Abstract
Low-grade squamous intraepithelial lesions (LSIL) associated with certain human papillomavirus (HPV) genotypes may preferentially progress to cervical cancer. HPV genotyping may thus have the potential to improve the effectiveness of screening programs and to reduce overtreatment. LSIL cases (n = 8,308) from 55 published studies were included in a meta-analysis. HPV genotype distribution was assessed by geographic region and in comparison with published data on cervical squamous cell carcinoma (SCC). HPV detection in LSIL was 80% in North America but less than 70% in other regions, most likely reflecting regional differences in LSIL diagnosis. Among 5,910 HPV-positive LSILs, HPV16 was the most common genotype (26.3%) followed by HPV31 (11.5%), HPV51 (10.6%), and HPV53 (10.2%). HPV-positive LSILs from Africa were 2-fold less likely to be infected with HPV16 than those in Europe, and HPV-positive LSILs from North America were more likely to be infected with HPV18 than those from Europe or South/Central America. Interpretation for rarer genotypes was hampered by variation in HPV testing methodology. SCC/LSIL prevalence ratios indicated that HPV16 was 2-fold and HPV18 was 1.5-fold more common in SCC than in HPV-positive LSIL, thus appearing more likely to progress than other high-risk genotypes (SCC/LSIL prevalence ratios between 0.05 and 0.85). HPV53 and HPV66 showed SCC/LSIL ratios of 0.02 and 0.01, respectively. HPV genotype distribution in LSIL differs from that in cervical cancer, highlighting the importance of HPV genotype in the risk of progression from LSIL to malignancy. Some regional differences in the relative importance of HPV genotypes in LSIL were noted.
Highlights
About 1.5 million women (2-3% of all those screened for cervical cancer) are diagnosed with low-grade squamous intraepithelial lesions (LSIL) each year in the United States (1)
For the purpose of this analysis, LSIL refers both to lesions cytologically equivalent to LSIL according to the Bethesda system (10) and to lesions histologically confirmed as CIN1 (11)
human papillomavirus genotypes (HPV)-positive LSILs in Africa were 2-fold and significantly less likely to be infected with HPV16 (OR, 0.49; 95% floating CIs (95% FCI), 0.33-0.72) than those in Europe (OR, 1.00; 95% FCI, 0.92-1.09)
Summary
About 1.5 million women (2-3% of all those screened for cervical cancer) are diagnosed with low-grade squamous intraepithelial lesions (LSIL) each year in the United States (1). LSILs are most often managed by colposcopy to confirm underlying cervical intraepithelial neoplasia (CIN) 1 (2). Diagnosis and treatment of LSIL is associated with patient anxiety, morbidity, and cost (3). If left untreated, only a fraction of LSIL progress toward malignancy, with most regressing spontaneously, especially in young women (4). A specific subset of human papillomavirus genotypes (HPV), called high-risk genotypes, has been firmly established as the cause of invasive cervical cancer and its precursor lesions (5). Even high-risk genotypes, may differentially progress from LSIL to malignancy (6), so that HPV genotype may have potential use in separating HPVpositive women at greater risk of cancer from those who can be safely screened at longer intervals. In the era of widespread HPV-based primary screening (7) and HPV-based triage of screen-detected cervical abnormalities (8), this would improve performance and cost-effectiveness of programs while reducing patient anxiety and overtreatment
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