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Penile Intraepithelial Neoplasia and Penile Cancer. Risk Factors and Treatment.

Kristiansen, Sinja LU (2022) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Abstract
Penile cancer and its precursor, penile intraepithelial neoplasia (PeIN), are rare malignancies. Data on risk factors, incidence, and treatment of PeIN is scarce. The prevalence of human papillomavirus (HPV) varies substantially between studies of penile cancer.

The aims of this thesis were to explore the incidence, risk factors and treatment of PeIN; to analyse the prevalence of HPV and skin diseases in circumcised preputium; to investigate the prevalence of HPV in penile cancer compared to age-matched controls; and in HPV16-positive cases, to analyse viral activity.

Risk factors for PeIN, studied in a case-control study of 580 cases and 3436 controls, showed increased odds ratios for lichen sclerosus (LS),... (More)
Abstract
Penile cancer and its precursor, penile intraepithelial neoplasia (PeIN), are rare malignancies. Data on risk factors, incidence, and treatment of PeIN is scarce. The prevalence of human papillomavirus (HPV) varies substantially between studies of penile cancer.

The aims of this thesis were to explore the incidence, risk factors and treatment of PeIN; to analyse the prevalence of HPV and skin diseases in circumcised preputium; to investigate the prevalence of HPV in penile cancer compared to age-matched controls; and in HPV16-positive cases, to analyse viral activity.

Risk factors for PeIN, studied in a case-control study of 580 cases and 3436 controls, showed increased odds ratios for lichen sclerosus (LS), lichen planus (LP), genital warts, balanoposthitis, taking immunosuppressive drugs, penile surgical procedures and organ transplantation.

The incidence of PeIN retrieved from the Swedish National Penile Cancer Register over 20 years, revealed an increased standardised incidence rate of 2.37 from 2019 to 2000. A comparison of given treatment for PeIN in the last five years, compared to the first five years of the period studied, showed surgery to be more common than laser treatment and, topical imiquimod and 5-FU to be more common than local destructive methods.

Analysis of symptomatic foreskin (N=351) showed HPV in 17.1% of cases, high-risk (HR) HPV types in 9.1% with HPV16 in only 2.3%. Histologically, LS, LP and lichenoid dermatitis were seen in 73.5% and PeIN in 2%, despite no clinical suspicion of malignancy.

In penile cancers (N=135) HPV was detected in 38.5% of cases and HPV16 was present in 27.4%. Among cases and age-matched controls (N=105) HR HPV types were found in 34.3% (48/135) of tumours and in 4.8% (5/105) of controls (p<0.001). Among tumours and controls, HPV16 was present in 27.4% (37/135) and 1% (1/105), respectively (p< 0.001). Viral activity (HPV16 mRNA) among HPV16-positive cases was more common in the tumour (86.5%) compared to adjacent to the tumour (21.7%) (p<0.001).

In conclusion, this thesis provides knowledge about risk factors, change in incidence, and treatment methods over 20 years for PeIN. For penile cancer, HR HPV types were significantly more common in penile cancer cases than in age-matched controls. The finding of active HPV16 in penile cancer suggests that HPV16 is an oncogenic driver of the disease. (Less)
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author
supervisor
opponent
  • Professor Paoli, John, Department of Dermatology and Venereology, Sahlgrenska University Hospital, Gothenburg
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Penile intrapithelial neoplasia, PeIN, penile cancer, risk factors, HPV, incidence, histopathology
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2022:45
pages
91 pages
publisher
Lund University, Faculty of Medicine
defense location
Sal U306, Jan Waldenströms gata 25, 3 vån, Malmö universitet, Fakulteten för hälsa och samhälle i Malmö. Join by Zoom: https://lu-se.zoom.us/j/68300665610
defense date
2022-04-01 09:00:00
ISSN
1652-8220
ISBN
978-91-8021-206-9
language
English
LU publication?
yes
id
ad42caa3-cee6-4da5-bc4d-98557373c052
date added to LUP
2022-03-09 08:39:57
date last changed
2022-03-25 08:11:34
@phdthesis{ad42caa3-cee6-4da5-bc4d-98557373c052,
  abstract     = {{Abstract<br/>Penile cancer and its precursor, penile intraepithelial neoplasia (PeIN), are rare malignancies. Data on risk factors, incidence, and treatment of PeIN is scarce. The prevalence of human papillomavirus (HPV) varies substantially between studies of penile cancer.<br/><br/>The aims of this thesis were to explore the incidence, risk factors and treatment of PeIN; to analyse the prevalence of HPV and skin diseases in circumcised preputium; to investigate the prevalence of HPV in penile cancer compared to age-matched controls; and in HPV16-positive cases, to analyse viral activity.<br/><br/>Risk factors for PeIN, studied in a case-control study of 580 cases and 3436 controls, showed increased odds ratios for lichen sclerosus (LS), lichen planus (LP), genital warts, balanoposthitis, taking immunosuppressive drugs, penile surgical procedures and organ transplantation.<br/><br/>The incidence of PeIN retrieved from the Swedish National Penile Cancer Register over 20 years, revealed an increased standardised incidence rate of 2.37 from 2019 to 2000. A comparison of given treatment for PeIN in the last five years, compared to the first five years of the period studied, showed surgery to be more common than laser treatment and, topical imiquimod and 5-FU to be more common than local destructive methods.<br/><br/>Analysis of symptomatic foreskin (N=351) showed HPV in 17.1% of cases, high-risk (HR) HPV types in 9.1% with HPV16 in only 2.3%. Histologically, LS, LP and lichenoid dermatitis were seen in 73.5% and PeIN in 2%, despite no clinical suspicion of malignancy.<br/><br/>In penile cancers (N=135) HPV was detected in 38.5% of cases and HPV16 was present in 27.4%. Among cases and age-matched controls (N=105) HR HPV types were found in 34.3% (48/135) of tumours and in 4.8% (5/105) of controls (p&lt;0.001). Among tumours and controls, HPV16 was present in 27.4% (37/135) and 1% (1/105), respectively (p&lt; 0.001). Viral activity (HPV16 mRNA) among HPV16-positive cases was more common in the tumour (86.5%) compared to adjacent to the tumour (21.7%) (p&lt;0.001).<br/><br/>In conclusion, this thesis provides knowledge about risk factors, change in incidence, and treatment methods over 20 years for PeIN. For penile cancer, HR HPV types were significantly more common in penile cancer cases than in age-matched controls. The finding of active HPV16 in penile cancer suggests that HPV16 is an oncogenic driver of the disease.}},
  author       = {{Kristiansen, Sinja}},
  isbn         = {{978-91-8021-206-9}},
  issn         = {{1652-8220}},
  keywords     = {{Penile intrapithelial neoplasia, PeIN, penile cancer, risk factors, HPV, incidence, histopathology}},
  language     = {{eng}},
  number       = {{2022:45}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Penile Intraepithelial Neoplasia and Penile Cancer. Risk Factors and Treatment.}},
  url          = {{https://lup.lub.lu.se/search/files/115079299/Avhandling_Sinja_Kristiansen_web.pdf}},
  year         = {{2022}},
}