Novel diagnostics for improved treatment of gynecological cancer
Keywords:
Gynecological cancer, cervical cancer, ovarian cancer, endometrial cancer, proteomics, biomarkers
Abstract
This paper summarizes the efforts to develop novel biomarkers for diagnosis and screening of the three main gynecological cancers, cervical, endometrial, and ovarian cancer, with an emphasis on research performed during the last 20 years in Uppsala. A cervical cancer screening program has existed in Sweden since 1966 using cytology as the primary test. Over the last two decades, research has provided the scientific base for a transition to self-sampling to improve convenience of the woman and achieve higher population coverage, and use of human papillomavirus as the primary test. Also, efficient prophylactic vaccines and more efficient treatment strategies of women with cervical dysplasia have been introduced. Together, these medical tools have the potential to eradicate cervical cancer by 2120, as envisaged by WHO. By contrast, efficient biomarkers for endometrial and ovarian cancer are still lacking. Through the use of high-throughput proteomics, we have identified novel plasma protein biomarkers to be used in the diagnosis of women with adnexal ovarian mass upon transvaginal ultrasound, and possibly also for early detection in population screening. Similarly, novel biomarkers for the diagnosis of endometrial cancer are being evaluated. To establish a population-based screening program requires careful cost-benefit analyses. One alternative would be to broaden the focus of the current cervical cancer screening program to include also the novel biomarkers for ovarian and endometrial cancer, and thereby achieve screening for all three gynecological cancers. A program that screens for all three diseases could increase motivation to participate and thereby population coverage.
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References
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5. de Lang A, Wikström I, Wilander E. Significance of HPV tests on women with cervical smears showing ASCUS. Acta Obstet Gynecol Scand. 2005;84:1001–5. doi: 10.1111/j.0001-6349.2005.00825.x
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8. Sanner K, Wikström I, Strand A, Lindell M, Wilander E. Self-sampling of the vaginal fluid at home combined with high-risk HPV testing. Br J Cancer. 2009;101:871–4. doi: 10.1038/sj.bjc.6605194
9. Lindell M, Sanner K, Wikström I, Wilander E. Self-sampling of vaginal fluid and high-risk human papillomavirus testing in women aged 50 years or older not attending Papanicolaou smear screening. BJOG. 2012;119:245–8. doi: 10.1111/j.1471-0528.2011.03147.x
10. Wikström I, Lindell M, Sanner K, Wilander E. Self-sampling and HPV testing or ordinary Pap-smear in women not regularly attending screening: a randomised study. Br J Cancer. 2011;105:337–9. doi: 10.1038/bjc.2011.236
11. Josefsson A, Livak K, Gyllensten U. Detection and quantitation of human papillomavirus by using the fluorescent 5’ exonuclease assay. J Clin Microbiol. 1999;37:490–6. doi: 10.1128/JCM.37.3.490-496.1999
12. Ylitalo N, Bergström T, Gyllensten U. Detection of genital human papillomavirus by single-tube nested PCR and type-specific oligonucleotide hybridization. J Clin Microbiol. 1995;33:1822–8. doi: 10.1128/jcm.33.7.1822-1828.1995
13. Moberg M, Gustavsson I, Gyllensten U. Real-time PCR-based system for simultaneous quantification of human papillomavirus types associated with high risk of cervical cancer. J Clin Microbiol. 2003;41:3221–8. doi: 10.1128/JCM.41.7.3221-3228.2003
14. Gustavsson I, Juko-Pecirep I, Backlund I, Wilander E, Gyllensten U. Comparison between the Hybrid Capture 2 and the hpVIR real-time PCR for detection of human papillomavirus in women with ASCUS or low-grade dysplasia. J Clin Virol. 2009;45:85–9. doi: 10.1016/j.jcv.2009.04.012
15. Gustavsson I, Aarnio R, Myrnäs M, Hedlund-Lindberg J, Taku O, Meiring T, et al. Clinical validation of the HPVIR high-risk HPV test on cervical samples applied on the FTA card according to the international guidelines for human papillomavirus DNA test requirements for cervical screening. Virol J. 2019;16:107. doi: 10.1186/s12985-019-1216-7
16. Gustavsson I, Lindell M, Wilander E, Strand A, Gyllensten U. Use of FTA card for dry collection, transportation, and storage of cervical cell specimen to detect high-risk HPV. J Clin Virol. 2009;46:112–6. doi: 10.1016/j.jcv.2009.06.021
17. Gustavsson I, Sanner K, Lindell M, Strand A, Olovsson M, Wikström I, et al. Type-specific detection of high-risk human papillomavirus (HPV) in self-sampled cervicovaginal cells applied to FTA elute cartridge. J Clin Virol. 2011;51:255–8. doi: 10.1016/j.jcv.2011.05.006
18. Maurer K, Luo H, Shen Z, Wang G, Du H, Wang C, et al. Evaluation of a new solid media specimen transport card for high-risk HPV detection and cervical cancer prevention. J Clin Virol. 2016;76:14–9. doi: 10.1016/j.jcv.2015.12.010
19. Catarino R, Vassilakos P, Bilancioni A, Vanden Eynde M, Meyer-Hamme U, Menoud PA, et al. Randomized comparison of two vaginal self-sampling methods for human papillomavirus detection: dry swab versus FTA cartridge. PLoS One. 2015;10:e0143644. doi: 10.1371/journal.pone.0143644
20. Wang SM, Hu SY, Chen W, Chen F, Zhao FH, He W, et al. Feasibility and accuracy evaluation of three human papillomavirus assays for FTA card-based sampling: a pilot study in cervical cancer screening. BMC Cancer. 2015;15:848. doi: 10.1186/s12885-015-1882-9
21. Luo H, Du H, Maurer K, Belinson JL, Wang G, Liu Z, et al. An evaluation of the Cobas4800 HPV test on cervico-vaginal specimens in liquid versus solid transport media. PLoS One. 2016;11:e0148168. doi: 10.1371/journal.pone.0148168
22. Taku O, Meiring TL, Gustavsson I, Phohlo K, Garcia-Jardon M, Mbulawa ZZA, et al. Acceptability of self-collection for human papillomavirus detection in the Eastern Cape, South Africa. PLoS One. 2020;15:e0241781. doi: 10.1371/journal.pone.0241781
23. Gustavsson I, Aarnio R, Berggrund M, Hedlund-Lindberg J, Sanner K, Wikström I, et al. Randomised study of HPV prevalence and detection of CIN2+ in vaginal self-sampling compared to cervical specimens collected by medical personnel. Int J Cancer. 2019;144:89–97. doi: 10.1002/ijc.31637
24. Aarnio R, Isacson I, Sanner K, Gustavsson I, Gyllensten U, Olovsson M. Comparison of vaginal self-sampling and cervical sampling by medical professionals for the detection of HPV and CIN2+: a randomized study. Int J Cancer. 2021;148:3051–9. doi: 10.1002/ijc.33482
25. Sanner K, Wikström I, Gustavsson I, Wilander E, Lindberg JH, Gyllensten U, et al. Daily self-sampling for high-risk human papillomavirus (HR-HPV) testing. J Clin Virol. 2015;73:1–7. doi: 10.1016/j.jcv.2015.09.016
26. Lindström A, Sanchez Hermansson R, Gustavsson I, Hedlund-Lindberg J, Gyllensten U, Olovsson M. Cervical dysplasia in elderly women performing repeated self-sampling for HPV testing. PLoS One. 2018;13:e0207714. doi: 10.1371/journal.pone.0207714
27. Hermansson RS, Olovsson M, Gustavsson I, Gyllensten U, Lindkvist O, Lindberg JH, et al. Incidence of oncogenic HPV and HPV-related dysplasia five years after a negative HPV test by self-sampling in elderly women. Infect Agent Cancer. 2022;17:42. doi: 10.1186/s13027-022-00453
28. Östensson E, Hellström AC, Hellman K, Gustavsson I, Gyllensten U, Wilander E, et al. Projected cost-effectiveness of repeat high-risk human papillomavirus testing using self-collected vaginal samples in the Swedish cervical cancer screening program. Acta Obstet Gynecol Scand. 2013;92:830–40. doi: 10.1111/aogs.12143
29. Aarnio R, Östensson E, Olovsson M, Gustavsson I, Gyllensten U. Cost-effectiveness analysis of repeated self-sampling for HPV testing in primary cervical screening: a randomized study. BMC Cancer. 2020;20:645. doi: 10.1186/s12885-020-07085-9
30. Ylitalo N, Sørensen P, Josefsson AM, Magnusson PK, Andersen PK, Pontén J, et al. Consistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ: a nested case-control study. Lancet. 2000;355:2194–8. doi: 10.1016/S0140-6736(00)02402-8
31. Josefsson AM, Magnusson PK, Ylitalo N, Sørensen P, Qwarforth-Tubbin P, Andersen PK, et al. Viral load of human papilloma virus 16 as a determinant for development of cervical carcinoma in situ: a nested case-control study. Lancet. 2000;355:2189–93. doi: 10.1016/S0140-6736(00)02401-6
32. Berggrund M, Gustavsson I, Aarnio R, Hedlund-Lindberg J, Sanner K, Wikström I, et al. HPV viral load in self-collected vaginal fluid samples as a predictor for the presence of cervical intraepithelial neoplasia. Virol J. 2019;16:146. doi: 10.1186/s12985-019-1253-2
33. Gyllensten U, Sanner K, Gustavsson I, Lindell M, Wikström I, Wilander E. Short-time repeat high-risk HPV testing by self-sampling for screening of cervical cancer. Br J Cancer. 2011;105:694–7. doi: 10.1038/bjc.2011.277
34. Gustavsson I, Aarnio R, Berggrund M, Hedlund-Lindberg J, Strand AS, Sanner K, et al. Randomised study shows that repeated self-sampling and HPV test has more than twofold higher detection rate of women with CIN2+ histology than Pap smear cytology. Br J Cancer. 2018;118:56–64. doi: 10.1038/bjc.2017.485
35. World Health Organization. Self-care interventions for health: WHO consolidated guideline. Available from: https://www.who.int/publications/i/item/WHO-SRH-23.1 [cited 17 April 2023].
36. Bruni L, Serrano B, Roura E, Alemany L, Cowan M, Herrero R, et al. Cervical cancer screening programmes and age-specific coverage estimates for 202 countries and territories worldwide: a review and synthetic analysis. Lancet. 2022;10:e1115–27. doi: 10.1016/S2214-109X(23)00240-1
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Published
2025-02-14
How to Cite
Gyllensten U. (2025). Novel diagnostics for improved treatment of gynecological cancer. Upsala Journal of Medical Sciences, 130, e12111. https://doi.org/10.48101/ujms.v130.12111
Section
Review Articles
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