Diversity of Skin Infections

Research output: ThesisDoctoral Thesis (compilation)

Abstract

The identification of infectious agents in cancer has been one of the most rewarding endeavors in cancer research. Currently about 20% of the global cancer burden is linked to an infection. A common characteristic of virus-induced cancer is an increased incidence in immunosuppressed patients, presumably because of impaired host control of virus. Yet non-melanoma skin cancer (NMSC), the cancer that increases most among the immunosuppressed, does not have an established link to infection. NMSC, including squamous cell carcinoma (SCC) and basal cell carcinoma, is the most common cancer among Caucasians. Ultraviolet radiation is an established risk factor.
Human papillomaviruses (HPVs) have been established as the major cause of cervical cancer. Many NMSCs contain one or several cutaneous types of HPV. Exploration of a possible infectious etiology of NMSC requires an unbiased and comprehensive approach for detection of as many infections as possible in the tumor.
We examined NMSCs and other presumably HPV-associated lesions for the presence of unidentified HPV types or other microorganisms, using a combination of multiple displacement amplification (MDA), which amplifies all DNA in a sample without any requirement of prior knowledge of the nucleotide sequence, degenerate “general HPV primers” PCR and high-throughput sequencing. The most common microbial DNA in NMSC was Staphylococcus aureus (S. aureus). We also identified sequences from at least 40 previously not described putative HPV types, of which three novel types (HPV 109, 112 and 114) and an HPV 88 isolate were cloned and completely sequenced. Prevalences and viral loads were investigated in skin and genital samples from different patient groups. S. aureus DNA was more commonly detected in SCC compared to healthy skin (odds ratio, 6.23; 95% confidence interval, 3.10 – 12.53). However, the study design could not determine the causality of the association. HPV 88, 109 and 112 were almost only found in their index patients, whereas HPV114 was found in 1.7% of the female genital samples.
In summary, we find that there is a wide diversity of HPV types in the skin. The association of S. aureus with SCC raises the possibility of general susceptibility to infection in SCC. An association of NMSC with a specific infection remains to be found.

Details

Authors
  • Johanna Ekström
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area

Keywords

  • Human papillomavirus, high-throughput sequencing, Staphylococcus auereus, multiple displacement amplification, non melanoma skin cancer
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
Award date2011 Feb 17
Publisher
  • Avd för medicinsk mikrobiologi
Print ISBNs978-91-86671-62-4
Publication statusPublished - 2011
Publication categoryResearch

Bibliographic note

Defence details Date: 2011-02-17 Time: 09:00 Place: Pathology Lecture Hall, Entrance 78, University Hospital Malmö External reviewer(s) Name: Albert, Jan Title: Professor Affiliation: Department ofMicrobiology, Tumor and Dell Biology, Karolonska Institute, Stockholm, Sweden ---

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