRs had higher anal HSIL prevalence than controls (33.8% vs 9.5%; aOR, 6.06 [95% CI, 2.16-20.27]). Having had receptive anal sex (aOR, 6.23 [95% CI, 2.23-19.08]) or genital warts (aOR, 4.21 [95% CI, 1.53-11.48]) were risk factors for anal HSIL in RTRs. All HSIL cases occurred in individuals with anal hrHPV. CONCLUSIONS: RTRs had increased risk of anal HSIL compared with immunocompetent controls, with particularly high prevalence in female RTRs. Receptive anal sex, previous genital warts, and anal hrHPV infection were risk factors for anal HSIL in RTRs. Screening for anal HSIL in RTRs should be considered. CLINICAL TRIALS REGISTRATION: NCT03018927.

Non-participation in cervical cancer screening according to health, lifestyle and sexual behavior: A population-based study of nearly 15,000 Danish women aged 23-45 years.

High participation in cervical cancer screening is essential for an effective screening program. In this population-based study, we investigated associations between general health, lifestyle and sexual behavior, and non-participation in cervical cancer screening in Denmark. During 2011-2012, a random sample of women aged 18-45 years from the general female population were invited to participate in a survey regarding health, lifestyle and sexual habits. Altogether 18,631 women responded (response rate: 75.1%), of whom 14,271 women aged 23-45 years were included in this analysis. Information on screening participation within four years after response, and data on sociodemographic characteristics, was obtained from nationwide registers. Logistic regression was used to calculate odds ratios (ORs) for non-participation, crude and adjusted for sociodemographic characteristics. Overall, 13.9% of the women were not screened during follow-up. The odds of non-participation was increased in women who were overweight (ORadj. = 1.20; 95% CI, 1.06-1.35), obese (ORadj. = 1.46; 95% CI, 1.27-1.67), perceived themselves as much too fat (ORadj. = 1.50; 95% CI, 1.29-1.74), had poor self-perceived health (ORadj. = 1.22; 95% CI, 1.03-1.45) or smoked daily (ORadj. = 1.81; 95% CI, 1.61-2.03). Conversely, women with previous genital warts or other sexually transmitted infections, and young women with ≥10 lifetime sexual partners or ≥2 new recent partners, had decreased odds of non-participation. In conclusion, obesity, poor self-perceived health and daily smoking were associated with lower participation in cervical cancer screening. Interventions targeting these groups are needed.

Human papillomavirus vaccination in immigrants and descendants of immigrants in Denmark.

OBJECTIVE: In Denmark, human papillomavirus (HPV) vaccination has been offered at age of 12 to girls born in 1996 and later. In this cohort study, we examined routine HPV vaccination uptake in immigrants and descendants from different countries and regions compared with native Danes, including the influence of socioeconomic characteristics and potential changes in uptake by birth cohort. METHODS: In nationwide registers, we identified all girls born in 1996-2003 (n = 260 251) and obtained information on country of origin, HPV vaccinations and parents' income and employment. Vaccination was defined as receiving ≥1 dose within 2 years after eligibility for routine vaccination. Odds ratios (ORs) were estimated by logistic regression separately for birth cohorts 1996-2000 and 2001-2003. RESULTS: Uptake in immigrants and descendants varied by country and region of origin. Overall, immigrants had lower uptake than native Danes, in birth cohorts 1996-2000 [79% vs. 93%, OR = 0.31; 95% confidence interval (CI), 0.29-0.34] and 2001-2003 (63% vs. 73%, OR = 0.60; 95% CI, 0.54-0.66). Descendants had lower uptake than native Danes in cohorts 1996-2000 (89% vs. 93%, OR = 0.65; 95% CI, 0.60-0.68), but higher uptake in cohorts 2001-2003 (76% vs. 73%, OR = 1.15; 95% CI, 1.08-1.21). Most associations were attenuated, but not entirely explained, when adjusting for socioeconomic characteristics. CONCLUSION: HPV vaccination uptake varied by country and region. Most immigrants had lower uptake than native Danes, and in most groups, this was not fully explained by socioeconomic differences. Patterns in descendants were mixed. Interventions to increase uptake should be tailored to specific groups of immigrants/descendants.

Risk of primary brain tumour after breast cancer.

INTRODUCTION: Cancer registry data in the USA indicated that women diagnosed with breast cancer before the age of 40 were at increased risk of a new primary tumour within the brain and women aged 50 years or above were at lower risk than expected. Our aim was to investigate if similar results could be found in Danish population-based data, considering an explanatory role of hormonal status. METHODS: Our study cohort included all women diagnosed with breast cancer below the age of 60 between 1978 and 2013 in Denmark. A total of 47,920 women were followed up in the Danish Cancer Registry for primary brain cancer. Standardized incidence ratios (observed/expected cases (O/E)) were used to estimate the risk of getting a primary brain tumour in the breast cancer cohort. RESULTS: Data indicated an increased tendency of brain cancer following breast cancer at ages below 60 years (O/E = 1.24). For premenopausal women (age <49 at the diagnosis of breast cancer) the O/E was 1.25. Stratifying by time of breast cancer diagnosis, we observed an increased risk of being diagnosed with a brain tumour among women aged 49 years or younger at breast cancer diagnosis between 2004 and 2013. CONCLUSION: The results indicate an increased tendency of developing a primary brain tumour in women with previous breast cancer history. Whereas the finding in premenopausal women is in line with the SEER data, the finding among postmenopausal is not. Primary brain tumours in breast cancer patients call for research in genetics and hormones to establish common risk factors.

Participation in cervical cancer screening among immigrants and Danish-born women in Denmark.

In this nationwide register-based cohort study, we examined cervical cancer screening participation among immigrants in Denmark by country and region of origin. Furthermore, we assessed whether differences in screening participation between immigrants and Danish-born women were explained by sociodemographic or health-related characteristics, and examined predictors of participation among immigrants. Using high-quality registries, we identified women invited for cervical cancer screening during 2008-2009 and retrieved individual-level data on sociodemographic-, health- and immigration-related characteristics. A total of 610,907 women were followed for up to 2.9 years after screening invitation. We estimated the probability of participation using the Aalen-Johansen estimator and the hazard ratios (HRs) of participation using Cox regression. The probability of participation within follow-up was 74.5% (95% CI, 74.4%-74.6%) in Danish-born women; 61.2% (95% CI, 60.4%-62.1%) in Western immigrants; and 61.3% (95% CI, 60.9%-61.8%) in non-Western immigrants. Participation in immigrants varied by region of origin from 44.3% (95% CI, 41.4%-47.4%) in immigrants from North America, New Zealand and Australia to 67.8% (95% CI, 65.4%-70.3%) in immigrants from South- and Central America. Substantial variation was seen between specific countries of origin. Differences in participation between immigrants and Danish-born women were not explained by sociodemographic or health-related characteristics. Predictors of low participation in immigrants included lower income, unemployment, being unmarried, having a history of schizophrenia or other psychoses, and ≤5 years' stay in Denmark. In conclusion, cervical cancer screening participation in immigrants varied by region and country of origin, but all immigrant groups had lower participation than Danish-born women.

Determinants for Participation in Human Papillomavirus Self-Sampling among Nonattenders to Cervical Cancer Screening in Denmark.

Background: Offering human papillomavirus-based self-sampling to nonparticipants in routine cervical cancer screening can increase screening participation. However, little is known about characteristics of women who accept self-sampling. In this population-based study, we investigated determinants for participation in self-sampling among Danish nonattenders to routine cervical cancer screening.Methods: During 2014 to 2015, a random sample of screening nonparticipants ages 27 to 65 years living in the Capital Region of Denmark were invited for self-sampling. Of 21,314 eligible women, 4,743 participated in self-sampling. Information on sociodemographic characteristics and mental and physical health of all the women was obtained from nationwide registries, and 3,707 women completed a questionnaire on lifestyle, sexual behavior, and reasons for nonparticipation in routine screening. We used logistic regression to estimate ORs for participation in self-sampling, crude, and adjusted for sociodemographic characteristics.Results: Basic education [ORadjusted = 0.79; 95% confidence interval (CI), 0.72-0.88], low income (ORadjusted = 0.66; 95% CI, 0.59-0.73), origin from a nonwestern country (ORadjusted = 0.43; 95% CI, 0.38-0.48), and being unmarried (ORadjusted = 0.66; 95% CI, 0.61-0.72) were associated with lower self-sampling participation. Long-term unscreened women (ORadjusted = 0.49; 95% CI, 0.45-0.53), women with prior schizophrenia or other psychoses (ORadjusted = 0.62; 95% CI, 0.48-0.80), women with poor self-perceived health (ORadjusted = 0.42; 95% CI, 0.25-0.69), and women who perceived screening as unnecessary (ORadjusted = 0.54; 95% CI, 0.37-0.80) or irrelevant (ORadjusted = 0.81; 95% CI, 0.78-0.96) were less likely to self-sample.Conclusions: Certain population groups, including women with low socioeconomic position or of nonwestern origin, were less likely to participate in self-sampling.Impact: Targeted approaches may be needed to increase screening participation in these groups. Cancer Epidemiol Biomarkers Prev; 27(11); 1342-51. ©2018 AACR.

Can group-based reassuring information alter low back pain behavior? A cluster-randomized controlled trial.

BACKGROUND: Low back pain (LBP) is common in the population and multifactorial in nature, often involving negative consequences. Reassuring information to improve coping is recommended for reducing the negative consequences of LBP. Adding a simple non-threatening explanation for the pain (temporary muscular dysfunction) has been successful at altering beliefs and behavior when delivered with other intervention elements. This study investigates the isolated effect of this specific information on future occupational behavior outcomes when delivered to the workforce. DESIGN: A cluster-randomized controlled trial. METHODS: Publically employed workers (n = 505) from 11 Danish municipality centers were randomized at center-level (cluster) to either intervention (two 1-hour group-based talks at the workplace) or control. The talks provided reassuring information together with a simple non-threatening explanation for LBP-the 'functional-disturbance'-model. Data collections took place monthly over a 1-year period using text message tracking (SMS). Primary outcomes were self-reported days of cutting down usual activities and work participation. Secondary outcomes were self-reported back beliefs, work ability, number of healthcare visits, bothersomeness, restricted activity, use of pain medication, and sadness/depression. RESULTS: There was no between-group difference in the development of LBP during follow-up. Cumulative logistic regression analyses showed no between-group difference on days of cutting down activities, but increased odds for more days of work participation in the intervention group (OR = 1.83 95% CI: 1.08-3.12). Furthermore, the intervention group was more likely to report: higher work ability, reduced visits to healthcare professionals, lower bothersomeness, lower levels of sadness/depression, and positive back beliefs. CONCLUSION: Reassuring information involving a simple non-threatening explanation for LBP significantly increased the odds for days of work participation and higher work ability among workers who went on to experience LBP during the 12-month follow-up. Our results confirm the potential for public-health education for LBP, and add to the discussion of simple versus multidisciplinary interventions.

The diagnostic impact of testicular biopsies for intratubular germ cell neoplasia in cryptorchid boys and the subsequent risk of testicular cancer in men with prepubertal surgery for syndromic or non-syndromic cryptorchidism.

INTRODUCTION: Cryptorchidism is a risk factor for testicular cancer in adult life. It remains unclear how prepubertal surgery for cryptorchidism impacts later development of adult testicular cancer. The aim of study was to investigate tools to identify the cryptorchid boys who later develop testicular cancer. METHODS: The study cohort consisted of 1403 men operated prepubertally/pubertally for undescended testis between 1971 and 2003. At surgery testicular biopsies were taken from the cryptorchid testes. The boys were followed for occurrence of testicular cancer. The testicular cancer risk was compared to the risk in the Danish Population. Testicular biopsies from the boys who developed testicular cancer during follow-up underwent histological examination with specific diagnostic immunohistochemical markers for germ cell neoplasia. RESULTS: The cohort was followed for 33,627 person years at risk. We identified 16 cases with testicular cancer in adulthood. The standardized incidence ratio was 2.66 (95% CI: 1.52-4.32). At time of primary surgery in prepubertal/pubertal age Intratubular Germ Cell Neoplasia (ITGCN) was diagnosed in 5 cases and the boys were unilaterally orchiectomized. At follow-up new immunohistochemical staining indicated ITGCN in two of the 16 cancer cases at reevaluation of the original biopsies from time of prepubertal/pubertal surgery. One had syndromic cryptorchid and developed seminoma, and another showed nonsyndromic cryptorchidism and developed embryonic teratocarcinoma. Totally, ITGCN was diagnosed in 0.5% (7/1403) of prepubertal cryptorchid boys, whereof 57% (4/7) in syndromic-cryptorchidism. DISCUSSION: ITGCN is predominantly observed prepubertally in boys with syndromic-cryptorchidism. In nonsyndromic cryptorchidism testicular cancer develops postpubertally, generally not based on dormant germ cells of ITGCN caused by an early fetal maldevelopment. LEVELS OF EVIDENCE: LEVEL I.

Do X-ray-occult fractures play a role in chronic pain following a whiplash injury?

PURPOSE: Whiplash trauma in motor vehicle accidents (MVA) may involve various painful soft tissue damages, but weeks/months later a minority of victims still suffers from various long-lasting and disabling symptoms, whiplash-associated disorders (WAD). The etiology is currently unknown, but X-ray-occult fractures may be one cause in some cases. The purpose of this prospective study was to examine the association between occult fractures, as seen on bone single photon emission computed tomography (SPECT), with neck-, head- and arm pain. METHODS: An inception cohort of 107 patients presenting with acute whiplash symptoms following an MVA was invited to have a cervical SPECT shortly post injury and again 6 months later. Associations between occult fractures and pain levels at baseline, 6 and 12 months of follow-up were analyzed. RESULTS: Eighty-eight patients had baseline SPECT performed at median 15 days (range 3-28) post injury, but only 49 patients accepted to have the follow-up SPECT at 6 months. Abnormal SPECT, defined as minimum one area of focal uptake, was seen in 32 patients at baseline, reflecting an occult fracture. Occult fractures were not associated with pain levels, neither at baseline nor at follow-up. CONCLUSION: Occult fractures do not seem to play a role for development of chronic pain after whiplash.