Human papillomaviruses of skin and genital lesions

Hanna K Johansson

Human papillomaviruses of skin and genital lesions

Hanna K Johansson

Klinisk mikrobiologi, Malmö

Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)

550 Nedladdningar (Pure)

Sammanfattning

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.

Originalspråk	engelska
Kvalifikation	Doktor
Tilldelande institution	Klinisk mikrobiologi, Malmö
Handledare	Forslund, Ola, handledare Dillner, Joakim, handledare
Tilldelningsdatum	2014 sep. 12
Förlag	Clinical Microbiology, Malmö, Lund University
ISBN (tryckt)	978-91-7619-022-7
Status	Published - 2014

Bibliografisk information

Defence details

Date: 2014-09-12
Time: 09:00
Place: Main lecture hall of the department of Pathology, Jan Waldenströms gata 59, Malmö

External reviewer(s)

Name: Gyllensten, Ulf
Title: [unknown]
Affiliation: Department of Immunology, Genetics and Pathology, Uppsala University

---

Ämnesklassifikation (UKÄ)

Mikrobiologi inom det medicinska området

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4 Artikel i vetenskaplig tidskrift

Complete genome sequences of three novel human papillomavirus types, 175, 178, and 180.
Johansson, H. K. & Forslund, O., 2014, I: Genome Announcements. 2, 3
Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Fil
218 Nedladdningar (Pure)
Human papillomavirus typing in reporting of condyloma.
Sturegård, E., Johansson, H. K., Ekström, J., Hansson, B-G., Johnsson, A., Gustafsson, E., Dillner, J. & Forslund, O., 2013, I: Sexually Transmitted Diseases. 40, 2, s. 123-129
Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review
Metagenomic sequencing of "HPV-negative" condylomas detects novel putative HPV types.
Johansson, H. K., Bzhalava, D., Ekström, J., Hultin, E., Dillner, J. & Forslund, O., 2013, I: Virology. 440, 1, s. 1-7
Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

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@phdthesis{8b4211d4bf95469cbd1859cc9c9e4dcd,

title = "Human papillomaviruses of skin and genital lesions",

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 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.",

keywords = "Human papillomavirus, condylomas, ASCUS, CIN1, non-melanoma skin cancer, metagenomic sequencing, PCR",

author = "Johansson, {Hanna K}",

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language = "English",

isbn = "978-91-7619-022-7",

series = "Lund University Faculty of Medicine Doctoral Dissertation Series ",

publisher = "Clinical Microbiology, Malm{\"o}, Lund University",

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N1 - Defence details Date: 2014-09-12 Time: 09:00 Place: Main lecture hall of the department of Pathology, Jan Waldenströms gata 59, Malmö External reviewer(s) Name: Gyllensten, Ulf Title: [unknown] Affiliation: Department of Immunology, Genetics and Pathology, Uppsala University ---

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Human papillomavirus

KW - condylomas

KW - ASCUS

KW - CIN1

KW - non-melanoma skin cancer

KW - metagenomic sequencing

KW - PCR

M3 - Doctoral Thesis (compilation)

SN - 978-91-7619-022-7

T3 - Lund University Faculty of Medicine Doctoral Dissertation Series

PB - Clinical Microbiology, Malmö, Lund University

ER -

Human papillomaviruses of skin and genital lesions

Sammanfattning

Bibliografisk information

Ämnesklassifikation (UKÄ)

FN:s Globala mål

Tillgång till dokument

Fingeravtryck

Forskningsoutput

Complete genome sequences of three novel human papillomavirus types, 175, 178, and 180.

Human papillomavirus typing in reporting of condyloma.

Metagenomic sequencing of "HPV-negative" condylomas detects novel putative HPV types.

Citera det här