Shift in the high-risk HPV genotypes in cervical precancer and cancer in Latvia from 2016 to 2022, implications for vaccination, screening, and research

Description

Background & Aims:
The most common high-risk HPV (HR-HPV) genotypes associated with cervical cancer and precancer are HPV16 and HPV18. National screening and vaccination campaigns targeting HPV16/18 (Cervarix), then HPV6/11/16/18 (Gardasil) have been ongoing for decades, lately Gardasil 9 was introduced targeting HPV6/11/16/18/31/33/45/52/58. Thanks to active screening and vaccination campaigns, the prevalence of circulating HR HPV genotypes is changing (doi: 10.3389/fcimb.2021.633162; doi.org/10.1186/s12885-018-4033-2; doi: 10.1371/journal.pone.0278477) requesting refocusing of research and health care practices. In Latvia, HPV vaccination campaign was started in 2010 with Cervarix, and continued with Gardasil 9 since 2020. This study aimed to delineate the effect of HPV vaccination on the prevalence of HR HPV genotypes in cervical cancer and precancer in Latvia in 2016-2022.
Materials & Methods:
The study, approved by RSU ethical committee (2-PĒK-4/415/2022, 26/09/2022), was performed using formalin-fixed paraffin-embedded (FFPE) cervical tissue samples from patients with cervical dysplasia and cancer from Pauls Stradiņs Clinical University Hospital repository collected in 2016 (n=10), 2017 (n=12), 2018 (n=9), 2019 (n=8), 2020 (n=7), 2021 and 2022 (n=11). Patient data included age, disease-related metrics, and histological characteristics. The average age was 53 years. Of 68 patients, 23 (33,8%) had cervical dysplasia and 45 (66,2%), cervical cancer with grades 1, 2, or 3 (6,7%, 57,8% and 35,6%, respectively). FFPE blocks were cut into 4-micron sections, 5-11 sections were submerged in 500 μl of sterile mineral oil. Samples were heated to 90°C for 10 min, mineral oil was removed, and DNA isolated using QIAamp DNA FFPE advanced UNG kit (Qiagen). HR HPV genotyping was performed using Anyplex™ II HPV HR Detection kit (Seegene). Changes in HR-HPV positivity over time were analyzed using Fisher's exact test (GraphPad Prism).
Results:
Judging by age, patients were not HPV-vaccinated as by the start of HPV vaccination in Latvia, all were older than 14. All samples were HR-HPV positive, 35 for one (51%), 26 for two (38%), and 7 for three HR HPVs (6%). HPV16 was the most common across the analyzed period, with 83 to 100% being positive. HPV16 positivity in 2016-2019 and 2020-2022 did not differ (p>0.1). HPV18 was rare; of 2016-2019 samples 15%, and of 2020- 2022 samples, 3% tested HPV18+; the decrease was insignificant (p=0,225). Conversely, HPV33 positivity increased from 17 % in 2016-2019 to 82 % in 2020-2023 (p=0,0002). HPV33 was always accompanied by other genotypes, most often HPV16 (15, 22% cases). HPV31, 35, 45, 51, 52, 56, and 66 were detected in single samples (<6% each). Other HR HPVs were not detected. The two patient groups analyzed (2016-2019 and 2020-2022) did not differ in age or diagnosis spectrum (p>0.1).
Discussion:
Although HPV vaccination is available in Latvia since 2010, it has not yet affected the representation of HR HPVs in cervical cancer and precancer. HPV16 remains the main culprit in driving cervical cancer and precancer and should remain in the focus of research and health care. More attention should be paid to other HR HPV genotypes, as HPV33. In 2014, HPV33 was found in 5% of cervical cancer cases (doi: 10.1016/j.virol.2013.10.033). We found it to steady increase since 2019 to up to 80%. Difference in HR HPV genotype distribution in 2016-2019 and 2020-2022 was not related to clinical parameters. Expanded analysis of HPV genotypes in the context of patient data will unravel the role in cervical cancer of HR HPV types other than HPV16, and aid the elucidation of HPV-related disease correlates.

Period	22 Oct 2023 → 24 Oct 2023
Event title	2023 International Society for Vaccines Annual Congress
Event type	Congress
Location	Lausanne, SwitzerlandShow on map
Degree of Recognition	International