Oropharyngeal squamous cell carcinoma (OSCC) has shown a gradual increase in male predominance
due to the increasing incidence of human papillomavirus (HPV)-associated OSCC. However, the mode of HPV
transmission to the oral cavity is poorly understood, and little is known about the epidemiology of oral HPV infection in
men. The prevalence rates of HPV, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma spp., and Ureaplasma spp.
were compared in the oropharynx (oral cavity) and urine of male Japanese patients attending a sexually transmitted
disease clinic.
The study population consisted of 213 men aged 16 – 70 years old (mean: 34.4 years old). Oropharyngeal
gargles and urine were collected, and sedimented cells were preserved in liquid-based cytology solution. After DNA
extraction, β-globin and infectious organisms were analyzed by a PCR-based method. The HPV genotype was
determined by HPV GenoArray test.
β-Globin was positive in 100% and 97.7% of oral and urine samples, respectively. HPV detection rates were
18.8% and 22.1% in oral and urine samples, respectively, suggesting that the prevalence of HPV infection in the oral
cavity was similar to that in the urinary tract. N. gonorrhoeae was more prevalent in oral (15.6%) than urine samples
(9.1%), whereas C. trachomatis was detected more frequently in urine (15.9%) than oral samples (4.2%). The detection
rates of M. genitalium, M. hominis, and Ureaplasma spp. were 5.2%, 10.3%, and 16.0% in oral samples, and 7.7%, 6.3%,
and 19.2% in urine, respectively. There were no significant differences in the detection rates of Mycoplasma spp. and
Ureaplasma spp. between anatomical locations. The distribution of HPV types were similar in oral and urine samples,
and HPV16 was the most common type. The majority of men with HPV infection in both the oral cavity and urine had
concordant oral and urinary HPV infection. The presence of urinary HPV infection was an independent risk factor of oral
HPV infection, with an odds ratio of 3.39 (95% CI: 1.49 – 7.71), whereas oral gonococcal infection was inversely
correlated with oral HPV infection (odds ratio: 0.096; 95% CI: 0.01 – 0.77).
In conclusion, oral HPV infection is common in sexually
active men, and its prevalence rate was equivalent to that
in urine samples. In addition, oral HPV infection was significantly
correlated with urinary HPV infection.
1. Zur HH: Papillomavirus infections: a major cause of human cancers.
Biochem Biophys Acta 1996, 1288:F55–78.
2. Miralles-Guri C, Bruni L, Cubilla AL, Castellsagué X, Bosch FX, de Sanjosé S:
Human papillomavirus prevalence and type distribution in penile
carcinoma. J Clin Pathol 2009, 62:870–878.
3. Hoots BE, Palefsky JM, Pimenta JM, Smith JS: Human papillomavirus type
distribution in anal cancer and anal intraepithelial lesions. Int J Cancer
2009, 124:2375–2383.
4. Chaturvedi AK, Engels EA, Anderson WF, Gillison ML: Incidence trends for
human papillomavirus-related and -unrelated oral squamous cell carcinomas
in the United States. J Clin Oncol 2008, 26:612–619.
5. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B,
Goodman MT, Sibug-Saber M, Cozen W, et al: Human papillomavirus and
rising oropharyngeal cancer incidence in the United States. J Clin Oncol
2011, 29:4294–4301.
6. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH,
Chung CH, Jordan RC, Lu C, et al: Human papillomavirus and survival of
patients with oropharyngeal cancer. N Engl J Med 2010, 363:24–35.
7. Tanaka S, Sobue T: Comparison of oral and pharyngeal cancer mortality
in five countries: France, Italy, Japan, UK and USA from the WHO
Mortality Database (1960-2000). Jpn J Clin Oncol 2005, 35:488–491.
8. Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML,
Daniel RW, Viglione M, Symer DE, et al: Evidence for a causal association
between human papillomavirus and a subset of head and neck cancers.
J Natl Cancer Inst 2000, 92:709–720.
9. Smith JS, Melendy A, Melendy A, Rana RK, Pimenta JM: Age-specific
prevalence of infection with human papillomavirus in females: a global
review. J Adolesc Health 2008, 43(Suppl):S5–25.
10. Yamada R, Sasagawa T, Kirumbi LW, Kingoro A, Karanja DK, Kiptoo M,
Nakitare GW, Ichimura H, Inoue M: Human papillomavirus infection and
cervical abnormalities in Nairobi, Kenya, an area with a high prevalence
of human immunodeficiency virus infection. J Med Virol 2008, 80:847–855.
11. Shigehara K, Sasagawa T, Kawaguchi S, Kobori Y, Nakashima T, Shimamura M,
Taya T, Furubayashi K, Namiki M: Prevalence of human papillomavirus
infection in the urinary tract of men with urethritis. Int J Urol 2010,
17:563–568.
12. Grisaru D, Avidor B, Niv J,Marmor S, Almog B, Leibowitz C, Graidy M, GiladiM:
Pilot study of prevalence of high-risk human papillomavirus genotypes in
Israeli Jewish women referred for colposcopic examination. J Clin Microbiol
2008, 46:1602–1605.
13. Chaudhry U, Saluja D: Detection of Neisseria gonorrhoeae by PCR using
orf1 gene as target. Sex Transm Infect 2002, 78:72–78.
14. Mahony JB, Song X, Chong S, Faught M, Salonga T, Kapala J: Evaluation of
the NucliSens Basic Kit for detection of Chlamydia trachomatis and
Neisseria gonorrhoeae in genital tract specimens using nucleic acid
sequence-based amplification of 16S rRNA. J Clin Microbiol 2001,
39:1429–1435.
15. Shigehara K, Kawaguchi S, Sasagawa T, Furubayashi K, Shimamura M, Maeda Y,
Konaka H, Mizokami A, Koh E, Namiki M: Prevalence of genital Mycoplasma,
Ureaplasma, Gardnerella, and human papillomavirus in Japanese men with
urethritis, and risk factors for detection of urethral human papillomavirus
infection. J Infect Chemother 2011, 17:487–492.
16. Stellrecht KA, Woron AM, Mishrik NG, Venezia RA: Comparison of multiplex
PCR assay with culture for detection of genital mycoplasmas. J Clin
Microbiol 2004, 42:1528–1533.
17. D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH,
Gillison ML: Case-control study of human papillomavirus and oropharyngeal
cancer. N Engl JMed 2007, 356:1944–1956.
18. D'Souza G, Agrawal Y, Halpern J, Bodison S, Gillison ML: Oral sexual
behaviors associated with prevalent oral human papillomavirus
infection. J Infect Dis 2009, 199:1263–1269.
19. Kreimer AR, Villa A, Nyitray AG, Abrahamsen M, Papenfuss M, Smith D,
Hildesheim A, Villa LL, Lazcano-Ponce E, Giuliano AR: The epidemiology of
oral HPV infection among a multinational sample of healthy men.
Cancer Epidemiol Biomarkers Prev 2011, 20:172–182.
20. Kreimer AR, Bhatia RK, Messeguer AL, González P, Herrero R, Giuliano AR:
Oral human papillomavirus in healthy individuals: a systematic review of
the literature. Sex Transm Dis 2010, 37:386–391.
21. Marais DJ, Passmore JA, Denny L, Sampson C, Allan BR, Williamson AL:
Cervical and oral human papillomavirus types in HIV-1 positive and
negative women with cervical disease in South Africa. J Med Virol 2008,
80:953–959.
22. Smith EM, Ritchie JM, Yankowitz J, Wang D, Turek LP, Haugen TH: HPV
prevalence and concordance in the cervix and oral cavity of pregnant
women. Infect Dis Obstet Gynecol 2004, 12:45–56.
23. Fakhry C, D’souza G, Sugar E, Weber K, Goshu E, Minkoff H, Wright R,
Seaberg E, Gillison M: Relationship between prevalent oral and cervical
human papillomavirus infections in human immunodeficiency viruspositive
and –negative women. J Clin Microviol 2006, 44:4479–4485.
24. Edelstein ZR, Schwartz SM, Hawes S, Hughes JP, Feng Q, Stern ME, O'Reilly S,
Lee SK, Fu Xi L, Koutsky LA: Rates and determinants of oral human
papillomavirus infection in young men. Sex Transm Dis 2012, 39:860–867.
25. Kawaguchi S, Shigehara K, Sasagawa T, Shimamura M, Nakashima T,
Sugimoto K, Nakashima K, Furubayashi K, Namiki M: Liquid-based urine
cytology as a tool for detection of human papillomavirus, Mycoplasma
spp., and Ureaplasma spp. in men. J Clin Microbiol 2012, 50:401–406.
26. Sasagawa T, Basha W, Yamazaki H, Inoue M: High-risk and multiple human
papillomavirus infections associated with cervical abnormalities in
Japanese women. Cancer Epidemiol Biomarkers Prev 2001, 10:45–52.
27. Takahashi S, Takeyama K, Miyamoto S, Ichihara K, Maeda T, Kunishima Y,
Matsukawa M, Tsukamoto T: Detection of Mycoplasma genitalium,
Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum
DNAs in urine from asymptomatic healthy young Japanese men. J Infect
Chemother 2006, 12:269–271.
28. Sackel SG, Alpert S, Fiumara NJ, Donner A, Laughlin CA, McCormack WM:
Orogenital contact and the isolation of Neisseria gonorrhoeae, Mycoplasma
hominis, and Ureaplasma urealyticum from the pharynx. Sex Transm Dis 1979,
6:64–68.
29. Peters RP, Nijsten N, Mutsaers J, Jansen CL, Morré SA, van Leeuwen AP:
Screening of oropharynx and anorectum increases prevalence of
Chlamydia trachomatis and Neisseria gonorrhoeae infection in female
STD clinic visitors. Sex Transm Dis 2011, 38:783–787.
30. Giuliano AR, Nielson CM, Flores R, Dunne EF, Abrahamsen M, Papenfuss MR,
Markowitz LE, Smith D, Harris RB: The optimal anatomic sites for sampling
heterosexual men for human papillomavirus (HPV) detection: the HPV
detection in men study. J Infect Dis 2007, 196:1146–1152.