[HPV vaccines effective and safe]. / HPV-vacciner effektiva och säkra.

In this review we summarize the current knowledge about the HPV vaccines developed in the beginning of the 21st century. The vaccines are very effective and safe, with no serious side effects. In Sweden we have a school-based prophylactic vaccination programme for both girls and boys. To this age group, we offer two doses of the nonavalent vaccine. The main purpose of the vaccination is to decrease the rate of genital cancer and its precursor lesions. This has mainly been studied for the cervix, which is the locus for the most important HPV-related cancer. Among other HPV 16-related malignancies that can be prevented by the vaccine is anal cancer. Genital warts are a challenging benign condition difficult to treat, often associated with psychosexual consequences. In Sweden we already have seen a decrease of HPV infection, genital warts, precancerous cervical lesions and cervical cancer.

The bacterial microbiota in first-void urine from men with and without idiopathic urethritis.

BACKGROUND: Non-gonococcal urethritis (NGU) is a common syndrome in men. NGU may have several causes, but many cases are caused by sexually transmitted infections that may also cause complications in their female partners. Chlamydia trachomatis and Mycoplasma genitalium are the most common causes of NGU, but in up to 35% of the cases, none of the known viral or bacterial causes are found. Traditionally, pathogens have been detected using various culture techniques that may not identify all species present in the urethra. To address this, we used culture-independent methods for analysis of the male urethral microbiota. METHODS: This case-control study analysed first void urine samples, collected at STD clinics in Stockholm, Sweden from men with idiopathic urethritis (IU), i.e. negative for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Ureaplasma urealyticum, Trichomonas vaginalis, adenovirus, and herpes simplex virus type 1 and -2 together with samples from men without urethritis. Forty-six controls and 39 idiopathic urethritis patients were analysed. RESULTS: The microbiota was highly diverse: None of the 302 operational taxonomic units (OTUs) found in negative controls and IU patients were found in all of the samples or even in all of the samples in one group. More than 50% of the OTUs were only found in one or two of the total of 85 samples. Still the most dominant 1/6 of the genera constituted 79% of the sequences. Hierarchical clustering in a heatmap showed no specific clustering of patients or controls. A number of IU patient samples were dominated by a single genus previously related to urethritis (Gardnerella, Haemophilus, Ureaplasma). CONCLUSION: The male urethra contain a very diverse composition of bacteria, even in healthy controls. NGU may be caused by a number of different bacteria but more studies including a higher number of samples are needed for elucidation of the role of each species.

Herpes simplex virus specific T cell response in a cohort with primary genital infection correlates inversely with frequency of subsequent recurrences.

OBJECTIVES: During the last decades, a changing epidemiological pattern of genital herpes simplex virus (HSV) infection has emerged. Primary infection is now caused as often by HSV-1 as by HSV-2. Once established, HSV can be reactivated leading to recurrent mucocutaneous lesions as well as meningitis. Why some otherwise immune-competent individuals experience severe and frequent recurrences is not known, and the immunological mechanism underlying recurrent symptomatic HSV infection is not fully understood. In this study, we investigate and characterise the immune response of patients with first episode of HSV genital infection and its relation to the frequency of symptomatic recurrences. METHODS: In this cohort study, clinical and immunological data were collected from 29 patients who were followed 1 year after presenting with a first episode of genital or meningeal HSV infection. They were classified by PCR and serology as those with primary HSV-1, primary HSV-2 and non-primary HSV-2 infection. RESULTS: HSV-specific interleukin(Il)-4 and Il-10 responses at first visit were higher in primary infected HSV-2 infected patients experiencing lower numbers of recurrences during subsequent year. CONCLUSIONS: The median number of recurrences following primary HSV-2 genital infection may partly be predicted by the strength of an early HSV-specific IL-4 and IL-10 response.

Urethritis-associated Pathogens in Urine from Men with Non-gonococcal Urethritis: A Case-control Study.

The aetiology of non-gonococcal urethritis (NGU) remains unexplained in 30-40% of patients. Urine samples from men attending Swedish sexually transmitted disease clinics were examined by species-specific quantitative PCRs for Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, Ureaplasma urealyticum, U. parvum, adenovirus, herpes simplex virus, Neisseria meningitidis, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae. A total of 187 men with acute NGU (symptoms ≤ 30 days) and 24 with chronic NGU (symptoms < 30 days) were cases, and 73 men without NGU were controls. Number of lifetime sexual partners was negatively associated with U. urealyticum bacterial load. C. trachomatis and M. genitalium were associated with NGU, as was U. urealyticum, with bacterial loads ≥ 1.3 × 103 genome equivalents/ml urine. Virus and H. influenzae might explain a few NGU cases, but the aetiology in at least 24% of patients with acute NGU was unexplained. In multivariate analysis, detection of U. urealyticum was significantly more common in acute NGU (20%) compared with controls (11%).

Evaluation of human papillomavirus DNA detection in samples obtained for routine Chlamydia trachomatis screening.

BACKGROUND: The costs and logistics involved in obtaining samples is a bottleneck in large-scale studies of the circulation of human papillomavirus (HPV), which are useful for monitoring and optimisation of HPV-vaccination programs. Residual samples obtained after screening for Chlamydia trachomatis could constitute a convenient, low-cost solution. OBJECTIVES: We evaluated HPV DNA detection and typing using (i) the residual samples routinely taken for C. trachomatis screening or (ii) the sample types used in large-scale phase III HPV vaccination trials (cervical, vulvar, labial, perineal, perianal, scrotal and penile shaft samples). STUDY DESIGN: Samples from 127 men and 110 women attending two sexual health clinics were analysed using PCR for HPV DNA, with typing using mass spectrometry. RESULTS: The HPV DNA prevalence was 7.1% in male urine samples, but 57.3% in female urine/vaginal samples, which was even higher than the HPV prevalence found in cervical samples (54.1%). The sensitivity for HPV DNA detection in the urine/vaginal samples was 7.9% (95% CI 3.0-16.4) for men and 78.9% (95% CI 67.6-87.7) for women, using detection in any one of the reference samples as reference. With cervical samples as reference, the sensitivity was 89.3 % (95% CI 78.1-95.9). CONCLUSIONS: Among men, low sensitivity of urine for HPV detection suggests limited usefulness. Among women, the high sensitivity of urine/vaginal samples for HPV detection suggests a useful low-cost solution for the study of HPV epidemiology.

Human papillomavirus-associated balanoposthitis--a marker for penile intraepithelial neoplasia?

The purpose of this study was to analyse, among men treated with diathermy, whether there was a difference in balanoposthitis between men with histopathologically benign human papillomavirus-associated lesions and those with penile intraepithelial neoplasia. Data were derived from patient material from a previously published study. Two clinically identical lesions from the same genital site were collected for analysis with routine histopathology and with nested PCR. In total, 292 men were included, of which 47 (16%) had penile intraepithelial neoplasia. Of those with penile intraepithelial neoplasia, 19/47 (40%) reported problems consistent with balanoposthitis, compared with only 15/245 (6%) patients with benign lesions (p < 0.0001). A statistical difference in percentage distribution was also seen regarding morphology (p = 0.001) and location (p = 0.0003) of the lesions among the men having benign lesions with and without balanoposthitis. It is not possible to take biopsies from patients with genital warts, but this study suggests that one probably should be more observant for genital dysplasia among those men with warts with a history of balanoposthitis than those with no such history.

The spectrum of genital human papillomavirus infection among men attending a Swedish sexually-transmitted infections clinic: human papillomavirus typing and clinical presentation of histopathologically benign lesions.

There have been a number of Swedish studies on human papillomavirus (HPV) typing in men, most of which have used less sensitive HPV-typing techniques. The present study included male patients with genital HPV-induced lesions planned for surgery. Samples were prepared for histopathology and PCR. HPV was detected in 233/253 (92%) and HPV 6 or 11 in 89% of the HPV-positive lesions. There were statistically significant differences regarding morphology (p=0.002), location (p=0.000001) and colour (p=0.005) of the lesions for low- vs. mixed or high-risk HPV types. For example, acuminate lesions were mostly found among men with low-risk HPV types, whereas macular lesions were over-represented among them with mixed or high-risk types. The HPV type distribution is similar to that in earlier studies, but we also found correlations with some clinical parameters.

Pre-vaccination incidence of genital warts in 15-23-year-old women and men attending youth clinics in Stockholm, Sweden.

BACKGROUND: Human papillomavirus (HPV) vaccines were introduced to the market in 2006 and 2007. The present pilot study was designed to examine the incidence of genital warts in the population up to 23 y of age in the county of Stockholm before the start of mass HPV vaccination. METHODS: Data from the electronic health records of 9 youth clinics in the county of Stockholm were collected retrospectively for the y 2006-2008. RESULTS: In total, 49,985 patients visited the study youth clinics during 2006-2008. Of these, 1817 were denoted genital warts patients. An extrapolation of the study data was done in an attempt to estimate the annual number of genital warts cases in the full Stockholm County population aged 15-23 y. Results showed that there were approximately 1792 genital warts patients in the age group 15-23 y each year in Stockholm County. Female cases represented approximately 62% of all cases in the age group 15-23 y. The peak incidence was at around 20 y of age for females, while males had a more flattened peak incidence around 19-23 y of age. CONCLUSION: This pilot study demonstrates that, compared to other reported data, genital warts are at least as common in Sweden as in other countries among 15-23 y old females and males.

Occurrence of pharyngeal Chlamydia trachomatis is uncommon in patients with a suspected or confirmed genital infection.

OBJECTIVE: To evaluate how common pharyngeal Chlamydia trachomatis (CT) is among mainly heterosexual women and men with a confirmed or a highly suspicious genital infection having had recent unprotected active oral sex. DESIGN: Prospective observational study. SETTING: Out-patient clinics for sexually transmitted infections in Stockholm. POPULATION: A total of 143 women and 138 men with a confirmed or suspected genital CT infection and a history of active oral sex. METHODS: Pharyngeal samples from men and women in the study population were analyzed for the presence of CT. MAIN OUTCOME MEASURES: Number of positive CT in pharyngeal samples in relation to positive CT in genital samples. RESULTS: Of the women, 9/128 (7.0%) were positive in the pharyngeal samples. None were exclusively positive in the pharynx. Three of 110 men (2.7%) had pharyngeal involvement. One man was positive in the pharynx as well as in the urine sample, and two men were exclusively pharyngeal CT positive. CONCLUSIONS: The finding of CT in the pharynx is not common in spite of the presence of a genital infection and a history of active oral sex.

High occurrence of a new variant of Chlamydia trachomatis escaping diagnostic tests among STI clinic patients in Stockholm, Sweden.

BACKGROUND: In 2006, a genetic variant of Chlamydia trachomatis not detectable with the most commonly used diagnostic tests was identified. Initial reports suggested that as many as 10% to 13% of all chlamydia cases would have remained undiagnosed. The aim of the study was to find the occurrence and clinical findings of this genetic variant among a high-risk population in Stockholm, Sweden. METHODS: Samples were analyzed using the Cobas TaqMan CT test (Roche Diagnostics). To detect the new variant, an additional PCR-analysis, artus C. trachomatis LC MOMP PCR Kit (Qiagen) was performed on all negative samples. Positive results in the artus test were confirmed by a mutant specific PCR. Clinical data were retrospectively collected from medical records. RESULTS: Among 1009 samples analyzed, 115 were positive for C. trachomatis and among those, 27 were found to belong to the genetic altered strain. This variant constituted 23% of all chlamydia cases diagnosed, and 29% were found in the age group 20 to 29 years. Women with the new variant were younger and had more often performed another chlamydia test within the previous 6 months compared with those infected with the wild type. CONCLUSION: These results indicate that a large number of sexually active individuals might be infected despite a negative chlamydia test, thus facilitating a rapid transmission of the new variant. Accordingly, it is of great importance to be aware of limitations of the diagnostic methods used.