Genital Human Papillomavirus (HPV) Concordance in Heterosexual Couples

Nyitray, Alan G.; Menezes, Lynette; Lu, Binfeng; Lin, Hui‐Yi; Smith, Danélle; Abrahamsen, Martha; Papenfuss, Mary; Gage, Christine; Giuliano, Anna R.

doi:10.1093/infdis/jis327

Cited by 37 publications

(24 citation statements)

References 25 publications

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“…Current studies have shown that the overall prevalence of HPV among sexually active men and women is ϳ50% (61,62). However, only a small subset of these infections result in persistent infections, and even a smaller percentage of persistently infected individuals develop cancer.…”

Section: Discussionmentioning

confidence: 99%

APOBEC3A Functions as a Restriction Factor of Human Papillomavirus

Warren

Guo

et al. 2015

J Virol

174

203

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Human papillomaviruses (HPVs) are small DNA viruses causally associated with benign warts and multiple cancers, including cervical and head-and-neck cancers. While the vast majority of people are exposed to HPV, most instances of infection are cleared naturally. However, the intrinsic host defense mechanisms that block the early establishment of HPV infections remain mysterious. Several antiviral cytidine deaminases of the human APOBEC3 (hA3) family have been identified as potent viral DNA mutators. While editing of HPV genomes in benign and premalignant cervical lesions has been demonstrated, it remains unclear whether hA3 proteins can directly inhibit HPV infection. Interestingly, recent studies revealed that HPV-positive cervical and head-and-neck cancers exhibited higher rates of hA3 mutation signatures than most HPV-negative cancers. Here, we report that hA3A and hA3B expression levels are highly upregulated in HPV-positive keratinocytes and cervical tissues in early stages of cancer progression, potentially through a mechanism involving the HPV E7 oncoprotein. HPV16 virions assembled in the presence of hA3A, but not in the presence of hA3B or hA3C, have significantly decreased infectivity compared to HPV virions assembled without hA3A or with a catalytically inactive mutant, hA3A/E72Q. Importantly, hA3A knockdown in human keratinocytes results in a significant increase in HPV infectivity. Collectively, our findings suggest that hA3A acts as a restriction factor against HPV infection, but the induction of this restriction mechanism by HPV may come at a cost to the host by promoting cancer mutagenesis. IMPORTANCEHuman papillomaviruses (HPVs) are highly prevalent and potent human pathogens that cause >5% of all human cancers, including cervical and head-and-neck cancers. While the majority of people become infected with HPV, only 10 to 20% of infections are established as persistent infections. This suggests the existence of intrinsic host defense mechanisms that inhibit viral persistence. Using a robust method to produce infectious HPV virions, we demonstrate that hA3A, but not hA3B or hA3C, can significantly inhibit HPV infectivity. Moreover, hA3A and hA3B were coordinately induced in HPV-positive clinical specimens during cancer progression, likely through an HPV E7 oncoprotein-dependent mechanism. Interestingly, HPV-positive cervical and head-and-neck cancer specimens were recently shown to harbor significant amounts of hA3 mutation signatures. Our findings raise the intriguing possibility that the induction of this host restriction mechanism by HPV may also trigger hA3A-and hA3B-induced cancer mutagenesis. Human papillomaviruses (HPVs) are small, nonenveloped DNA viruses known as one of the most prevalent sexually transmitted pathogens. Among almost 200 different genotypes, ϳ24 high-risk HPV genotypes are causally associated with multiple human cancers, including nearly all cervical cancers and a portion of head-and-neck squamous cell carcinomas (1). From 1988 to 2004, the incidence of HPV-associ...

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Section: Discussionmentioning

confidence: 99%

APOBEC3A Functions as a Restriction Factor of Human Papillomavirus

Warren

Guo

et al. 2015

J Virol

174

203

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“…In addition to actual transmission studies, cervical HPV infection in a man’s female sexual partner has been found to be a risk for the man’s genital HPV infection [24]. Other risk factors for type-specific concordance were (1) an increasing number of younger couples, (2) persistent HPV infection, (3) higher frequency of sexual intercourse, (4) rising number of spouse’s lifetime sexual partners, as well as (5) sexual relations with prostitutes [9, 14, 19, 25]. A recent systematic review evaluated the risk of cancer among spouses of patients with HPV-related cancer [25].…”

Section: Risk Factors For Hpv Concordance In Heterosexual Couplesmentioning

confidence: 99%

HPV Infections in Heterosexual Couples: Mechanisms and Covariates of Virus Transmission

Kero

Rautava

2019

Acta Cytologica

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Sexual intercourse is regarded as the primary route of human papillomavirus (HPV) transmission. Reported rates of the genotype-specific genital concordance of HPV infection among heterosexual partners vary. Most studies have evaluated only male/female genital transmission, but lately, the oral region has gained interest because of a rising trend of HPV-associated oropharyngeal cancer. Risk factors for type-specific concordance have been reported as an increasing number of younger couples, persistent HPV infection, higher frequency of sexual intercourse, rising number of spouse’s lifetime sexual partners, and sexual relations with prostitutes. However, the concordance of the same genital HPV genotype does not absolutely mean that it has been transmitted by the current partner. There are also other possible non-sexual transmission routes. The detected HPV infection may also be a reactivation of a previous infection. The high complexity of HPV transmission dynamics within an individual him-/herself as well as within sexual couples is discussed in this article.

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“…Heterosexual HIV-negative adult men have also been shown to have an overall HPV prevalence of approximately 50% [14]. Concordance of HPV infection between sexual partners is variable and ranges from 40% to 60%, which may be affected by length of sexual relationship, frequency of intercourse, condom use and number of lifetime sexual partners [15, 16]. The overall transmission rate from one heterosexual partner to the other over a 6-month period is estimated to be 3.7 cases per 100 person-months [17].…”

Section: Role Of Hpv Infectionmentioning

confidence: 99%

Human Immunodeficiency Virus/AIDS, Human Papillomavirus, and Anal Cancer

Wang

Sparano

Palefsky

2017

Surgical Oncology Clinics of North America

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SYNOPSIS Anal cancer is an increasingly common non-AIDS-defining cancer among HIV-infected individuals. It is associated with human papillomavirus (HPV), the most common sexually transmitted infectious agent. The 14 oncogenic types of HPV are causally associated with 5–10% of all cancers, notably anogenital cancers. HPV16 is the most common genotype detected in about 70% of anal cancers. The HPV types detected in anal cancer are included in the 9-valent vaccine. HPV vaccines have demonstrated efficacy in reducing anal precancerous lesions in HIV-infected individuals. The standard treatment for anal cancer has been fluorouracil (5-FU) and mitomycin (or cisplatin) as chemotherapy agents plus radiation, which can also be effectively used for the HIV-infected patients. Continued studies will be needed to test new treatment strategies in HIV-infected patients with anal cancer to determine which treatment protocols provide the best therapeutic index.

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Genital Human Papillomavirus (HPV) Concordance in Heterosexual Couples

Abstract: Genital HPV concordance was common. Viral infectiousness and number of sex partners may help explain concordance among heterosexual partners.

Cited by 37 publications

References 25 publications

APOBEC3A Functions as a Restriction Factor of Human Papillomavirus

APOBEC3A Functions as a Restriction Factor of Human Papillomavirus

HPV Infections in Heterosexual Couples: Mechanisms and Covariates of Virus Transmission

Human Immunodeficiency Virus/AIDS, Human Papillomavirus, and Anal Cancer

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