Toshiyuki Sasagawa

Etiologic role of human papillomavirus infection in bladder carcinoma

The authors elucidated an etiologic role of human papillomavirus (HPV) infection in carcinoma of the bladder.

Prevalence of human papillomavirus infection in the urinary tract of men with urethritis

Objectives:  To investigate the prevalence of human papillomavirus (HPV) in the genital and urinary tract of men with urethritis.

Etiological role of human papillomavirus infection for inverted papilloma of the bladder

The status of human papillomavirus (HPV) infection in urothelial inverted papilloma was examined in the present study. Formalin‐fixed and paraffin‐embedded tissues from eight cases of inverted papilloma of the bladder were studied. The presence of HPV‐DNA was examined by modified GP5/6+PCR using archival tissue sections by microdissection. HPV genotype was determined with a Hybri‐Max HPV genotyping kit. Immunohistochemical analysis for p16‐INK4a, mcm7, HPV‐E4, and L1, and in situ hybridization for the HPV genome were performed. HPV was detected in seven of eight cases (87.5%) of inverted papilloma. Three cases were diagnosed as inverted papilloma with atypia, while the remaining five were typical cases. HPV‐18 was detected in two cases, including one inverted papilloma with atypia, and HPV‐16 was detected in four cases, including one inverted papilloma with atypia. Multiple HPV type infection was detected in one typical case and one atypical case. High‐risk HPV was present in all HPV‐positive cases. Cellular proteins, p16‐INK4a and mcm7, which are surrogate markers for HPV‐E7 expression, were detected in all HPV‐positive cases, and their levels were higher in inverted papilloma with atypia than in typical cases. In contrast, HPV‐E4 and L1, which are markers for HPV propagation, were observed in some parts of the typical inverted papilloma tissue. High‐risk HPV infection may be one of the causes of urothelial inverted papilloma, and inverted papilloma with atypia may have malignant potential. J. Med. Virol. 83:277–285, 2011.

Intimate Partner Violence and Unintended Pregnancy Among Bangladeshi Women

This study examined the relationship between intimate partner violence (IPV) and unintended pregnancy using data from women reporting IPV in the 2007 Bangladesh Demographic Health Survey. The analysis included 4,695 married women, aged 15 to 40 years, who had at least one birth in the last 5 years. Bivariate and multiple logistic regression analyses were performed to assess the relationship between IPV and pregnancy. About one third (30.4%) of women were abused physically and/or sexually and about one third (30.9%) of their births in the last 5 years were unintended. Compared with women who suffered no IPV, women who were abused sexually had a 1.64-fold increased risk of unintended pregnancy, which is higher than those who suffered physical abuse only (odds ratio: 1.35). The prevalence of unintended pregnancy among those who experienced severe physical violence was 1.60 times higher than those who reported no abuse. The findings indicate a significant relationship between IPV and unintended pregnancy among Bangladeshi women.

Prevalence of genital Mycoplasma, Ureaplasma, Gardnerella, and human papillomavirus in Japanese men with urethritis, and risk factors for detection of urethral human papillomavirus infection

To analyze the risk factors for HPV infection in the urethra, we examined the prevalence of various microorganisms, for example Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum, Gardnerella vaginalis, and human papillomavirus (HPV) in Japanese male patients with urethritis, and investigated their sexual backgrounds. Rubbed samples obtained from the distal urethra and questionnaires regarding sexual activity and demographic information were collected from 176 participants. N. gonorrhoeae, C. trachomatis, M. genitalium, M. hominis, U. urealyticum, U. parvum, G. vaginalis, and HPV were detected in 19, 26, 18, 12, 12, 8.5, 14, and 20%, respectively, of all cases in this study. Multivariate logistic regression analysis indicated that more than 4 sexual partners within the last year and presence of N. gonorrhoeae and/or C. trachomatis and/or M. genitalium infections were independent risk factors for urethral HPV infection, with odds ratios of 3.85 (95% CI 1.49–9.94) and 2.41 (95% CI 1.03–5.61), respectively. It is likely that urethral HPV detection is associated with current sexual activity and the presence of N. gonorrhoeae, C. trachomatis, and/or M. genitalium infections.

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 β-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.

Novel Polymerase Chain Reaction Method for Detecting Cutaneous Human Papillomavirus DNA

There is no simple test to identify the human papillomavirus (HPV) genotypes that cause cutaneous warts. A new polymerase chain reaction (PCR) method, called SK‐PCR, was developed for this purpose. This PCR amplifies 210–238 base pairs of L1 DNA of 17 HPV types (HPV‐1a, ‐2a, ‐3, ‐4, ‐7, ‐10, ‐27, ‐28, ‐29, ‐40, ‐57, ‐60, ‐63, ‐65, ‐77, ‐91, and ‐94), which are thought to cause various cutaneous warts, including common, flat, butchers, punctate, and pigmented warts. The method is novel because the location of these primers is completely different from that of any previous PCR method for HPV. The target sequences are specific to alpha‐, gamma‐, and mu‐papillomaviruses (PVs), but not to beta‐PVs. Furthermore, direct sequencing and restriction fragment length polymorphism (RFLP) were used to determine the HPV genotypes. Fifty of samples of plantar warts were examined, and HPV‐27 was identified in 22 warts, HPV‐57 in 15 warts, and HPV‐2a in 9 warts. These PVs, which are alpha species 4, were the most common. HPV‐4 and ‐65 (gamma‐PVs) and HPV‐1a and ‐63 (mu‐PVs) were detected in one case each. A single HPV type was identified in all of these warts. This method appears to be useful for genotyping the HPVs causing skin warts, and for distinguishing between HPV‐induced warts and warty lesions unrelated to HPV infection. J. Med. Virol. 84:138–144, 2011.

Human papillomavirus infection and pathogenesis in urothelial cells: A mini-review

Several recent studies described that high-risk human papillomavirus (HPV) infection could have a potential role in the development of malignancies other than cervical cancer, such as laryngeal carcinoma, penile carcinoma, and anal carcinoma. However, the etiological role of HPV infection in the pathogenesis of urinary tract has not been clarified. Many epidemiological studies demonstrated that HPV infections frequently occur in the external genitalia through sexual contact; however, it was reported that HPV infection could also occur in the urinary tract, including the urethra and urinary bladder. Some morphological changes of cells associated with HPV infection and mild atypical cells, suspected to be intraneoplasia, were seen in HPV-positive samples obtained from the urinary tract. Some clinical studies and meta-analysis have indicated that HPV infection is likely to have a certain etiological correlation with the development of bladder carcinoma, although its prevalence may vary according to HPV type, study population, region, histological type, detection methods, and other variables. According to the results of previous studies, the prevalence of HPV greatly widely varies in cases of bladder carcinoma. Further research by case-control or large-scales studies is thus required to reach a more definite conclusion.

High prevalence of intermediate‐risk human papillomavirus infection in uterine cervices of kenyan women infected with human immunodeficiency virus

The aim of this study was to investigate an association between certain human papillomavirus (HPV) types and human immunodeficiency virus (HIV) infections. Sexually active females (n = 487; 19–61 years old) were enrolled in the study. Subjects underwent Pap testing and evaluations of HIV and HPV infection status on uterine cervical cell samples. HPV genotyping was performed using a Kurabo GeneSQUARE DNA microarray test. Overall, 23 HPV genotypes were detected, and the most prevalent HPV genotype was HPV‐52, followed by HPV‐39, ‐54, ‐45, ‐56, ‐53, ‐31, ‐42, ‐16, ‐68, and ‐51. HPV‐30, ‐53, ‐54, ‐61, and ‐66, which are associated with abnormal cytology, are categorized as intermediate‐risk in this study. Detection of both high‐ and intermediate‐risk HPV types was significantly associated with cervical abnormality and HIV infection. Multivariate analysis revealed that some high‐risk HPV types (HPV‐31, ‐45, ‐51, ‐56, and ‐59) and most intermediate‐risk HPV types were associated with HIV infection, while the high‐risk types (HPV‐16, ‐18, ‐33, ‐35, ‐39, ‐52, ‐58, and ‐68) were not. The oncogenic effect of the most malignant HPV types (e.g., HPV‐16 and ‐18) appear to be lower, while that of intermediate‐risk types are greater, in areas with a high prevalence of HIV infection. J. Med. Virol. 83:1988–1996, 2011.

Population-based study for human papillomavirus (HPV) infection in young women in Japan: A multicenter study by the Japanese human papillomavirus disease education research survey group (J-HERS)

A multi‐center study was conducted to examine 6,628 eligible Japanese women aged from 16 to 50 years for uterine cervical abnormality and HPV infection with a liquid based‐cytology test and a novel HPV test using the PCR‐SSOP‐Luminex® method identifying 31 HPV genotypes. In 3,047 normal subjects, the overall prevalence across all HPV types was 25%, while that of the common 13 high‐risk (Common‐13HR) types (HPV‐16, 18. 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) was 17%, and that of the definite high‐risk (Definite‐HR) types (HPV‐16, 18. 31, 33, 35, 45, 52, and 58) was 12%. For Definite‐HR, HPV‐52, 16, and 58 were the most common, HPV‐31 was relatively common, and HPV‐18 was less common, while HPV‐33, 35, and 45 were rare. Seven Definite‐HR excluding HPV‐45 and seven Possible‐HR (HPV‐39, 51, 56, 66, 68, 70, and 82) HPV types were identified as a single type infection in patients with high‐grade squamous intraepithelial lesion (HSIL) or worse. The Common‐13HR types were detected in 89% of subjects with HSIL, whereas either Definite‐HR or Possible‐HR types were detected in 95% of HSIL. These 1420 HPV types appear to be involved with HSIL or worse in Japan. The prevalences of multiple‐type HPV infections were identified in roughly half of HPV‐positive subjects, and decreased significantly with age in normal population and abnormal cytology groups, although the prevalences of single‐type infections increased with age in the latter group. Most HPV infections are cleared for some years, while a certain HR‐HPV type persists to induce HSIL. J. Med. Virol. 88:324–335, 2016.