Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2

Rikke Kamp Damgaard; David Jenkins; Mark H. Stoler; Maurits de Koning; Miekel van de Sandt; Kathrine Dyhr Lycke; Johnny Kahlert; Patti E. Gravitt; Wim G.V. Quint; Torben Steiniche; Lone Kjeld Petersen; Anne Hammer

doi:10.1016/j.ajog.2024.01.029

Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2

Rikke Kamp Damgaard, David Jenkins, Mark H. Stoler, Maurits de Koning, Miekel van de Sandt, Kathrine Dyhr Lycke, Johnny Kahlert, Patti E. Gravitt, Wim G.V. Quint, Torben Steiniche, Lone Kjeld Petersen, Anne Hammer^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

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Abstract

Background: In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression. Objective: This study aimed to describe human papillomavirus HPV type–specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. Study Design: We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF₁₀-DEIA-LiPA₂₅ system (DNA ELISA [enzyme-linked immunosorbent assay] HPV SPF10 kit and RHA HPV SPF10-LiPA25 kit). Persistence/progression was defined as having a record of cervical intraepithelial neoplasia grade ≥2 in the DPDB determined on the last and worst diagnosis on a biopsy or loop electrosurgical excision procedure specimen during follow-up. We estimated the relative risk (95% confidence interval) of persistence/progression using a modified Poisson model. Results: A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37–1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03–1.61), whereas no differences were observed across age groups. Conclusion: The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women.

Originalsprog	Engelsk
Tidsskrift	American Journal of Obstetrics and Gynecology
Vol/bind	230
Nummer	6
Sider (fra-til)	655.e1-655.e10
DOI	https://doi.org/10.1016/j.ajog.2024.01.029 https://doi.org/10.1016/j.ajog.2024.01.029
Status	Udgivet - jun. 2024

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Damgaard 2024 Extended genotyping CIN2Korrektur, 862 KBLicens: CC BY

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Damgaard, R. K., Jenkins, D., Stoler, M. H., de Koning, M., van de Sandt, M., Lycke, K. D., Kahlert, J., Gravitt, P. E., Quint, W. G. V., Steiniche, T., Petersen, L. K., & Hammer, A. (2024). Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. American Journal of Obstetrics and Gynecology, 230(6), 655.e1-655.e10. https://doi.org/10.1016/j.ajog.2024.01.029, https://doi.org/10.1016/j.ajog.2024.01.029

@article{ea7ac51c3f1f4753a26c407e1bcbc347,

title = "Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2",

abstract = "Background: In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression. Objective: This study aimed to describe human papillomavirus HPV type–specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. Study Design: We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF10-DEIA-LiPA25 system (DNA ELISA [enzyme-linked immunosorbent assay] HPV SPF10 kit and RHA HPV SPF10-LiPA25 kit). Persistence/progression was defined as having a record of cervical intraepithelial neoplasia grade ≥2 in the DPDB determined on the last and worst diagnosis on a biopsy or loop electrosurgical excision procedure specimen during follow-up. We estimated the relative risk (95% confidence interval) of persistence/progression using a modified Poisson model. Results: A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37–1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03–1.61), whereas no differences were observed across age groups. Conclusion: The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women.",

keywords = "cervical cancer prevention, cervical intraepithelial neoplasia grade 2, clinical management, human papillomavirus genotyping, risk assessment",

author = "Damgaard, {Rikke Kamp} and David Jenkins and Stoler, {Mark H.} and {de Koning}, Maurits and {van de Sandt}, Miekel and Lycke, {Kathrine Dyhr} and Johnny Kahlert and Gravitt, {Patti E.} and Quint, {Wim G.V.} and Torben Steiniche and Petersen, {Lone Kjeld} and Anne Hammer",

year = "2024",

month = jun,

doi = "10.1016/j.ajog.2024.01.029",

language = "English",

volume = "230",

pages = "655.e1--655.e10",

journal = "American Journal of Obstetrics and Gynecology",

issn = "1097-6868",

publisher = "Mosby, Inc",

number = "6",

}

Damgaard, RK, Jenkins, D, Stoler, MH, de Koning, M, van de Sandt, M, Lycke, KD, Kahlert, J, Gravitt, PE, Quint, WGV, Steiniche, T , Petersen, LK & Hammer, A 2024, 'Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2', American Journal of Obstetrics and Gynecology, bind 230, nr. 6, s. 655.e1-655.e10. https://doi.org/10.1016/j.ajog.2024.01.029, https://doi.org/10.1016/j.ajog.2024.01.029

Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. / Damgaard, Rikke Kamp; Jenkins, David; Stoler, Mark H. et al.
I: American Journal of Obstetrics and Gynecology, Bind 230, Nr. 6, 06.2024, s. 655.e1-655.e10.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2

AU - Damgaard, Rikke Kamp

AU - Jenkins, David

AU - Stoler, Mark H.

AU - de Koning, Maurits

AU - van de Sandt, Miekel

AU - Lycke, Kathrine Dyhr

AU - Kahlert, Johnny

AU - Gravitt, Patti E.

AU - Quint, Wim G.V.

AU - Steiniche, Torben

AU - Petersen, Lone Kjeld

AU - Hammer, Anne

PY - 2024/6

Y1 - 2024/6

N2 - Background: In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression. Objective: This study aimed to describe human papillomavirus HPV type–specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. Study Design: We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF10-DEIA-LiPA25 system (DNA ELISA [enzyme-linked immunosorbent assay] HPV SPF10 kit and RHA HPV SPF10-LiPA25 kit). Persistence/progression was defined as having a record of cervical intraepithelial neoplasia grade ≥2 in the DPDB determined on the last and worst diagnosis on a biopsy or loop electrosurgical excision procedure specimen during follow-up. We estimated the relative risk (95% confidence interval) of persistence/progression using a modified Poisson model. Results: A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37–1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03–1.61), whereas no differences were observed across age groups. Conclusion: The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women.

AB - Background: In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression. Objective: This study aimed to describe human papillomavirus HPV type–specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. Study Design: We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF10-DEIA-LiPA25 system (DNA ELISA [enzyme-linked immunosorbent assay] HPV SPF10 kit and RHA HPV SPF10-LiPA25 kit). Persistence/progression was defined as having a record of cervical intraepithelial neoplasia grade ≥2 in the DPDB determined on the last and worst diagnosis on a biopsy or loop electrosurgical excision procedure specimen during follow-up. We estimated the relative risk (95% confidence interval) of persistence/progression using a modified Poisson model. Results: A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37–1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03–1.61), whereas no differences were observed across age groups. Conclusion: The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women.

KW - cervical cancer prevention

KW - cervical intraepithelial neoplasia grade 2

KW - clinical management

KW - human papillomavirus genotyping

KW - risk assessment

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U2 - 10.1016/j.ajog.2024.01.029

DO - 10.1016/j.ajog.2024.01.029

M3 - Journal article

C2 - 38336125

AN - SCOPUS:85187996475

SN - 1097-6868

VL - 230

SP - 655.e1-655.e10

JO - American Journal of Obstetrics and Gynecology

JF - American Journal of Obstetrics and Gynecology

IS - 6

ER -

Damgaard RK, Jenkins D, Stoler MH, de Koning M, van de Sandt M, Lycke KD et al. Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. American Journal of Obstetrics and Gynecology. 2024 jun.;230(6):655.e1-655.e10. Epub 2024 feb.. doi: 10.1016/j.ajog.2024.01.029, 10.1016/j.ajog.2024.01.029

Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2

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