AGE-SPECIFIC DISTRIBUTION OF HPV GENOTYPES IN WOMEN FROM THE SOUTHWESTERN REGION OF THE REPUBLIC OF NORTH MACEDONIA

Abstract

Patient age is a well recognised determinant of both the natural history of human papillomavirus infection and the probability of cytological progression, however, the majority of investigations address this relationship only at the level of the broad distinction between single- and multiple-type infection, and the age distribution of individual genotypes remains insufficiently characterised. The present study was undertaken to address this question among HPV-positive women identified through primary cervical screening. The investigation was conducted at the Centre for Public Health Bitola between February 2019 and August 2023. Three hundred women positive for human papillomavirus were tested for twenty-one genotypes by real-time polymerase chain reaction and stratified by cytology into a normal finding, low-risk lesions and high-risk lesions. For each genotype, the mean age of carriers and non-carriers was compared, and the distribution of carriers across five age groups was assessed. Mean age increased significantly with lesion severity, from 31.1 years in the normal group to 35.1 in low-risk and 37.1 in high-risk lesions (p = 0.000112). At the genotype level, statistically significant age signatures were identified. Several genotypes occurred more frequently among the youngest women: type 73 carriers had a mean age of 28.3 years, with 59.1% aged 24 or younger (p < 0.0001); type 82 was likewise more frequent in this age group (54.5% aged ≤ 24; p = 0.0018); and types 59 and 53 also demonstrated significant age structures. In contrast, type 31 carriers were significantly older, and type 68 carriers were over-represented in the 55-to-64 age group (p = 0.012). Type 16 showed a significant age-group distribution (p = 0.04) but no significant difference in mean age, whereas type 18 exhibited no age preference. These reproducible genotype-specific age signatures indicate that certain genotypes behave as transient infections of younger women while others persist into older age. It is recommended that genotype-resolved, age-aware interpretation be incorporated into risk-stratification algorithms and into the determination of screening intervals, so that individual genotypes are weighted according to their age profile and oncogenic potential rather than treated as equivalent. The present analysis is based on results derived from a doctoral dissertation and contributes region-specific data from southwestern North Macedonia, where such genotype-resolved age data have not previously been reported.