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Human papillomavirus testing and its application in cervical cancer prevention

Söderlund Strand, Anna LU (2008) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2008:116.
Abstract
SUMMARY

Because of the strong causal relationship between persistent infections of human

papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN) and cancer, HPVtesting

has been proposed for improvement of cervical screening programs, including

triaging and follow-up after treatment for CIN. We developed two new methods for

HPV-testing with genotyping: A high-throughput HPV genotyping method that uses

mass spectrometry for detection of the products of type-specific mass extend

reactions, and a method with particularly sensitive detection of a broad spectrum of

HPV-types, also in the case of multiple infections, that uses type-specific probes

coupled... (More)
SUMMARY

Because of the strong causal relationship between persistent infections of human

papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN) and cancer, HPVtesting

has been proposed for improvement of cervical screening programs, including

triaging and follow-up after treatment for CIN. We developed two new methods for

HPV-testing with genotyping: A high-throughput HPV genotyping method that uses

mass spectrometry for detection of the products of type-specific mass extend

reactions, and a method with particularly sensitive detection of a broad spectrum of

HPV-types, also in the case of multiple infections, that uses type-specific probes

coupled to fluorescent beads for detection on the Luminex platform.

The utility of HPV-testing was evaluated in 3 different studies:

A general primer PCR-based genotyping method and the commercial Hybrid Capture

(HCII) assay were compared for sensitivity and specificity for detection of CIN in

secondary screening and in follow-up after treatment for cervical dysplasia. The

sensitivities were high for both methods, although somewhat higher for the PCR

method, but the concordance between the methods was substantial.

The performance of HPV-genotyping for prediction of recurrence after treatment for

CIN was compared to that of cytology. Only HPV-genotyping could predict all cases

of CIN grade II or worse in histopathology, and all cases of CIN I or worse in

cytology during follow-up had persistence of HPV.

The applicability of HPV-genotyping was also evaluated in a secondary screening

setting. Different high-risk HPV types had substantial differences in risk for presence

of CIN III or worse among women with ASCUS and CIN I in cytology, suggesting

that HPV typing could be useful for further optimization of ASCUS/CIN I triaging

strategies.

In summary, 2 HPV-genotyping methods with different applicability have been

developed and validated. We also conclude that HPV genotyping is useful both in

secondary screening as well as in follow-up after treatment for CIN. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Gyllensten, Ulf, Inst. genetics and pathology, Uppsala university
organization
publishing date
type
Thesis
publication status
published
subject
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2008:116
pages
156 pages
publisher
Department of Medical Microbiology, Lund University
defense location
Pathology lecture hall, UMAS
defense date
2008-12-10 09:00
ISSN
1652-8220
ISBN
978-91-86059-69-9
language
English
LU publication?
yes
id
a18ba084-4c28-438e-9eb0-e88bb34c74ca (old id 1268127)
date added to LUP
2008-11-18 11:48:04
date last changed
2016-09-19 08:44:45
@phdthesis{a18ba084-4c28-438e-9eb0-e88bb34c74ca,
  abstract     = {SUMMARY<br/><br>
Because of the strong causal relationship between persistent infections of human<br/><br>
papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN) and cancer, HPVtesting<br/><br>
has been proposed for improvement of cervical screening programs, including<br/><br>
triaging and follow-up after treatment for CIN. We developed two new methods for<br/><br>
HPV-testing with genotyping: A high-throughput HPV genotyping method that uses<br/><br>
mass spectrometry for detection of the products of type-specific mass extend<br/><br>
reactions, and a method with particularly sensitive detection of a broad spectrum of<br/><br>
HPV-types, also in the case of multiple infections, that uses type-specific probes<br/><br>
coupled to fluorescent beads for detection on the Luminex platform.<br/><br>
The utility of HPV-testing was evaluated in 3 different studies:<br/><br>
A general primer PCR-based genotyping method and the commercial Hybrid Capture<br/><br>
(HCII) assay were compared for sensitivity and specificity for detection of CIN in<br/><br>
secondary screening and in follow-up after treatment for cervical dysplasia. The<br/><br>
sensitivities were high for both methods, although somewhat higher for the PCR<br/><br>
method, but the concordance between the methods was substantial.<br/><br>
The performance of HPV-genotyping for prediction of recurrence after treatment for<br/><br>
CIN was compared to that of cytology. Only HPV-genotyping could predict all cases<br/><br>
of CIN grade II or worse in histopathology, and all cases of CIN I or worse in<br/><br>
cytology during follow-up had persistence of HPV.<br/><br>
The applicability of HPV-genotyping was also evaluated in a secondary screening<br/><br>
setting. Different high-risk HPV types had substantial differences in risk for presence<br/><br>
of CIN III or worse among women with ASCUS and CIN I in cytology, suggesting<br/><br>
that HPV typing could be useful for further optimization of ASCUS/CIN I triaging<br/><br>
strategies.<br/><br>
In summary, 2 HPV-genotyping methods with different applicability have been<br/><br>
developed and validated. We also conclude that HPV genotyping is useful both in<br/><br>
secondary screening as well as in follow-up after treatment for CIN.},
  author       = {Söderlund Strand, Anna},
  isbn         = {978-91-86059-69-9},
  issn         = {1652-8220},
  language     = {eng},
  pages        = {156},
  publisher    = {Department of Medical Microbiology, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Human papillomavirus testing and its application in cervical cancer prevention},
  volume       = {2008:116},
  year         = {2008},
}