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HPV testing, methylation and genotyping in cervical cancer screening and treatment follow-up

Lindroth, Ylva LU (2024) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
HPV testing has a higher sensitivity than cytology for identification of women at risk of cancer. Primary HPV testing was introduced in the organized screening program in Skåne, Sweden in 2017 for women 30 years and older. High-risk HPV E6/E7 mRNA was detected in 7.0% of these women. Primary HPV-screening identified a similar proportion of abnormal cytology (ASCUS+) as cytology-based screening (3.70% vs 3.52%). All co-tested women 40-42 years old, with high-grade
cytology were HPV positive, indicating that primary HPV testing did not miss cases of cervical dysplasia. The introduction of primary HPV screening resulted in a 54% increased follow-up rate.

After treatment of high-grade cervical lesions by conization, persistent... (More)
HPV testing has a higher sensitivity than cytology for identification of women at risk of cancer. Primary HPV testing was introduced in the organized screening program in Skåne, Sweden in 2017 for women 30 years and older. High-risk HPV E6/E7 mRNA was detected in 7.0% of these women. Primary HPV-screening identified a similar proportion of abnormal cytology (ASCUS+) as cytology-based screening (3.70% vs 3.52%). All co-tested women 40-42 years old, with high-grade
cytology were HPV positive, indicating that primary HPV testing did not miss cases of cervical dysplasia. The introduction of primary HPV screening resulted in a 54% increased follow-up rate.

After treatment of high-grade cervical lesions by conization, persistent infection with at least one high-risk HPV type was seen in 16% of the women. Low-risk HPV infections more often persisted after treatment. Testing for high-risk HPV showed high sensitivity (92%) for detection of residual high-grade cytology.

Testing for DNA methylation is a promising alternative to cytology for triage of HPV positive women in the screening. Analysis of DNA methylation of the human genes FAM19A4 and miR124-2 in cytology samples collected up to eight years prior to histologically confirmed severe dysplasia and cancer showed a higher sensitivity than cytology. Screening samples collected within three years from histologically diagnosed cancer were positive for methylation of FAM19A4/miR124-2 in 12/14 (86%) cases, while 13/17 (76%) showed abnormal cytology. However, the methylation test was less sensitive than cytology for detection of precancerous lesions (HSIL and AIS). Approximately one third of samples with normal cytology prior to cancer or severe dysplasia were positive in the methylation assay. Adding methylation analysis to HPV positive samples with normal cytology would thus increase the sensitivity for detection of cancer in the screening program. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Gyllensten, Ulf, Department of Immunology, Genetics and Pathology, Uppsala University
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Cervical cancer screening, Methylation, HPV mRNA, HPV analyses, Screening method
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2024:149
pages
91 pages
publisher
Lund University, Faculty of Medicine
defense location
Segerfalksalen, BMC A10, Sölvegatan 17 i Lund. Join by Zoom: https://lu-se.zoom.us/j/67644898519
defense date
2024-12-06 09:00:00
ISSN
1652-8220
ISBN
978-91-8021-646-3
language
English
LU publication?
yes
id
fe995c9c-ec14-45a2-a39c-91b7e73c7007
date added to LUP
2024-11-07 09:33:38
date last changed
2025-04-04 13:59:30
@phdthesis{fe995c9c-ec14-45a2-a39c-91b7e73c7007,
  abstract     = {{HPV testing has a higher sensitivity than cytology for identification of women at risk of cancer. Primary HPV testing was introduced in the organized screening program in Skåne, Sweden in 2017 for women 30 years and older. High-risk HPV E6/E7 mRNA was detected in 7.0% of these women. Primary HPV-screening identified a similar proportion of abnormal cytology (ASCUS+) as cytology-based screening (3.70% vs 3.52%). All co-tested women 40-42 years old, with high-grade<br/>cytology were HPV positive, indicating that primary HPV testing did not miss cases of cervical dysplasia. The introduction of primary HPV screening resulted in a 54% increased follow-up rate.<br/><br/>After treatment of high-grade cervical lesions by conization, persistent infection with at least one high-risk HPV type was seen in 16% of the women. Low-risk HPV infections more often persisted after treatment. Testing for high-risk HPV showed high sensitivity (92%) for detection of residual high-grade cytology.<br/><br/>Testing for DNA methylation is a promising alternative to cytology for triage of HPV positive women in the screening. Analysis of DNA methylation of the human genes FAM19A4 and miR124-2 in cytology samples collected up to eight years prior to histologically confirmed severe dysplasia and cancer showed a higher sensitivity than cytology. Screening samples collected within three years from histologically diagnosed cancer were positive for methylation of FAM19A4/miR124-2 in 12/14 (86%) cases, while 13/17 (76%) showed abnormal cytology. However, the methylation test was less sensitive than cytology for detection of precancerous lesions (HSIL and AIS). Approximately one third of samples with normal cytology prior to cancer or severe dysplasia were positive in the methylation assay. Adding methylation analysis to HPV positive samples with normal cytology would thus increase the sensitivity for detection of cancer in the screening program.}},
  author       = {{Lindroth, Ylva}},
  isbn         = {{978-91-8021-646-3}},
  issn         = {{1652-8220}},
  keywords     = {{Cervical cancer screening; Methylation; HPV mRNA; HPV analyses; Screening method}},
  language     = {{eng}},
  number       = {{2024:149}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{HPV testing, methylation and genotyping in cervical cancer screening and treatment follow-up}},
  url          = {{https://lup.lub.lu.se/search/files/199217806/Thesis_Ylva_Lindroth.pdf}},
  year         = {{2024}},
}