Incidence and clearance of cervical and anal high-risk human papillomavirus in kidney transplant recipients: Results from a Danish prospective clinical study.

This study investigates the incidence and clearance of cervical and anal high-risk human papillomavirus (hrHPV) infection in kidney transplant recipients (KTRs) compared to immunocompetent controls. During 2016-2017, we enrolled 125 female KTRs and 125 female controls. Liquid-based cervical and anal cytology samples collected at enrollment and follow-up were tested for human papillomavirus (HPV) DNA using the CLART HPV2 test. All participants answered a questionnaire on lifestyle and sexual behavior at both examinations. KTRs had an increased age-adjusted risk of incident cervical hrHPV infection compared to controls (hazard ratio [HR] = 3.6, 95% CI = 1.2-11.2). Probability of cervical hrHPV clearance at 18 months was lower among KTRs (8.3%) than controls (66.7%). There was no statistically significant difference in anal hrHPV incidence between KTRs and controls (HR = 0.9, 95% CI = 0.4-2.0). Clearance of anal hrHPV was similar between KTRs and controls at 18 months. During the total follow-up, a lower anal hrHPV clearance, although not statistically significant, was observed among KTRs (HR = 0.3, 95% CI = 0.06-1.2). KTRs had higher incidence of cervical hrHPV and lower probability of clearance, especially of cervical hrHPV infections, than controls. Our findings support that KTRs are at increased risk of HPV infection and point to the need for targeted HPV prevention strategies, such as cervical cancer screening.

Anal Human Papillomavirus Infection in Kidney Transplant Recipients Compared With Immunocompetent Controls.

BACKGROUND: Kidney transplant recipients (KTRs) have increased risk of human papillomavirus (HPV)-related anogenital (pre)cancers, including anal high-grade intraepithelial lesions and cancer. Previous studies on anal high-risk HPV (hrHPV) among KTRs are sparse. METHODS: In a cross-sectional study, we included 247 KTRs and 248 controls from a dermatology department and 5 nephrology departments in Denmark during 2016-2017. All participants provided an anal cytobrush sample that was tested for HPV DNA. Participants completed a questionnaire on lifestyle and sexual habits. We used logistic regression to estimate odds ratios (ORs) of anal hrHPV in KTRs compared with controls and risk factors for anal hrHPV in KTRs. RESULTS: The anal hrHPV prevalence was higher in female KTRs (45.5%) than in controls (27.2%). Female KTRs had almost 3-fold higher adjusted odds of anal hrHPV than controls (adjusted OR, 2.87 [95% confidence interval, 1.57-5.22]). In contrast, among men we did not observe increased prevalence or odds of anal hrHPV in KTRs compared with controls (prevalence, 19.4% vs 23.6%; adjusted OR, 0.85 [95% 95% confidence interval, .44-1.64]). Among hrHPV-positive KTRs, 63% and 52% of men and women, respectively, were infected with hrHPV types covered by the nonavalent HPV vaccine (type 16, 18, 31, 33, 45, 52, or 58). Current smoking, >10 lifetime sexual partners, history of genital warts, and among men having had receptive anal sex were risk factors for anal hrHPV in KTRs. CONCLUSIONS: Female KTRs had an increased risk of anal hrHPV compared with immunocompetent controls. Our findings indicate that pretransplant HPV vaccination should be considered to prevent anal high-grade intraepithelial lesions and cancer caused by anal hrHPV infection in KTRs. CLINICAL TRIALS REGISTRATION: NCT03018327.

Clinical Importance of Superior Sensitivity of the Aptima TMA-Based Assays for Mycoplasma genitalium Detection.

Mycoplasma genitalium (MG) is a common cause of nongonococcal cervicitis and urethritis. We investigated the demographic and clinical characteristics of patients tested in Denmark with the Conformité Européenne (CE)/in vitro diagnostics (IVD) Aptima Mycoplasma genitalium assay (CE/IVD AMG; Hologic) and examined the clinical significance of the higher sensitivity of the TMA-based MG assays. From March to June 2016, urogenital and extragenital specimens from consecutive attendees at a sexually transmitted infection clinic in Copenhagen, Denmark were tested with the CE/IVD AMG assay (TMA-based), the research-use-only MG Alt TMA-1 assay (Hologic), a laboratory-developed TaqMan mgpB quantitative real-time PCR (qPCR), and the Aptima Combo 2 (CT/NG; Hologic). Demographic characteristics and clinical symptoms were collected from the patient records. There were 1,245 patients included in the study. The MG prevalence among female subjects was 9.4%, and the MG prevalence among male subjects was 8.7%. Compared to the TMA-based assays, the sensitivity of the PCR-based MG assay was 64.52%, and 55 specimens from 48 individuals were missed in the mgpB qPCR. Of these, 26 individuals (54.2%) were symptomatic, whereas, among 64 individuals with concordant results, 30 individuals (46.9%) were symptomatic; no statistically significant difference was found between the groups (P = 0.567). The improved sensitivity of the TMA-based assays resulted in diagnoses of more patients with clinically relevant symptoms for which antibiotic treatment is indicated. However, approximately half of the MG-infected patients reported no symptoms, and future research is needed to investigate the pros and cons of diagnosing and treating MG in asymptomatic subjects.

Risk of genital warts in renal transplant recipients-A registry-based, prospective cohort study.

Genital warts (GWs) are a risk factor for subsequent human papillomavirus (HPV)-related anogenital cancers. In this register-based, prospective cohort study, we estimated the risk of GWs in renal transplant recipients (RTRs) compared with a nontransplanted cohort. In a nationwide database, we identified first-time RTRs in Denmark during 1996 to 2015. For each RTR, 50 age- and sex-matched nontransplanted individuals were selected from the population registry. Information on GWs, sociodemographic characteristics, HPV vaccination, and other causes of immunosuppression was retrieved from registries. We estimated the cumulative incidence of GWs and used Cox regression to estimate hazard ratios (HR) of GWs in RTRs vs non-RTRs. We included 3268 RTRs and 162 910 non-RTRs without GWs 1 year before baseline. RTRs had higher hazard of GWs than non-RTRs (HR = 3.30; 95% confidence interval, 2.76-3.93, adjusted for sex, age, education, and income). The increased hazard of GWs compared with non-RTRs was more pronounced in female than in male RTRs. Although not statistically significant, the hazard tended to be higher in RTRs with functioning grafts compared with RTRs on dialysis after graft failure. The hazard of GWs was increased <1 year after transplantation and remained increased during ≥10 years. In conclusion, RTRs had substantially higher risk of GWs than non-RTRs.

Multidrug-resistant Neisseria gonorrhoeae infection with ceftriaxone resistance and intermediate resistance to azithromycin, Denmark, 2017.

We describe a multidrug-resistant Neisseria gonorrhoeae infection with ceftriaxone resistance and azithromycin intermediate resistance in a heterosexual man in Denmark, 2017. Whole genome sequencing of the strain GK124 identified MSLT ST1903, NG-MAST ST1614 and all relevant resistance determinants including similar penA resistance mutations previously described in ceftriaxone-resistant gonococcal strains. Although treatment with ceftriaxone 0.5 g plus azithromycin 2 g was successful, increased awareness of spread of gonococcal strains threatening the recommended dual therapy is crucial.

Molecular Typing of Treponema pallidum in Denmark: A Nationwide Study of Syphilis.

The aim of this nationwide study is to determine the strain type diversity among patients diagnosed with syphilis by PCR during a 4-year period in Denmark. Epidemiological data, including HIV status, for all patients were obtained from the Danish national syphilis registration system. Molecular strain typing was based on characterization of 3 variable treponemal genes, arp, tpr and tp0548. A total of 278 specimens from 269 patients were included. Among the fully typeable specimens (n = 197), 22 strain types were identified, with 1 type, 14d/g, accounting for 54%. The majority (93%) of the patients reported acquiring syphilis in Denmark. Among patients with concurrent HIV, 9 full strain types were identified and no difference in strain type was found by HIV status (p = 0.197). In conclusion, the majority of patients were infected in Denmark and the HIV-infected syphilis patients were diagnosed with a wide spectrum of different strain types of Treponema pallidum.

High-resolution anoscopy can diagnose precursors to anal cancer.

Anal cancer risk is increased in certain risk groups including people living with HIV (PLWH), especially in men who have sex with men, but also in organ transplant recipients and women with a history of cervical or vulva dysplasia or cancer. High-resolution anoscopy (HRA) is a tool to diagnose anal high-grade squamous intraepithelial lesions (HSIL), and HRA-guided treatment of anal HSIL has been shown to reduce the risk of anal cancer in PLWH. The purpose of this review is to increase the awareness of HRA but also of tertiary prevention by digital anal rectal examination.

Genital and extra-genital screening for gonorrhoea using the BD Probetec ET system with an in-house PCR method targeting the porA pseudogene as confirmatory test.

Diagnosing gonorrhoea from extra-genital as well as genital sites is important in managing this sexually transmitted disease. In this study we evaluated a screening procedure for Neisseria gonorrhoeae (GC) from all sample sites in a low-prevalence setting. A total of 69,252 specimens submitted for Chlamydia trachomatis testing were also examined for GC on the BD Viper™ platform using the BD Probetec ET system. In order to avoid false-positive results all GC BD reactive samples were re-tested using a PCR method with the porA pseudogene as target. Using this method we screened 170% more samples for GC than in the previous year, in the same population, and diagnosed more than twice as many GC-positive episodes. The BD system can be used successfully to screen extra-genital as well as genital specimen types for GC in a low-prevalence area if it is combined with a validated confirmatory PCR test.

Incidence and cost of anal, penile, vaginal and vulvar cancer in Denmark.

BACKGROUND: Besides being a causative agent for genital warts and cervical cancer, human papillomavirus (HPV) contributes to 40-85% of cases of anal, penile, vaginal and vulvar cancer and precancerous lesions. HPV types 16 & 18 in particular contribute to 74-93% of these cases. Overall the number of new cases of these four cancers may be relatively high implying notable health care cost to society. The aim of this study was to estimate the incidence and the health care sector costs of anal, penile, vaginal and vulvar cancer. METHODS: New anogenital cancer patients were identified from the Danish National Cancer Register using ICD-10 diagnosis codes. Resource use in the health care sector was estimated for the year prior to diagnosis, and for the first, second and third years after diagnosis. Hospital resource use was defined in terms of registered hospital contacts, using DRG (Diagnosis Related Groups) and DAGS (Danish Outpatient Groups System) charges as cost estimates for inpatient and outpatient contacts, respectively. Health care consumption by cancer patients diagnosed in 2004-2007 was compared with that by an age- and sex-matched cohort without cancer. Hospital costs attributable to four anogenital cancers were estimated using regression analysis. RESULTS: The annual incidence of anal cancer in Denmark is 1.9 per 100,000 persons. The corresponding incidence rates for penile, vaginal and vulvar cancer are 1.7, 0.9 and 3.6 per 100,000 males/females, respectively. The total number of new cases of these four cancers in Denmark is about 270 per year. In comparison, the total number of new cases cervical cancer is around 390 per year. The total cost of anogenital cancer to the hospital sector was estimated to be 7.6 million Euros per year. Costs associated with anal and vulvar cancer constituted the majority of the costs. CONCLUSIONS: Anogenital cancer incurs considerable costs to the Danish hospital sector. It is expected that the current HPV vaccination program will markedly reduce this burden.

[Neurosyphilis].

This review focuses on typical and atypical manifestations of neurosyphilis. The manifestations of neurosyphilis are manyfold and may involve many specialties. Today, clinicians have limited experience with the well-described manifestations of neurosyphilis. Many screening opportunities for men who have sex with men might catch the majority of cases of syphilis in this group. However, a concern could be if disclosure about heterosexuality or, in general, monosymptomatic neurosyphilis constitute a risk for delayed diagnosis.

[Ano-genital warts are more than benign lesions].

Ano-genital warts are in general considered as benign lesions, as they are mostly caused by the non-oncogenic HPV types 6 and 11. In this review, there is a focus on the problematic issues, that these lesions and their treatments can cause. Both topical and ablative treatments are associated with side effects, and the varying effect of the treatments combined with an uncertain timeline to clearance are known to cause psychological distress. Vaccination against HPV-6 and -11 has been shown to reduce the incidence of this troublesome infection substantially in both women and men in countries with high vaccine coverage.

[Herpes simplex virus type 1 in a patient with herpes zoster]. / Herpes simplex-virus type 1 påvist hos patient med herpes zoster.

In this case report we present an otherwise healthy 63 year-old male patient with herpes zoster corresponding to the 2nd left branch of the trigeminal nerve. Real time-polymerase chain reaction analyses were positive for both herpes simplex virus (HSV) type 1 and varicella zoster virus (VZV). The most probable explanation is that this reflects asymptomatic, latent expression of HSV-1 in a herpes zoster patient with no clinical relevance. Another hypothesis is that reactivation of a neurotropic herpes virus can reactivate another neurotropic virus if both types are present in the same ganglion. If co-infection with HSV/VZV is suspected the treatment regimen for herpes zoster will sufficiently treat a possible HSV infection also.

[The quality of life of male homosexual patients with condyloma]. / Livskvalitet hos homoseksuelle maend med kondylomer.

INTRODUCTION: A recent qualitative study shows that genital warts can reduce the quality of life of heterosexual patients considerably. This follow-up study seeks to elucidate the illness perception among men who have sex with men (MSM). The aim is to examine the extent to which minority cultural conditions and factors affect the experiences of these patients. MATERIAL AND METHODS: This study was based on qualitative interviews with six Danish MSM. Along with the study among heterosexual patients, a literature review identified the important questions to be presented to the participants. RESULTS: Many MSM worry about being stigmatized in the homosexual "scene" and thereby losing their affiliation to a significant social group as well as their chances of finding sex and love. Most participants had suffered from genital warts for several years - which added to the negative psycho-sexual and social effects of the disease. These participants' fears of developing anal cancer corresponded to the concerns of female genital warts patients about cervical cancer. CONCLUSION: Ano-genital HPV infection is common among MSM. However, these men will not benefit to the same extent as heterosexual men from the herd immunity effect of HPV vaccination of girls. MSM may have particular pathological pictures as well as concerns that should be addressed when communicating with these patients and taken into account when considering HPV vaccination of boys.

[Diagnostics and treatment of pruritus ani]. / Diagnostik og behandling af pruritus ani.

Pruritus ani is defined as an intense itching sensation affecting the perianal skin. The condition affects up to 5% of the population, and occurs four times more commonly in men than in women. Pruritus ani occurs in a primary form caused by overt but insufficient cleansing of the perianal skin, and in a secondary form caused by underlying pathology, often of proctological or dermatological/infectious origin. Causes and treatment are reviewed, and it is concluded that the condition, even in its chronic refractory form, has a favourable prognosis.

[Quality of life of patients with condyloma]. / Kondylompatienters livskvalitet.

INTRODUCTION: The new quadrivalent vaccine against human papillomavirus (HPV) can prevent a large number of cervical cancer cases and most cases of genital warts. Genital warts are among the most common sexually transmitted diseases in Denmark and constitute a considerable burden to the health care system as well as to the individual patient. The aim of this study is to examine the ways in which genital warts may affect the patient's quality of life. The results are important in relation to treatment as well as counselling of patients suffering from genital warts. The results are particularly relevant to decisions concerning the introduction of HPV vaccination of men as well as women. MATERIAL AND METHODS: A qualitative research design was applied using focus group interviews with male and female genital wart patients aged 18-30 years. The study was based on a literature review which identified the important issues and questions presented to the participants. RESULTS: The participants in the study have a significantly lowered quality of life due to their genital warts. The disease negatively affects them psychologically, socially and in their sex and love life in particular. The course of treatment is a burden because of the uncertain time-line and the varying effectiveness. There is much need for more information and communication about the disease and its psycho-sexual aspects. CONCLUSION: The development of a quadrivalent HPV vaccine is a milestone in the prevention of both cervical cancer and genital warts. The knowledge of genital warts is limited despite the prevalence of the disease and its severe effects on the patient's quality of life. This study indicates that HPV vaccination of both sexes would have a marked positive effect on the mental burden associated with the disease.

[Impotence caused by Methotrexate treatment]. / Impotens forårsaget af behandling med methotrexat.

Methotrexate (MTX) is used in the treatment of malignant and non-malignant diseases. This case report describes impotence as a seldom but possible overlooked adverse effect to MTX treatment. A 58 year-old man was treated for erythrodermia with a weekly dose of 7.5 mg MTX. He developed erective impotence nine months after initiation of treatment. Two weeks after discontinuation of MTX the impotence subsided, but when MTX treatment was reintroduced, the impotence returned after two months. Only a few other cases of impotence associated with MTX have been described previously.