Doctoral dissertation

Olga Veijalainen: Real-life Experience with the Use of HPV Tests in Cervical Cancer Screening and in Triage of Equivocal Cytological Results

Olga Veijalainen
The primary aim of the doctoral dissertation study of M.D. Olga Veijalainen was to evaluate the performance of implementing primary HPV screening in the detection of precancerous cervical lesions within the regional routine organized cervical screening program in the city of Tampere. The Abbott RealTime (ART) hrHPV DNA test was used as a cervical cancer screening test.

Thanks to an organized system of cytology-based cervical cancer screenings, the incidence and mortality from cervical cancer in Finland has declined significantly since the 1960s. The acknowledgement of the strong causal role of high-risk human papillomavirus (hrHPV) infections in the pathogenesis of cervical cancer and its precursors has led to the development of testing for oncogenic hrHPV types.

HrHPV tests have been successfully studied in triage of minor cytological cervical lesions, in the follow-up after treatment of high-grade cervical lesions and, finally, as a new tool for primary screening of cervical cancer. The change from conventional cytology to HPV- based screening in the population-based cervical screening program is perhaps the biggest single change in the screening program for cervical cancer in Finland.

The last totally conventional cytological screening took place in 2011, and the following year, the primary hrHPV cervical screening program was implemented. The results of the first screening round demonstrated that the introduction of the primary HPV screening did not affect the pattern of attendance between the cytology-based and hrHPV-screened groups. The attendance rate in the last round of cytological screening and in the first round of HPV screening were equal and corresponded to the level of attendance of cervical cancer screenings in Finland (approximately 70%).

In the first year of implementation of primary HPV screening the detection rate of cervical intraepithelial neoplasia grade two or worse (CIN2+) doubled in the HPV- screened population. The detection rate of CIN3+ lesions was also higher in the HPV- screened population, but the difference was not statistically significant.

The first three years of experience confirmed a higher detection rate of both CIN2+ and CIN3+ lesions in comparison with conventional cytology (the Relative Risk (RR) 2.45 (95%CI 1.76-3.41) for CIN2+ and RR 2.70 (95%CI 1.75-4.16) for CIN3+.

During the first years of implementation of HPV screening, the policy to refer all women with persistent HPV infections for colposcopy resulted in a doubling of the rate of colposcopy among HPV-screened women in comparison with cytological screening. However, in the second screening round, the colposcopy rate decreased significantly, by 29%.

The outcome from the second screening round demonstrated a 27% (p = 0.220) decrease of histological HSIL+ lesions, the result was not statistically significant. Nevertheless, the available evidence from randomized controlled trials shows the benefit of primary HPV screening in the reduction of CIN3+ lesions in subsequent screening rounds and the following reduction of morbidity and mortality from cervical cancer.

The high detection rate of potentially non-progressive CIN2+ lesions in our studies led to a high rate of follow-up tests and colposcopies, which risked overdiagnosis and overtreatment. A reliable triage test for HPV-positive women and an optimal screening protocol for women with persistent HPV infections are obviously needed to help avoid the harms of primary HPV screening and to refer for follow-up studies and treatment only women with lesions that have a high cancer potential.

The second aim of the study was to evaluate the real-life performance of hrHPV tests in the triage of women with low-grade squamous intraepithelial lesions (LSIL) and repeat atypical squamous cells of undetermined significance (ASC-US). HrHPV testing turned out to be beneficial in the triage of repeat ASC-US in women ≥30 years old. However, in the case of LSIL, the prevalence of hrHPV infections was high (around 70%), and the specificity of the hrHPV tests used (Hybrid Capture II and ART hrHPV DNA tests) was low (36%), limiting the usefulness of hrHPV testing in triage of LSIL.

The doctoral dissertation of M.D. Olga Veijalainen in the field of medicine titled Real-life Experience with the Use of HPV Tests in Cervical Cancer Screening and in Triage of Equivocal Cytological Results will be publicly examined at the Faculty of Medicine and Health Technology of Tampere University at 12 o'clock on Friday 24 September. The venue is Arvo building Jarmo Visakorpi auditorium, address: Arvo Ylpön katu 34. Docent Maija Jakobsson from University of Helsinki will be the opponent while Professor Emerita Johanna Mäenpää will act as the custos.

 

The event can be followed via remote connection.

The dissertation is available online at
http://urn.fi/URN:ISBN:978-952-03-2070-6

 

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