Human papillomavirus type 16 E6 and E7 oncoproteins act synergistically to cause head and neck cancer in mice

Jabbar, Sean F.; Strati, Katerina; Shin, Myeong Kyun; Pitot, Henry C.; Lambert, Paul F.

doi:10.1016/j.virol.2010.08.003

Cited by 63 publications

(69 citation statements)

References 66 publications

(111 reference statements)

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“…Long-term exposure to estrogen is required. These studies have verified the importance of destabilization of pRB, TP53, and PDZ domain proteins in cancer development (Chung et al 2010;Jabbar et al 2010;Maufort et al 2010;Stelzer et al 2010, and references therein).…”

Section: Human Papillomavirus Infectionsmentioning

confidence: 57%

Human Papillomavirus Infections: Warts or Cancer?

Chow

Broker

2013

Cold Spring Harbor Perspectives in Biology

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Human papillomaviruses (HPVs) are prevalent pathogens of mucosal and cutaneous epithe-lia. Productive infections of squamous epithelia lead to benign hyperproliferative warts, condylomata, or papillomas. Persistent infections of the anogenital mucosa by high-risk HPV genotypes 16 and 18 and closely related types can infrequently progress to high-grade intraepithelial neoplasias, carcinomas-in-situ, and invasive cancers in women and men. HPV-16 is also associated with a fraction of head and neck cancers. We discuss the interactions of the mucosotropic HPVs with the host regulatory proteins and pathways that lead to benign coexistence and enable HPV DNA amplification or, alternatively, to cancers that no longer support viral production. H uman papillomaviruses (HPVs) are ubiquitous small DNA viruses that comprise a family of more than 150 genotypes. Closely related types show a predilection for particular epithelial tissues and have similar pathogenic properties (de Villiers et al. 2004; Bravo et al. 2010). The mucosotropic HPVs can be sexually transmitted. Infections are frequently asymp-tomatic and are cleared by the immune systems. Active cases are manifested as hyperproliferative lesions but often regress into subclinical persis-tency within a year. Latent infections can reactivate following immunosuppression or upon undergoing repeated cycles of wounding and healing (Fig. 1). A small fraction of persistent infections by the high-risk (HR) HPV genotypes leads to cancers (reviewed by zur Hausen 2009). Worldwide, each year there are about 500,000 new cases of cervical cancer and 275,000 deaths. More than 99% of cervical cancers are caused by high-risk (HR) HPVs, and types 16 and 18 are responsible for about 70% of the cases (Wal-boomers et al. 1999). The HR HPVs are also responsible for a high percentage of cancers of other anogenital sites in men and women. Moreover, HPV-16 is associated with a fraction of the head and neck neoplasias, in particular tonsillar and oro-pharyngeal cancers (reviewed by Syrjänen 2010). In contrast, infections by the low-risk (LR) types 6 and 11 cause 90% of genital warts and essentially all laryngeal papillomas (recurrent respiratory papillomatosis or RRP) (reviewed by Derkay and Wiatrak 2008) but they rarely result in carcinomas. Juvenile-onset RRP results from transmission in utero or during passage through the birth canal of mothers with active condylomata, yet infections may become symptomatic years later. Recent studies

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Section: Human Papillomavirus Infectionsmentioning

confidence: 57%

Human Papillomavirus Infections: Warts or Cancer?

Chow

Broker

2013

Cold Spring Harbor Perspectives in Biology

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“…The role of high-risk HPV in HNSCC has recently been highlighted in the oropharynx (13), oral cavity (14), larynx (15), hypopharynx (11,12) and in HNSCC metastasis (17). The relevance of the high-risk HPV-E6/E7 protein for the carcinogenesis of multiple head and neck sites was demonstrated in transgenic mice (28)(29)(30). In addition, there is no consensus in the literature to detect HPV infection (20).…”

Section: Discussionmentioning

confidence: 99%

HPV-16/18 detection does not affect the prognosis of head and neck squamous cell carcinoma in younger and older patients

et al. 2012

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Abstract.Recently, high-risk human papillomavirus (HPV) has emerged as a possible agent associated with head and neck squamous cell carcinoma (HNSCC) in younger patients. Therefore, the purpose of the present study was to assess the effect of age on the distribution of HPV-16/18 in HNSCC, together with the impact of the virus on patient prognosis. A longitudinal prospective study was used adjusted for age, gender, TNM staging, smoking status and alcohol consumption. HPV was detected by PCR with consensus primers. Results showed there was no difference in the frequency of HPV-16/18 positivity when younger patients were compared to the older patients. No association was found among highrisk HPV positivity, gender, smoking habit and anatomical site. High-risk HPV was associated with advanced TNM in bivariate analyses; however, it did not impact on survival. Only TNM staging was associated with risk of mortality. Our study supports the theory that age does not affect the presence of HPV-16/18 in HNSCC and has no impact on patient prognosis. The incidence of HNSCC among patients under the age of 45 years is reportedly on the increase worldwide. The factors associated with HNSCC in younger adults are not well established. Findings of this study indicate that HPV-16/18 may not play a role in HNSCC patients under the age of 45 years.

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“…Seven years later, in 1983, we published the first evidence suggesting that a subgroup (some 20 %) of oral cancers is associated with HPV, based on detection of HPV structural proteins in these lesions using an antibody prepared against pooled HPV types [39]. We subsequently identified HPV types 11, 16 and 18 in these samples [40][41][42][43][44][45][46][47][48][49]. This concept has now been well accepted, and a growing body of evidence is supporting that approximately 20 % of oral cancers and 60-80 % of oropharyngeal cancers are caused by HPV [41][42][43][44].…”

Section: Hpv and Head And Neck Cancer (Hnscc)mentioning

confidence: 99%

“…This is supported by a bi-transgenic mouse model of HPV-associated HNSCC, developed by Lambert and coworkers. In this model, K14E6 and K14E7 mice were crossed but E6 and E7 could only induce a suprabasal DNA synthesis in the oral cavity [49,50]. On the contrary, when the mice were treated with the oral carcinogen 4-nitroquinoline-noxide (4-NQO) in their drinking water as a co-carcinogen, the animals were dramatically more susceptible to carcinogenesis and developed tumors almost fully penetrant as compared to the low tumor incidence in the like-treated non-transgenic control group [51].…”

Section: Hpv and Head And Neck Cancer (Hnscc)mentioning

confidence: 99%

“…Subsequently, the same group showed that E7 is the dominant HPV oncoprotein in HNSCC, and they also reported that pRb/p107-deficient mice developed HNSCC as frequently as did HPV-16 E7 transgenic mice. Thus, inactivation of these two pocket proteins by E7 primarily drives E7 oncogenic properties in HPV-positive HNSCC [49]. The HPV copy numbers found in HNSCCs are often lower than detected in cervical cancers.…”

Section: Hpv and Head And Neck Cancer (Hnscc)mentioning

confidence: 99%

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