Herpes simplex and human papilloma virus coinfections in oral mucosa of men—A 6‐year follow‐up study

Herpes simplex virus (HSV) establishes latency in neurons and recurrent infections in oral mucosa. This prospective study analyzes HSV prevalence in oral mucosal brush samples from men with known human papillomavirus (HPV) status. We hypothesized that HSV‐1‐infection could facilitate HPV persistence as a cofactor. This study was a part of the Finnish Family HPV study accomplished at the University of Turku/Turku University Hospital, Finland. A total of 139 men (mean age 28.6 ± 4.9 years) were enrolled at 36+‐weeks of their partner's pregnancy and thereafter followed‐up for 6 years. Altogether, 722 samples, extracted from oral brush samples collected at the enrollment timepoint (baseline) and at 2‐, 6‐, 12‐, 24‐, 36‐month, and 6 years, were available. HSV DNA was analyzed with quantitative PCR. HSV‐1 results were compared with the known HPV data. The prevalence of oral HSV‐1 shedding varied between 0‐7.2% (mean 2.8%) among the men. Mean copy numbers varied between 4 and 550 genome copies/sample. A total of 18 (12.9%) men were found HSV‐1‐positive at least once, two of them twice. Neither smoking nor oral sex was associated with the oral HSV‐1‐DNA finding. HPV/HSV‐1 co‐infection was found in 6 (4.3%) men, all of them having persistent HPV‐infection. In conclusion, HSV‐1 and its coinfection with HPV in oral mucosa was rare.

[1]  A. Longatto-Filho,et al.  Physical state and copy numbers of HPV16 in oral asymptomatic infections that persisted or cleared during the 6-year follow-up. , 2017, The Journal of general virology.

[2]  M. Lappalainen,et al.  Decrease in seroprevalence for herpesviruses among pregnant women in Finland: cross-sectional study of three time points 1992, 2002 and 2012 , 2016, Infectious diseases.

[3]  S. Grénman,et al.  Carriage of herpes simplex virus and human papillomavirus in oral mucosa is rare in young women: A long-term prospective follow-up. , 2015, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[4]  S. Sanjosé,et al.  HPV DNA, E6/E7 mRNA, and p16INK4a detection in head and neck cancers: a systematic review and meta-analysis. , 2014, The Lancet. Oncology.

[5]  S. Syrjänen,et al.  The combined effects of irradiation and herpes simplex virus type 1 infection on an immortal gingival cell line , 2014, Virology Journal.

[6]  R. Marwaha,et al.  HSV-1 as well as HSV-2 is frequent in oral mucosal lesions of children on chemotherapy , 2014, Supportive Care in Cancer.

[7]  S. Grénman,et al.  Stable marital relationship protects men from oral and genital HPV infections , 2014, European Journal of Clinical Microbiology & Infectious Diseases.

[8]  D. Jamieson,et al.  Pregnancy and Susceptibility to Infectious Diseases , 2013, Infectious diseases in obstetrics and gynecology.

[9]  G. Mcquillan,et al.  Seroprevalence of herpes simplex virus types 1 and 2--United States, 1999-2010. , 2014, The Journal of infectious diseases.

[10]  S. Grénman,et al.  Genotype-Specific Incidence and Clearance of Human Papillomavirus in Oral Mucosa of Women: A Six-Year Follow-Up Study , 2013, PloS one.

[11]  S. Grénman,et al.  Oral mucosa as a reservoir of human papillomavirus: point prevalence, genotype distribution, and incident infections among males in a 7-year prospective study. , 2012, European urology.

[12]  S. Grénman,et al.  Prevalence, Genotype Distribution and Persistence of Human Papillomavirus in Oral Mucosa of Women: A Six-Year Follow-Up Study , 2012, PloS one.

[13]  R. Grenman,et al.  HPV genotypes and their prognostic significance in head and neck squamous cell carcinomas. , 2012, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[14]  M. Röyttä,et al.  Treatment of experimental autoimmune encephalomyelitis in SJL/J mice with a replicative HSV-1 vector expressing interleukin-5 , 2011, Gene Therapy.

[15]  Craig S. Miller,et al.  Human papillomaviruses in oral carcinoma and oral potentially malignant disorders: a systematic review. , 2011, Oral diseases.

[16]  Kari Juhani Syrjänen,et al.  Genotype-specific persistence of genital human papillomavirus (HPV) infections in women followed for 6 years in the Finnish Family HPV Study. , 2010, The Journal of infectious diseases.

[17]  M. Pawlita,et al.  Dynamics of human papillomavirus serology in women followed up for 36 months after pregnancy. , 2009, The Journal of general virology.

[18]  A. Wald,et al.  Rapidly cleared episodes of herpes simplex virus reactivation in immunocompetent adults. , 2008, The Journal of infectious diseases.

[19]  S. Porter,et al.  Herpes Simplex Virus Type 1 infection: overview on relevant clinico-pathological features. , 2007, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[20]  A. Wald,et al.  Effect of maternal herpes simplex virus (HSV) serostatus and HSV type on risk of neonatal herpes , 2007, Acta obstetricia et gynecologica Scandinavica.

[21]  N. Park,et al.  Bmi-1 cooperates with human papillomavirus type 16 E6 to immortalize normal human oral keratinocytes. , 2007, Experimental cell research.

[22]  S. Grénman,et al.  Transmission of High-Risk Human Papillomavirus (HPV) between Parents and Infant: a Prospective Study of HPV in Families in Finland , 2005, Journal of Clinical Microbiology.

[23]  A. Wald,et al.  Oral shedding of herpes simplex virus type 2 , 2004, Sexually Transmitted Infections.

[24]  H. D. de Melker,et al.  The seroepidemiology of herpes simplex virus type 1 and 2 in Europe , 2004, Sexually Transmitted Infections.

[25]  J. Ilonen,et al.  Development of Antibodies Against Cytomegalovirus, Varicella-zoster Virus and Herpes Simplex Virus in Finland During the First Eight Years Of Life: A Prospective Study , 2003, Scandinavian journal of infectious diseases.

[26]  G. Löwhagen,et al.  Prevalence of Herpes Simplex Virus Antibodies in Childhood and Adolescence: A Cross-sectional Study , 2003, Scandinavian journal of infectious diseases.

[27]  V. Hukkanen,et al.  Time-Resolved Fluorometry PCR Assay for Rapid Detection of Herpes Simplex Virus in Cerebrospinal Fluid , 2000, Journal of Clinical Microbiology.

[28]  W. Leong,et al.  A prospective study of new infections with herpes simplex virus type 1 and type 2. Chiron HSV Vaccine Study Group. , 1999, The New England journal of medicine.

[29]  L. Harel,et al.  Treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study , 1997, BMJ.

[30]  Y. Toh,et al.  Detection of herpes simplex virus (HSV) in the saliva from 1,000 oral surgery outpatients by the polymerase chain reaction (PCR) and virus isolation. , 1994, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[31]  H. Fox,et al.  Detection and typing of human papillomavirus in archival cervical cancer specimens by DNA amplification with consensus primers. , 1990, Journal of the National Cancer Institute.

[32]  W. Quint,et al.  Use of anticontamination primers in the polymerase chain reaction for the detection of human papilloma virus genotypes in cervical scrapes and biopsies , 1989, Journal of medical virology.

[33]  S. Yamamoto,et al.  Shedding of herpes simplex virus type 1 into saliva. , 1988, Journal of oral pathology.

[34]  Shirley A. Miller,et al.  A simple salting out procedure for extracting DNA from human nucleated cells. , 1988, Nucleic acids research.

[35]  L. Corey,et al.  Recurrences after oral and genital herpes simplex virus infection. Influence of site of infection and viral type. , 1987, The New England journal of medicine.

[36]  R. Reichman Herpes simplex virus infections , 1984, European Journal of Clinical Microbiology.

[37]  S. Spruance Pathogenesis of herpes simplex labialis: excretion of virus in the oral cavity , 1984, Journal of clinical microbiology.

[38]  G. Krueger,et al.  The natural history of recurrent herpes simplex labialis: implications for antiviral therapy. , 1977, The New England journal of medicine.

[39]  J. Baringer,et al.  Recovery of herpes-simplex virus from human trigeminal ganglions. , 1973, The New England journal of medicine.

[40]  S. Grénman,et al.  Smoking increases oral HPV persistence among men: 7-year follow-up study , 2013, European Journal of Clinical Microbiology & Infectious Diseases.

[41]  Craig S. Miller,et al.  Asymptomatic shedding of herpes simplex virus (HSV) in the oral cavity. , 2008, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[42]  P. Moore,et al.  Persistence in the population: epidemiology and transmisson -- Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis , 2007 .

[43]  A. Wald,et al.  Persistence in the population: epidemiology, transmission , 2007 .

[44]  J. Benichou [Herpetic stomatitis]. , 1987, Soins. Gynecologie, obstetrique, puericulture, pediatrie.

[45]  E. Petersen,et al.  Herpes simplex viruses. , 2009 .