Whole tissue cervical mapping of HPV infection: Molecular evidence for focal latent HPV infection in humans

Hammer, Anne; Koning, Maurits Nc de; Blaakær, Jan; Steiniche, Torben; Doorbar, John; Griffin, Heather; Mejlgaard, Else; Svanholm, Hans; Quint, Wim; Gravitt, Patti E.

doi:10.1016/j.pvr.2019.02.004

Cited by 30 publications

(44 citation statements)

References 33 publications

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“…However, a small number of women have newly detectable infection in middle age and it is not clear whether this is due to a new infection, or reactivation of a latent infection [ 12 ]. Latency has been observed experimentally in rabbit models of papillomavirus infection [ 13 , 14 ], and focal regions of silent infection have been detected in the human cervix [ 15 ]. Therefore, HPV latency could increase the likelihood of persistent infection in the human population.…”

Section: Natural History Of Hpv Infectionmentioning

confidence: 99%

Persistent Human Papillomavirus Infection

Fera

Warburton

Coursey

et al. 2021

Viruses

106

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Persistent infection with oncogenic human papillomavirus (HPV) types is responsible for ~5% of human cancers. The HPV infectious cycle can sustain long-term infection in stratified epithelia because viral DNA is maintained as low copy number extrachromosomal plasmids in the dividing basal cells of a lesion, while progeny viral genomes are amplified to large numbers in differentiated superficial cells. The viral E1 and E2 proteins initiate viral DNA replication and maintain and partition viral genomes, in concert with the cellular replication machinery. Additionally, the E5, E6, and E7 proteins are required to evade host immune responses and to produce a cellular environment that supports viral DNA replication. An unfortunate consequence of the manipulation of cellular proliferation and differentiation is that cells become at high risk for carcinogenesis.

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Section: Natural History Of Hpv Infectionmentioning

confidence: 99%

Persistent Human Papillomavirus Infection

Fera

Warburton

Coursey

et al. 2021

Viruses

106

View full text Add to dashboard Cite

show abstract

“…The lifetime risk of exposure to HPV for women is about 80% and the risk decreases with increasing age (Moscicki et al 2012). Asymptomatic HPV infection of the cervix is also quite frequent (Hammer et al 2019): in the absence of clinical lesions, HPV is detected in the cervix of 11-12% of women. The prevalence of HPV increases with increasing severity of cervical lesions, ranging from 50-70% in low-grade neoplasia to 90-100% in invasive cervical cancer, with HPV16 and 18 detected in the majority of cases alone, combined, or in combination with multiple HPV types (Bruni et al 2010).…”

Section: Cervical Cancermentioning

confidence: 99%

Human papillomavirus-mediated carcinogenesis and tumor progression

Abboodi

Delva

Emmel

et al. 2021

GENOME INSTAB. DIS.

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High-risk human papillomaviruses (HPV) cause 5% of all human cancers and are primary etiologic agents of cervical, anal, and oropharyngeal cancer. HPV infection is necessary, but not sufficient per se to produce cancer: additional changes must occur that transform HPV-infected cells to malignancy. The HPV oncoproteins E6 and E7 immortalize human keratinocytes, cervical cells, and fibroblasts in culture. Each oncoprotein interacts with a variety of cellular binding partners; most important for transformation are E6 and E7's interactions with p53 and RB (respectively) which lead to degradation of p53 and RB through the ubiquitin pathway. Inactivation of p53 and RB leads to inactivation of pivotal cell cycle checkpoints, thereby stimulating cell proliferation and allowing cell division to occur independently of the presence of DNA damage, replicative stress, and other such insults, leading to genome instability. Continuous expression of E6/E7 drives the proliferation and progression of most HPV-mediated cancers of the cervix and a substantial fraction of those of the oropharynx. However, at both cancer sites, "HPV-inactive" tumors that contain HPV DNA, but do not express E6/E7 arise. We propose that these HPV-inactive cancers begin as HPV-driven lesions, but lose E6/E7 expression at some point during progression. We have recently shown that p53 deletion in HPV-immortalized, premalignant cells allows for the emergence of cell populations that no longer express E6/E7. These findings corroborate the notion of a pivotal role of p53 in the context of HPV-mediated transformation, both at the initiation and progression stages of cancer development.

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“…As previously mentioned, it is known that HPV can exist at very low copy numbers, where the virus is present as a non-productive so-called latent infection [ 36 ] which has also been confirmed at multiple sites in individual patients [ 52 ]. Thus, it is possible that superinfection with different HPV types could occur where one of these is present as a low copy number latent infection and it is not clear how such mixed-type HPV infections would contribute to the development of cervical cancer.…”

Section: The Influence Of Hpv Superinfection Superinfection Exclumentioning

confidence: 99%

Potential Effects of Human Papillomavirus Type Substitution, Superinfection Exclusion and Latency on the Efficacy of the Current L1 Prophylactic Vaccines

Hampson

Oliver

Hampson

2020

Viruses

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There are >200 different types of human papilloma virus (HPV) of which >51 infect genital epithelium, with ~14 of these classed as high-risk being more commonly associated with cervical cancer. During development of the disease, high-risk types have an increased tendency to develop a truncated non-replicative life cycle, whereas low-risk, non-cancer-associated HPV types are either asymptomatic or cause benign lesions completing their full replicative life cycle. HPVs can also be present as non-replicative so-called “latent” infections and they can also show superinfection exclusion, where cells with pre-existing infections with one type cannot be infected with a different HPV type. Thus, the HPV repertoire and replication status present in an individual can form a complex dynamic meta-community which changes with respect to both time and exposure to different HPV types. In light of these considerations, it is not clear how current prophylactic HPV vaccines will affect this system and the potential for iatrogenic outcomes is discussed in light of recent outcome data.

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Whole tissue cervical mapping of HPV infection: Molecular evidence for focal latent HPV infection in humans

Cited by 30 publications

References 33 publications

Persistent Human Papillomavirus Infection

Persistent Human Papillomavirus Infection

Human papillomavirus-mediated carcinogenesis and tumor progression

Potential Effects of Human Papillomavirus Type Substitution, Superinfection Exclusion and Latency on the Efficacy of the Current L1 Prophylactic Vaccines

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