Liquid-Based Urine Cytology as a Tool for Detection of Human Papillomavirus, Mycoplasma spp., and Ureaplasma spp. in Men

Abstract

Liquid-based urine cytology (LB-URC) was evaluated for cytological diagnosis and detection of human papillomavirus (HPV), Mycoplasma, and Ureaplasma. Midstream urine samples were collected from 141 male patients with urethritis and 154 controls without urethritis, and sediment cells were preserved in liquid-based cytology solution. Urethral swabs from urethritis patients were tested for the presence of Neisseria gonorrhoeae and Chlamydia trachomatis. Papanicolaou tests were performed for cytological evaluation. HPV, Mycoplasma, and Ureaplasma genomes were determined by PCR-based methods, and localization of HPV DNA in urothelial cells was examined by in situ hybridization (ISH). The ␤-globin gene was positive in 97.9% of LB-URC samples from urethritis patients and in 97.4% of control samples, suggesting that high-quality cellular DNA was obtained from the LB-URC samples. HPV DNA was detected in 29 (21.0%) urethritis cases and in five (3.3%) controls (P < 0.05). HPV type 16 (HPV 16) was most commonly found in urethritis patients. Cytological evaluations could be performed for 92.1% of urethritis patients and 64.3% of controls. Morphological changes suggestive of HPV infection were seen in 20.7% of the HPV-positive samples, and ISH demonstrated the presence of HPV DNA in both squamous and urothelial cells in HPV-positive samples. Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum were detected in 14.5%, 10.9%, 6.5%, and 12.3% of urethritis patients, respectively. The prevalence rates of these microorganisms (except Ureaplasma parvum) were significantly higher in urethritis cases than controls (P < 0.05). LB-URC is applicable for detection of HPV, Mycoplasma, and Ureaplasma. HPV infection occurs in urothelial cells, especially in gonococcal urethritis. Human papillomavirus (HPV) infection is known to cause uterine cervical cancer and precancerous lesions in women (14,29). HPV infection usually occurs through sexual intercourse, and it has been reported that the prevalence of HPV infection in sexually active healthy young women ranges from 20% to 60% (12,19,26). Thus, cervical HPV infection is thought to be one of the most common sexually transmitted infections (STIs) in women.Prophylactic HPV vaccine has become available worldwide to prevent cervical cancer, and the prevalence and sites of HPV infection in the male genital tract have been studied. Some studies indicated that the external male genitalia, including the penile shaft, glans, coronal sulcus, and prepuce, are the most common sites of HPV infection and that the prevalence of HPV among healthy young men is as high as that among healthy young women (9, 10). However, a systematic review indicated that the HPV detection rate in urine was less than 7% and that urine is unsuitable for HPV detection in epidemiological studies (9). Indeed, Giuliano et al examined the presence of HPV DNA in multiple genital sites of 186 healthy men and reported that HPV was detected most commonly on the penile shaft (49.9%), followed by the gl...

Human papillomavirus prevalence in the anus and urine among HIV-infected Japanese men who have sex with men

“…A previous Japanese study showed that HPV-DNA was detected in 21.0% of urine samples of 141 MSW with urethritis and in 3.3% of urine samples in 154 healthy men [16]. Nakashima et al reported an HPV prevalence of 22.1% based on urine samples of 213 Japanese MSW attending a STIs clinic [18].…”

“…This kit can determine 37 HPV genotypes, consisting of 15 high-risk HPV types (16,18,31,33,35,39,45, 51, 52, 56, 58, 59, 68, 73, 82), 10 low-risk HPV types (6,11,42,43,44,54,61,70,72,81), and 12 unknown-risk types (26,34,40,53,55,57,66,67,69,71,83,84), by flow-through hybridization and gene-chip methods using HPV-DNA amplified by PCR [17,19].…”

“…In addition, some recent studies have suggested that the urinary tract can also be alternative site for HPV infection among men in addition to external genitalia and anus, and urine samples are used as a convenient tool for testing HPV infections in the urinary tract [15,16]. A broad range of HPV prevalence rate has been reported in urine samples of healthy men and urethritis men [16e18].…”

Editorial Comment to Human papillomavirus‐related basaloid squamous cell carcinoma of the bladder associated with genital tract human papillomavirus infection

“…1 In addition, in a recent study, HPV-positive samples obtained from the urinary tract showed some morphological changes observed in cells associated with HPV infection as well as some mild atypical cells, suspected to be neoplastic. 2 In fact, a recent meta-analysis with 19 case-control studies reported a HPV prevalence of 16.88% (95% confidence interval 15.53-18.31%) among bladder carcinoma cases, most of which were high-risk HPV types. These findings suggest that infection with high-risk HPV types, especially HPV type 16, could play a role in bladder carcinogenesis, although its prevalence can vary according to HPV type, study population, region, histological type, detection methods and other variables.…”

“…Recent studies showed that HPV infection could also occur in the urinary tract, including the urethra and urinary bladder . In addition, in a recent study, HPV‐positive samples obtained from the urinary tract showed some morphological changes observed in cells associated with HPV infection as well as some mild atypical cells, suspected to be neoplastic . In fact, a recent meta‐analysis with 19 case–control studies reported a HPV prevalence of 16.88% (95% confidence interval 15.53–18.31%) among bladder carcinoma cases, most of which were high‐risk HPV types.…”