The carcinogenicity of HPV infection in the anogenital and oropharyngeal regions is broadly accepted. The aim of the study was to define risk factors for anal and oral HPV infections in high-risk patients with biopsy-proven severe cervical lesions (CIN2+). Altogether immunocompetent 473 females with CIN2+ were categorized into the study group and another 245 women into the control group. The strongest risk factor for anal HPV infection was the presence of cervical HPV infection (p < 0.001). Furthermore, ten or more lifetime sexual partners (p = 0.013), a sexual non-coital contact with the anal area (p < 0.001), and actively practicing anal-penetrative intercourse (p < 0.001) were significantly associated with anal HPV. A history of genital warts in the woman (p = 0.010) and the presence of genital warts in the male partner (p = 0.029) were found statistically significant for the risk of oral HPV infection. Our data suggest that the presence of HPV infection, especially high-risk genotypes, in one anatomical site poses the greatest risk for HPV infection in another anatomical site. The cervix is the main reservoir of infection, but the risk factors for anal and oral HPV infections are dissimilar according to different anatomical distances and more complex routes of transmission.

Department of Gynecology and Obstetrics Bulovka University Hospital 1st Faculty of Medicine Charles University 18081 Prague Czech Republic

Department of Gynecology Obstetrics and Neonatology General University Hospital 1st Faculty of Medicine Charles University 12808 Prague Czech Republic

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Forman D., de Martel C., Lacey C.J., Soerjomataram I., Lortet-Tieulent J., Bruni L., Vignat J., Ferlay J., Bray F., Plummer M., et al. Global burden of human papillomavirus and related diseases. Vaccine. 2012;30((Suppl. S5)):F12–F23. doi: 10.1016/j.vaccine.2012.07.055. PubMed DOI

De Martel C., Georges D., Bray F., Ferlay J., Clifford G.M. Global burden of cancer attributable to infections in 2018: A worldwide incidence analysis. Lancet Glob. Health. 2020;8:e180–e190. doi: 10.1016/S2214-109X(19)30488-7. PubMed DOI

De Martel C., Plummer M., Vignat J., Franceschi S. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int. J. Cancer. 2017;141:664–670. doi: 10.1002/ijc.30716. PubMed DOI PMC

Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. PubMed DOI

Kombe Kombe A.J., Li B., Zahid A., Mengist H.M., Bounda G.A., Zhou Y., Jin T. Epidemiology and Burden of Human Papillomavirus and Related Diseases, Molecular Pathogenesis, and Vaccine Evaluation. Front. Public Health. 2021;8:552028. doi: 10.3389/fpubh.2020.552028. PubMed DOI PMC

Hernandez B.Y., McDuffie K., Zhu X., Wilkens L.R., Killeen J., Kessel B., Wakabayashi M.T., Bertram C.C., Easa D., Ning L., et al. Anal human papillomavirus infection in women and its relationship with cervical infection. Pt 1Cancer Epidemiol. Biomark. Prev. 2005;14:2550–2556. doi: 10.1158/1055-9965.EPI-05-0460. PubMed DOI PMC

Goodman M.T., Shvetsov Y.B., McDuffie K., Wilkens L.R., Zhu X., Ning L., Killeen J., Kamemoto L., Hernandez B.Y. Acquisition of anal human papillomavirus (HPV) infection in women: The Hawaii HPV Cohort study. J. Infect. Dis. 2008;197:957–966. doi: 10.1086/529207. PubMed DOI

Castro F.A., Quint W., Gonzalez P., Katki H.A., Herrero R., van Doorn L.J., Schiffman M., Struijk L., Rodriguez A.C., DelVecchio C., et al. Prevalence of and risk factors for anal human papillomavirus infection among young healthy women in Costa Rica. J. Infect. Dis. 2012;206:1103–1110. doi: 10.1093/infdis/jis458. PubMed DOI PMC

Hernandez B.Y., Ka’opua L.S., Scanlan L., Ching J.A., Kamemoto L.E., Thompson P.J., Zhu X., Shvetsov Y.B., Tofaeono J., Williams V.T. Cervical and anal human papillomavirus infection in adult women in American Samoa. Asia Pac. J. Public Health. 2013;25:19–31. doi: 10.1177/1010539511410867. PubMed DOI PMC

Simonidesová S., Hamšíková E., Klozar J., Tachezy R. The prevalence of oral HPV infection in healthy populations: A systematic review with a focus on European populations. Epidemiol. Mikrobiol. Imunol. 2018;67:175–183. PubMed

Valari O., Koliopoulos G., Karakitsos P., Valasoulis G., Founta C., Godevenos D., Dova L., Paschopoulos M., Loufopoulos A., Paraskevaidis E. Human papillomavirus DNA and mRNA positivity of the anal canal in women with lower genital tract HPV lesions: Predictors and clinical implications. Gynecol. Oncol. 2011;122:505–508. doi: 10.1016/j.ygyno.2011.05.033. PubMed DOI

Marra E., Kroone N., Freriks E., van Dam C.L., Alberts C.J., Hogewoning A.A., Bruisten S., van Dijk A., Kroone M.M., Waterboer T., et al. Vaginal and anal human papillomavirus infection and seropositivity among female sex workers in Amsterdam, the Netherlands: Prevalence, concordance and risk factors. J. Infect. 2018;76:393–405. doi: 10.1016/j.jinf.2017.12.011. PubMed DOI

Morhason-Bello I.O., Baisley K., Pavon M.A., Adewole I.F., Bakare R.A., de Sanjosé S., Francis S.C., Watson-Jones D. Prevalence and genotype distribution of cervical human papillomavirus infection among female sex workers in Asia: A systematic literature review and meta-analysis. PLoS ONE. 2022;17:e0265269. doi: 10.1371/journal.pone.0265269. PubMed DOI PMC

Lin C., Slama J., Gonzalez P., Goodman M.T., Xia N., Kreimer A.R., Wu T., Hessol N.A., Shvetsov Y., Ortiz A.P., et al. Cervical determinants of anal HPV infection and high-grade anal lesions in women: A collaborative pooled analysis. Lancet Infect. Dis. 2019;19:880–891. doi: 10.1016/S1473-3099(19)30164-1. PubMed DOI PMC

Pino M.D., Matas I., Carrillo P., Martí C., Glickman A., Carreras-Dieguez N., Marimon L., Saco A., Rakislova N., Torné A., et al. Natural History of Anal HPV Infection in Women Treated for Cervical Intraepithelial Neoplasia. Cancers. 2023;15:1147. doi: 10.3390/cancers15041147. PubMed DOI PMC

Stier E.A., Sebring M.C., Mendez A.E., Ba F.S., Trimble D.D., Chiao E.Y. Prevalence of anal human papillomavirus infection and anal HPV-related disorders in women: A systematic review. Am. J. Obstet. Gynecol. 2015;213:278–309. doi: 10.1016/j.ajog.2015.03.034. PubMed DOI PMC

Donaire C., Reillo M., Martínez-Escoriza J.C., López-Fernández J.A. Anal study in immunocompetent women with human papillomavirus related lower genital tract pathology. Eur. J. Obstet. Gynecol. Reprod. Biol. 2017;211:15–20. doi: 10.1016/j.ejogrb.2017.01.023. PubMed DOI

Brzeziński M., Stukan M. Anal Cancer and Anal Intraepithelial Neoplasia Risk among Patients Treated for HPV-Related Gynecological Diseases-A Systematic Review. J. Clin. Med. 2023;12:4216. doi: 10.3390/jcm12134216. PubMed DOI PMC

Palefsky J.M., Holly E.A., Ralston M.L., Da Costa M., Greenblatt R.M. Prevalence and risk factors for anal human papillomavirus infection in human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women. J. Infect. Dis. 2001;183:383–391. doi: 10.1086/318071. PubMed DOI

Wei F., Goodman M.T., Xia N., Zhang J., Giuliano A.R., D’Souza G., Hessol N.A., Schim van der Loeff M.F., Dai J., Neukam K., et al. Incidence and Clearance of Anal Human Papillomavirus Infection in 16 164 Individuals, According to Human Immunodeficiency Virus Status, Sex, and Male Sexuality: An International Pooled Analysis of 34 Longitudinal Studies. Clin. Infect. Dis. 2023;76:e692–e701. doi: 10.1093/cid/ciac581. PubMed DOI PMC

Slama J., Sehnal B., Dusek L., Zima T., Cibula D. Impact of risk factors on prevalence of anal HPV infection in women with simultaneous cervical lesion. Neoplasma. 2015;62:308–314. doi: 10.4149/neo_2015_037. PubMed DOI

Steinau M., Hariri S., Gillison M.L., Broutian T.R., Dunne E.F., Tong Z.Y., Markowitz L.E., Unger E.R. Prevalence of cervical and oral human papillomavirus infections among US women. J. Infect. Dis. 2014;209:1739–1743. doi: 10.1093/infdis/jit799. PubMed DOI PMC

Jordan K.H., Beverly Hery C.M., Zhang X., Paskett E.D. Low Rates of Dual-Site and Concordant Oral-Cervical Human Papillomavirus Infections and Cancers: A Systematic Review. Front. Oncol. 2022;12:848628. doi: 10.3389/fonc.2022.848628. PubMed DOI PMC

Nasioutziki M., Chatzistamatiou K., Loufopoulos P.D., Vavoulidis E., Tsampazis N., Pratilas G.C., Liberis A., Karpa V., Parcharidis E., Daniilidis A., et al. Cervical, anal and oral HPV detection and HPV type concordance among women referred for colposcopy. Infect. Agents Cancer. 2020;15:22. doi: 10.1186/s13027-020-00287-7. PubMed DOI PMC

Kedarisetty S., Orosco R.K., Hecht A.S., Chang D.C., Weissbrod P.A., Coffey C.S. Concordant Oral and Vaginal Human Papillomavirus Infection in the United States. JAMA Otolaryngol. Head Neck Surg. 2016;142:457–465. doi: 10.1001/jamaoto.2016.0064. PubMed DOI

Bruno M.T., Boemi S., Caruso G., Sgalambro F., Ferlito S., Cavallaro A., Sudano M.C., Palumbo M. Oral HPV Infection in Women with HPV-Positive Cervix Is Closely Related to Oral Sex. Diagnostics. 2023;13:2096. doi: 10.3390/diagnostics13122096. PubMed DOI PMC

Bajos N., Bozon M., Beltzer N., Laborde C., Andro A., Ferrand M., Goulet V., Laporte A., Le Van C., Leridon H., et al. Changes in sexual behaviours: From secular trends to public health policies. AIDS. 2010;24:1185–1191. doi: 10.1097/QAD.0b013e328336ad52. PubMed DOI

Shigeishi H., Sugiyama M. Risk Factors for Oral Human Papillomavirus Infection in Healthy Individuals: A Systematic Review and Meta-Analysis. J. Clin. Med. Res. 2016;8:721–729. doi: 10.14740/jocmr2545w. PubMed DOI PMC

Smith E.M., Rubenstein L.M., Haugen T.H., Hamsikova E., Turek L.P. Tobacco and alcohol use increases the risk of both HPV-associated and HPV-independent head and neck cancers. Cancer Causes Control. 2010;21:1369–1378. doi: 10.1007/s10552-010-9564-z. PubMed DOI

Gillison M.L., Broutian T., Pickard R.K., Tong Z.Y., Xiao W., Kahle L., Graubard B.I., Chaturvedi A.K. Prevalence of oral HPV infection in the United States, 2009–2010. JAMA. 2012;307:693–703. doi: 10.1001/jama.2012.101. PubMed DOI PMC

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 virus-positive and -negative women. J. Clin. Microbiol. 2006;44:4479–4485. doi: 10.1128/JCM.01321-06. PubMed DOI PMC

Rob F., Tachezy R., Pichlík T., Škapa P., Rob L., Hamšíková E., Šmahelová J., Hercogová J. Concordance of HPV-DNA in cervical dysplasia or genital warts in women and their monogamous long-term male partners. J. Med. Virol. 2017;89:1662–1670. doi: 10.1002/jmv.24824. PubMed DOI