Human Papillomavirus-DNA Loads in Actinic Keratoses Exceed those in Non-Melanoma Skin Cancers

Abstract

Recent studies suggest a role of cutaneous human papillomaviruses (HPV) in non-melanoma skin cancer (NMSC) development. In this study viral DNA loads of six frequent HPV types were determined by quantitative, type-specific real-time-PCR (Q-PCR) in actinic keratoses (AK, n=26), NMSC (n=31), perilesional tissue (n=22), and metastases of squamous cell carcinomas (SCC) (n=8) which were previously shown to be positive for HPV5, 8, 15, 20, 24, or 36. HPV-DNA loads in AK, (partially microdissected) NMSC, and perilesional skin ranged between one HPV-DNA copy per 0.02 and 14,200 cell equivalents (median: 1 HPV-DNA copy per 344 cell equivalents; n=48). In 32 of the 79 HPV-positive skin biopsies and in seven of the eight metastases viral loads were even below the detection limit of Q-PCR. Low viral loads in NMSC were confirmed by in situ-hybridization showing only a few HPV-DNA-positive nuclei per section. Viral loads in SCC, basal cell carcinomas, and perilesional tissue were similar. But, viral loads found in AK were significantly higher than in SCC (p=0.035). Our data suggest that persistence of HPV is not necessary for the maintenance of the malignant phenotype of individual NMSC cells. Although a passenger state cannot be excluded, the data are compatible with a carcinogenic role of HPV in early steps of tumor development.

Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients

“…To date, the evidence suggesting a causal role of b-HPV in skin cancer has been tainted by: the finding that viral DNA is also found in normal skin, that discovery of the viral genome copy number is usually much less than one viral genome per tumor cell and the fact that viral transcripts have not been identified by high-throughput mRNA sequencing. 19,[54][55][56][57] Alongside the fact that ubiquitous b-HPV DNA carriage does not necessarily indicate active infection, these issues have created and so far maintained a state of uncertainty about the causative role of b-HPVs in non-epidermodysplasia verruciformis skin cancer. Although the present study does not directly demonstrate a causal role of these viruses, the detection of E4 and L1 positivity in (i) actinic keratosis, which are widely regarded to be squamous cell carcinoma precursors or in situ carcinoma, and (ii) the adjacent pathological epithelium of one squamous cell carcinoma and one basal cell carcinoma, clearly shows that b-HPV are actively replicating in the lesional skin of organ transplant recipients and can therefore cooperate with other carcinogenic agents, such as UVB, favoring skin cancer promotion and progression.…”

A case‐control study of cutaneous squamous cell carcinoma among Caucasian organ transplant recipients: The role of antibodies against human papillomavirus and other risk factors

“…38 The prevalence of antibodies against different HPV-L1 antigens varies from study to study and any association might be a consequence of increased viral replication after cell proliferation in patients with cutaneous SCC (this may also explain associations identified for other proliferative skin lesions, such as psoriasis or burns). 13 Low HPV-DNA copy numbers in tumour cells 39 and the lack of HPV integration to the host-DNA 40 would also support this theory. It is possible that the increased risk of SCC observed in OTR is simply a result of immunosuppression impairing the normal capacity to repair UV-damaged DNA.…”

Prevalência e diversidade de beta-papilomavírus em amostras anogenitais e orais de homens do estudo HIM

“…Além disso, estudos apontam para o possível papel desses vírus em estágios precoces da carcinogênese cutânea em indivíduos imunocompetentes e imunossuprimidos Rollison et al, 2008;Weissenborn et al, 2005).…”

“…Foi observado que em lesões de pele em uma população saudável, o número de cópias de HPV cutâneos é maior que o registrado em lesões pré-câncer advindas destes, assim como em lesão NMSC posteriormente desenvolvidas. Visando compreender melhor este achado, ensaios de hibridização in situ das lesões pré-câncer confirmaram que poucos núcleos eram positivos para DNA de HPV (Weissenborn et al, 2005). Além disso, análises de transcritos virais de alguns tipos de β-HPV tem sugerido que estes vírus não apresentam atividade 27 transcricional em indivíduos com SCC não portadores de EV .…”

“…Com o advento da metagenômica e sequenciamento de nova geração, tem se tornado possível registrar uma larga diversidade de tipos cutâneos nunca observada, com mais de 50 tipos virais já descritos para cada um destes gêneros cutâneos, sendo prevista a caracterização de mais centenas de novos isolados num futuro próximo revisado por de Villiers, 2013; Chahoud et al, 2015;Reuschenbach et al, 2011;Rollison et al, 2008;. Ulrich et al, 2008;Weissenborn et al, 2005).…”