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Diversity of Skin Infections

Ekström, Johanna LU (2011) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2011:13.
Abstract (Swedish)
Popular Abstract in Swedish

Det är väl känt att infektioner kan orsaka eller medverka till utveckling av vissa former av cancer hos människan. Cirka 20% av den globala cancerincidensen orsakas av infektioner. Patienter med nedsatt immunförsvar har en ökad förekomst av ett flertal virus-orsakade cancerformer, t.ex. livmoderhalscancer som orsakas av humant papillomvirus (HPV) och levercancer som orsakas av Hepatit B och C. Upptäckten av dessa samband har möjliggjort att att man numera kan vaccineras mot dessa sjukdomar. Även för icke-melanom hudcancer (NMSC) kan man påvisa en kraftig ökning hos dessa patienter. Hittills har inget samband mellan infektion och NMSC kunnat säkerställas. NMSC, som huvudsakligen består av... (More)
Popular Abstract in Swedish

Det är väl känt att infektioner kan orsaka eller medverka till utveckling av vissa former av cancer hos människan. Cirka 20% av den globala cancerincidensen orsakas av infektioner. Patienter med nedsatt immunförsvar har en ökad förekomst av ett flertal virus-orsakade cancerformer, t.ex. livmoderhalscancer som orsakas av humant papillomvirus (HPV) och levercancer som orsakas av Hepatit B och C. Upptäckten av dessa samband har möjliggjort att att man numera kan vaccineras mot dessa sjukdomar. Även för icke-melanom hudcancer (NMSC) kan man påvisa en kraftig ökning hos dessa patienter. Hittills har inget samband mellan infektion och NMSC kunnat säkerställas. NMSC, som huvudsakligen består av diagnoserna skivepitelcancer och basalcellscancer, är den vanligast förekommande cancern bland vithyade, och ultraviolett ljus är en känd riskfaktor.

HPV orsakar ett flertal sjukdomar; utöver livmoderhalscancer t.ex. även kondylom och cancer i munhålan. I NMSC hittas vanligen flera olika HPV-typer, men de påträffas även i frisk hud. För att kunna undersöka en möjlig association mellan en infektion och NMSC krävs därför en mångsidig objektiv metod som kan upptäcka maximalt antalt patogener i en tumör.

Vi undersökte NMSC och andra möjliga HPV-relaterade lesioner efter förekomst av nya HPV-typer och andra mikroorganismer med en metod som amplifierar allt DNA i ett prov, samt amplifiering med en teknik som kan påvisa många olika HPV-typer följt av sekvensering med en effektiv sekvenseringsteknik. Vi identifierade sekvenser från minst 40 tidigare ej kända HPV typer. Av dessa klonades och helgenomssekvenserades tre typer, HPV 109, 112 och 114, samt den sedan tidigare kända typen HPV 88. HPV 88 och 109 hittades bägge i skivepitelcancer, HPV 112 upptäcktes i ett kondylom och HP114 i en lätt cellförändring i livmoderhalsen. När vi undersökte skivepitelcancer för förekomst av nya HPV-typer och andra mikroorganismer fann vi även flera sekvenser som tillhörde bakterien Staphylococcus aureus (S. aureus).

Vidare undersöktes förekomsten av S. aureus samt HPV 88, 109, 112 och 114 i olika hud- samt genitala prover. Vi fann att DNA från S. aureus var betydligt vanligare i skivepitelcancer än i frisk hud. HPV 88, 109 och 112 är sällsynta virus, medan HPV 114 återfanns i 1.7% av de genitala proven från kvinnor.

Sammanfattninsgvis visar dessa resultat på att mångfalden av HPV i huden är mycket stor. Det faktum att S. aureus var associerat med skivepitelcancer kan visa på en allmän mottaglighet för infektioner av skivepitelcancer och att ett samband mellan skivepitelcancer och en specifik infektion återstår att finna. (Less)
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Albert, Jan, Department ofMicrobiology, Tumor and Dell Biology, Karolonska Institute, Stockholm, Sweden
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Human papillomavirus, high-throughput sequencing, Staphylococcus auereus, multiple displacement amplification, non melanoma skin cancer
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2011:13
pages
104 pages
publisher
Avd för medicinsk mikrobiologi
defense location
Pathology Lecture Hall, Entrance 78, University Hospital Malmö
defense date
2011-02-17 09:00
ISSN
1652-8220
ISBN
978-91-86671-62-4
language
English
LU publication?
yes
id
9f27c0e0-38bb-4db5-af30-99ceb32b7c1b (old id 1769859)
date added to LUP
2011-02-02 09:01:40
date last changed
2016-09-19 08:44:47
@phdthesis{9f27c0e0-38bb-4db5-af30-99ceb32b7c1b,
  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. <br/><br>
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.<br/><br>
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. <br/><br>
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.},
  author       = {Ekström, Johanna},
  isbn         = {978-91-86671-62-4},
  issn         = {1652-8220},
  keyword      = {Human papillomavirus,high-throughput sequencing,Staphylococcus auereus,multiple displacement amplification,non melanoma skin cancer},
  language     = {eng},
  pages        = {104},
  publisher    = {Avd för medicinsk mikrobiologi},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Diversity of Skin Infections},
  volume       = {2011:13},
  year         = {2011},
}