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Human papillomaviruses of skin and genital lesions

Johansson, Hanna K LU (2014) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2014:93.
Abstract (Swedish)
Popular Abstract in Swedish

Omkring 16% av alla cancerfall i världen beräknas vara orsakade av infektioner och omkring 5% av dessa orsakas av humant papillomvirus (HPV). HPV har etablerats som orsak till livmoderhalscancer och kondylom (könsvårtor). HPV-typer som förekommer på hud har förknippats med icke-melanom hudcancer såsom skivepitelcancer (SCC) men också ofarliga hudhudförändringar som aktinisk keratos (AK). HPV-typer brukar delas upp i sådana som hittas på slemhinnor och sådana som hittas på hud.

Vi har analyserat både hudskador och könsvårtor för förekomst av HPV-DNA, samt uttryck av HPV-mRNA bland celler från livmoderhalsen med lätta cellförändringar.

När vi använde en generell... (More)
Popular Abstract in Swedish

Omkring 16% av alla cancerfall i världen beräknas vara orsakade av infektioner och omkring 5% av dessa orsakas av humant papillomvirus (HPV). HPV har etablerats som orsak till livmoderhalscancer och kondylom (könsvårtor). HPV-typer som förekommer på hud har förknippats med icke-melanom hudcancer såsom skivepitelcancer (SCC) men också ofarliga hudhudförändringar som aktinisk keratos (AK). HPV-typer brukar delas upp i sådana som hittas på slemhinnor och sådana som hittas på hud.

Vi har analyserat både hudskador och könsvårtor för förekomst av HPV-DNA, samt uttryck av HPV-mRNA bland celler från livmoderhalsen med lätta cellförändringar.

När vi använde en generell sekvenseringsteknik för att upptäcka DNA-virus bland hudförändringar (SCC, AK och keratoakantom) fann vi en större mångfald av olika HPV-typer från huden. Totalt identifierade vi DNA-sekvenser från 15 kända HPV-typer, fyra tidigare kända förmodade HPV-typer och två förmodade nya typer. Vi undersökte hur vanliga två av HPV-sekvenserna som hittades var (SE42 och SE46) i olika prover från hud. Det visade sig att dessa var ovanliga (påvisades hos 2% av patienterna) och hittades främst i pinnprover från hudytan. SE42 klonades och är nu erkänd som HPV155.

Vi har identifierat 36 olika slemhinne-HPV-typer i borstprov från ytan av kondylom. Dessa HPV-typer representerar en baslinje av vilka typer som är vanligast före införandet av HPV-vaccinationsprogrammet i Sverige. De tre vanligaste typerna var HPV6 (62%), 16 (13%) och 11 (10%). Efter utökad testning av kondylom som var HPV-negativa (50 st) påvisade vi 21 patienter som var positiva för HPV-typer som normalt hittas på hud, däribland nya HPV153.

Efter generell sekvensering (n = 40) av HPV-negativa kondylom upptäckte vi fyra olika HPV-typer utan också sex kända slemmhinne-typer, men också tre tidigare beskrivna förmodade HPV-typer och 22 nya förmodade hud-typer. Nya HPV175 och HPV180 isolerades.

I mRNA-studien tittade vi på uttrycket av HPV-mRNA i lätta cellförändringar bland celler från livmoderhalsen. mRNA visar på en aktiv infektion. Alla inkluderade kvinnor var HPV-DNA positiva vid starten av studien. Över 90% av proverna var positiva för HPV-mRNA fastän endast ca 30% av kvinnorna utvecklade svårare cellförändringar, förstadier till livmoderhalscancer, under uppföljningsperioden på 4,5 år. Ett HPV-mRNA negativt prov från livmoderhalsen tycks skydda från utveckling av svåra cellförändringar. (Less)
Abstract
Around 5% of all cancer cases worldwide are caused by human papillomavirus (HPV) which has been established as the cause of cervical cancer and genital warts (condylomas). Cutaneous HPV types have been weakly associated with non-melanoma skin lesions such as squamous cell carcinoma (SCC) and actinic keratosis (AK).

We have analyzed skin and genital lesions for presence of HPV-DNA in order to search for unknown and known HPV types. As an attempt to identify women at risk for development of high-grade cervical lesions, HPV E6/E7 mRNA expression was analyzed among women with minor cervical abnormalities.

Metagenomic sequencing identified 15 known HPV types, four previously known HPV types and two novel putative types in... (More)
Around 5% of all cancer cases worldwide are caused by human papillomavirus (HPV) which has been established as the cause of cervical cancer and genital warts (condylomas). Cutaneous HPV types have been weakly associated with non-melanoma skin lesions such as squamous cell carcinoma (SCC) and actinic keratosis (AK).

We have analyzed skin and genital lesions for presence of HPV-DNA in order to search for unknown and known HPV types. As an attempt to identify women at risk for development of high-grade cervical lesions, HPV E6/E7 mRNA expression was analyzed among women with minor cervical abnormalities.

Metagenomic sequencing identified 15 known HPV types, four previously known HPV types and two novel putative types in cutaneous lesions (n=369) and swabs from top of the lesions (n=142) (SCC, AK and keratoacanthoma). The prevalence and viral load of characterized HPV155 and SE46 HPV-isolate was investigated in patients with different cutaneous lesions. HPV155 and SE46 were both found in 2% of patients. HPV178 was characterized from a swab of normal skin next to an actinic keratosis.

A baseline of 36 different HPV types of the alphapapillomavirus genus in 93.9% of condyloma swab samples before HPV vaccination was established. Extended testing among subjects initially negative for HPV (n=50), found 21 patients with cutaneous types of HPV, including novel HPV153. After metagenomic sequencing (n=40) of HPV-negative condylomas, we detected four different HPV types of the alphapapillomavirus genus but also six known HPV types, three previously described putative HPV types and 22 novel putative types of the beta and gammapapillomavirus genera. Novel HPV175 and HPV180 were isolated from the condyloma. HPV153, 175 and 180 are all gamma types.

In the study of high-risk HPV mRNA expression of HPV-DNA positive minor cytological abnormalities (ASCUS; atypical squamous cells of undetermined significance, n=211, and CIN1; cervical intraepithelial neoplasia grade 1, n=131) we observed a high sensitivity (97.2%) but low specificity (10.2%) for detecting future high grade cervical lesions (CIN2+). Presence of HPV E6/E7 mRNA was associated with future development of CIN2+ among high-risk HPV DNA positive women with ASCUS and CIN1. The absence of HPV mRNA demonstrated a tendency for protection against future development of CIN3. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Gyllensten, Ulf, Department of Immunology, Genetics and Pathology, Uppsala University
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Human papillomavirus, condylomas, ASCUS, CIN1, non-melanoma skin cancer, metagenomic sequencing, PCR
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2014:93
pages
71 pages
publisher
Clinical Microbiology, Malmö, Lund University
defense location
Main lecture hall of the department of Pathology, Jan Waldenströms gata 59, Malmö
defense date
2014-09-12 09:00
ISSN
1652-8220
ISBN
978-91-7619-022-7
language
English
LU publication?
yes
id
8b4211d4-bf95-469c-bd18-59cc9c9e4dcd (old id 4589429)
date added to LUP
2014-08-27 12:31:55
date last changed
2016-09-19 08:44:50
@phdthesis{8b4211d4-bf95-469c-bd18-59cc9c9e4dcd,
  abstract     = {Around 5% of all cancer cases worldwide are caused by human papillomavirus (HPV) which has been established as the cause of cervical cancer and genital warts (condylomas). Cutaneous HPV types have been weakly associated with non-melanoma skin lesions such as squamous cell carcinoma (SCC) and actinic keratosis (AK).<br/><br>
We have analyzed skin and genital lesions for presence of HPV-DNA in order to search for unknown and known HPV types. As an attempt to identify women at risk for development of high-grade cervical lesions, HPV E6/E7 mRNA expression was analyzed among women with minor cervical abnormalities.<br/><br>
Metagenomic sequencing identified 15 known HPV types, four previously known HPV types and two novel putative types in cutaneous lesions (n=369) and swabs from top of the lesions (n=142) (SCC, AK and keratoacanthoma). The prevalence and viral load of characterized HPV155 and SE46 HPV-isolate was investigated in patients with different cutaneous lesions. HPV155 and SE46 were both found in 2% of patients. HPV178 was characterized from a swab of normal skin next to an actinic keratosis.<br/><br>
A baseline of 36 different HPV types of the alphapapillomavirus genus in 93.9% of condyloma swab samples before HPV vaccination was established. Extended testing among subjects initially negative for HPV (n=50), found 21 patients with cutaneous types of HPV, including novel HPV153. After metagenomic sequencing (n=40) of HPV-negative condylomas, we detected four different HPV types of the alphapapillomavirus genus but also six known HPV types, three previously described putative HPV types and 22 novel putative types of the beta and gammapapillomavirus genera. Novel HPV175 and HPV180 were isolated from the condyloma. HPV153, 175 and 180 are all gamma types.<br/><br>
In the study of high-risk HPV mRNA expression of HPV-DNA positive minor cytological abnormalities (ASCUS; atypical squamous cells of undetermined significance, n=211, and CIN1; cervical intraepithelial neoplasia grade 1, n=131) we observed a high sensitivity (97.2%) but low specificity (10.2%) for detecting future high grade cervical lesions (CIN2+). Presence of HPV E6/E7 mRNA was associated with future development of CIN2+ among high-risk HPV DNA positive women with ASCUS and CIN1. The absence of HPV mRNA demonstrated a tendency for protection against future development of CIN3.},
  author       = {Johansson, Hanna K},
  isbn         = {978-91-7619-022-7},
  issn         = {1652-8220},
  keyword      = {Human papillomavirus,condylomas,ASCUS,CIN1,non-melanoma skin cancer,metagenomic sequencing,PCR},
  language     = {eng},
  pages        = {71},
  publisher    = {Clinical Microbiology, Malmö, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Human papillomaviruses of skin and genital lesions},
  volume       = {2014:93},
  year         = {2014},
}