Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms.

The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

Head and neck squamous cancers are a heterogeneous group of cancers that arise from the upper aerodigestive tract. Etiologically, these tumors are linked to alcohol/tobacco abuse and infections with high-risk human papillomavirus (HPV). HPV-positive HNSCCs are characterized by a different biology and also demonstrate better therapy response and survival compared to alcohol/tobacco-related HNSCCs. Despite this advantageous therapy response and the clear biological differences, all locally advanced HNSCCs are treated with the same chemo-radiotherapy schedules. Although we have a better understanding of the biology of both groups of HNSCC, the biological factors associated with the increased radiotherapy response are still unclear. Hypoxia, i.e., low oxygen levels because of an imbalance between oxygen demand and supply, is an important biological factor associated with radiotherapy response and has been linked with HPV infections. In this review, we discuss the effects of hypoxia on radiotherapy response, on the tumor biology, and the tumor microenvironment of HPV-positive and HPV-negative HNSCCs by pointing out the differences between these two tumor types. In addition, we provide an overview of the current strategies to detect and target hypoxia.

Hypoxia and Its Influence on Radiotherapy Response of HPV-Positive and HPV-Negative Head and Neck Cancer

Abstract Purpose Human papillomavirus (HPV) infection is the most common sexually transmitted disease, in males and females worldwide. While the role of HPV in female diseases is well known and largely studied, males have negligibly been included in these programs, also because the proportion of women suffering and dying from HPV-related diseases is much larger than men. The aim of this review is to focus on HPV-related diseases in male patients. Methods We performed a literature analysis on the electronic database PubMed. We considered randomized trials, observational and retrospective studies, original articles having as topic the relationship between HPV male infection and the following items: oral, anal penile cancers, warts, condylomas, male infertility, altered sperm parameters, anti-sperm antibodies (ASA). We also included experimental in vitro studies focused on the effects of HPV infection on oocyte fertilization, blastocyst development, and trophoblastic cell invasiveness. In addition, studies describing the adjuvant administration of the HPV vaccination as a possible strategy to promote HPV clearance from semen in infected males were included. Results Regarding head and neck HPV-related diseases, the most important non-neoplastic disease is recurrent respiratory papillomatosis (RRP). Regarding neoplastic diseases, the proportion of head and neck cancers attributable to HPV has increased dramatically worldwide. In addition, nowadays, it is thought that half of head and neck squamous cell carcinomas (HNSCCs) cases in the United States are caused by infection with high-risk HPV. HPV is noteworthy in andrological practice too. It was described as having a high HPV prevalence, ranging between 50 and 70%, in male penile shaft, glans penis/coronal sulcus, semen as well as in scrotal, perianal, and anal regions. Moreover, in male patients, HPV infection has been associated, among other diseases, with penile cancers. HPV semen infection has been reported in about 10% in men from the general population and about 16% in men with unexplained infertility, although these data seem widely underestimated according to clinical experience. In particular, HPV semen infection seems to be most related to asthenozoospermia and to anti-sperm antibodies (ASAs). Conclusions HPV infection represents a health problem with a detrimental social and public impact. Despite this evidence, little has been done to date to widely promote vaccination among young males. 

HPV-related diseases in male patients: an underestimated conundrum.

Ar 2002 drabbades omkring 275 000 individer runt om i varlden av cancer i munhalan. Mer
an halften av dessa kommer att do av sin sjukdom inom 5 ar. Forekomsten av cancer i munhala
och svalg (Oral and Oropharyngeal Squamous Cell Carcinoma, OOSCC) varierar i olika
delar av varlden. Det ar en ovanlig lokalisation av cancer i Sverige, men antalet nya fall okar.
I Sverige svarar sjukdomen for omkring 1 % av all cancer, vilket ar lagt jamfort med forekomsten
i Indien och andra delar av Asien dar den ar en av de vanligaste formerna av cancer.
Studien omfattar 132 konsekutiva patienter i Sodra sjukvardsregionen som under perioden
september 2000 - januari 2004 fatt primardiagnosen OOSCC. De inkluderade patienterna
motsvarar 80 % av samtliga fall. Ur befolkningsregistret identifierades 396 alders-, kons-, och
lansmatchade cancerfria kontrollpersoner av vilka 320 (81 %) samtyckte till att medverka.
Fall och kontroller genomgick en standardiserad intervju, identisk undersokning av munhala
inklusive panoramarontgen samt uppsamling av celler fran munhalan for bestamning av
humant papillomvirus (HPV). En journal speciellt designad for studien anvandes.
Syftet med studien var att utvardera potentiella riskfaktorer for OOSCC - munhygien, tandstatus,
munslemhinneforandringar, alkohol, tobak, virus och vissa livsstilsfaktorer - och att analysera
i vilken grad de var for sig eller tillsammans okar risken for OOSCC. Ett ytterligare
syfte var att bedoma om dessa faktorer paverkar frekvensen av recidiv.
Statistiska analyser visade att medelmattig och dalig munhygien okar risken for OOSCC. Fler
an 20 forlorade tander och/eller daligt fungerande/defekta helproteser utgor ocksa en okad
risk. Regelbundna tandlakarbesok ar daremot forenat med minskad risk for OOSCC.

Risk factors in oral and oropharyngeal squamous cell carcinoma

This year's program committee has put together a program of 7 refereed papers. These papers cover topics on programming language support for building kernels, kernel extensions, embedded systems, parallel data structures, big-data processing systems, and others.

Proceedings of the 8th Workshop on Programming Languages and Operating Systems

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of cancers. Collectively, HNSCC ranks sixth in incidence rate worldwide. Apart from classical risk factors like tobacco and alcohol, infection of human papillomavirus (HPV) is emerging as a discrete risk factor for HNSCC. HPV-positive HNSCC represent a distinct group of diseases that differ in their clinical presentation. These lesions are well-differentiated, occur at an early age, and have better prognosis. Epidemiological studies have demonstrated a specific increase in the proportions of the HPV-positive HNSCC. HPV-positive and HPV-negative HNSCC lesions display different disease progression and clinical response. For tumorigenic-transformation, HPV essentially requires a permissive cellular environment and host cell factors for induction of viral transcription. As the spectrum of host factors is independent of HPV infection at the time of viral entry, presumably entry of HPV only selects host cells that are permissive to establishment of HPV infection. Growing evidence suggest that HPV plays a more active role in a subset of HNSCC, where they are transcriptionally-active. A variety of factors provide a favorable environment for HPV to become transcriptionally-active. The most notable are the set of transcription factors that have direct binding sites on the viral genome. As HPV does not have its own transcription machinery, it is fully dependent on host transcription factors to complete the life cycle. Here, we review and evaluate the current evidence on level of a subset of host transcription factors that influence viral genome, directly or indirectly, in HNSCC. Since many of these transcription factors can independently promote carcinogenesis, the composition of HPV permissive transcription factors in a tumor can serve as a surrogate marker of a separate molecularly-distinct class of HNSCC lesions including those cases, where HPV could not get a chance to infect but may manifest better prognosis.

/pdf/human-papillomavirus-infection-in-head-and-neck-squamous-2v0g833v6y.pdf

Human Papillomavirus Infection in Head and Neck Squamous Cell Carcinomas: Transcriptional Triggers and Changed Disease Patterns.

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Human Papillomavirus Infection in Head and Neck Squamous Cell Carcinomas: Transcriptional Triggers and Changed Disease Patterns.