Persistently high prevalence of HPV16 and Rising Prevalence of Non-16/18 HR-HPV Genotypes in Cervical Precancer and Cancer in Latvia in 2016-2024 Shape the Severity of Cervical Disease

Liba Sokolovska^1*Karina Biserova^1,2Arta Spridzane^1,3Daira Krisane^2,4Alesja Dudorova^1,2Svetlana Gebrila^1,2Ilvija Krasovska⁵Dmitry Perminov⁶Beatrise Orlova⁷Marta Petrovska⁷Juris Jansons^1,8Androniks Mitildzans^1,3Jurijs Nazarovs^10,2,9Maria Isaguliants^1,11*

• ¹Riga Stradins Univeristy, Institute of Microbiology and Virology, Riga, Latvia
• ²Pauls Stradins Clinical University Hospital, Pathology Institute, Riga, Latvia
• ³Riga East Clinical University Hospital, Oncology Centre of Latvia, Riga, Latvia
• ⁴Riga East Clinical Univeristy Hospital, Pathology Centre, Riga, Latvia
• ⁵Riga East Clinical University Hosptial, Oncology Centre of Latvia, Riga, Latvia
• ⁶SIA E Gulbja Laboratorija, Riga, Latvia
• ⁷SIA Centrala Laboratorija, Riga, Latvia
• ⁸Latvijas Biomedicinas petijumu un studiju centrs, Riga, Latvia
• ⁹Riga East Clinical University, Pathology Centre, Riga, Latvia
• ¹⁰Riga Stradins University, Department of Pathology, Riga, Latvia
• ¹¹Karolinska Institutet Institutionen for mikrobiologi tumor- och cellbiologi, Stockholm, Sweden

Cervical cancer incidence and mortality in Latvia is one of the highest in Europe, but data on HR-HPV prevalence in cervical disease are lacking. We aimed to investigate HR-HPV prevalence in cervical squamous cell carcinoma (CSCC) and cervical dysplasia (CD) , association with disease severity, and prevalence changes over time. Cervical tissue samples from 145 patients were retrieved and used for HR-HPV genotyping using two commercially available PCR kits. Only six CD samples were HR-HPV negative (6/66, 9.1%), while all CSCC were positive. Over 50% samples (75/139) harbored one, 33.8% two, 10.1% three, and 2.2% four HR-HPV genotypes. CSCC was more likely to harbor multiple HR-HPVs (p=0.0280). HPV16 remained most prevalent in CSCC and CD and was followed by HPV33 (32/139, 23.0%), HPV39 (13/139, 9.4%), and HPV18 (11/139, 7.9%). CSCC samples were more likely to have high HR-HPV loads (p=0.025). Disease severity expressed as CINI to CSCC grade 3, correlated with HR-HPVs detected (p=0.015, r=0.202) and HPV16 and HPV39 loads (p<0.001, r=0.354; p<0.001, r=0.307). prevalence decreased, insignificantly across the analyzed period, while HPV18 decreased significantly (2016-18: 17.4% vs. 2022-24: 2.2%; p=0.032). HPV66, 45, 39, 31, and 33 (2016-18: 13%; 2022-24:31.1%; p=0.045) increased. HPV16 remained the most prevalent HR-HPV, while HPV18 decreased. Other HR-HPV genotypes (HPV 66/45/39/31/33) demonstrated an increase in prevalence. Cervical disease severity was linked to specific HR-HPV loads and the number infecting HR-HPVs. These findings highlight the need for extended HR-HPV genotyping with determination of viral load, and request more epidemiological studies analyzing historical and current samples.