Human papillomavirus type 18 and rapidly progressing cervical intraepithelial neoplasia

Background Human papillomavirus type 18 (HPV-18) is the second most frequent of the HPV types detected when squamous-cell cancer is diagnosed and the type most strongly associated with adenocarcinoma of the cervix. However, in cross-sectional studies, HPV-18 is rarely detected at the time of diagnosis of high-grade cervical intraepithelial neoplasia (CIN). We used a longitudinal study design to describe the occurrence of cytological abnormality after incident HPV-18 and HPV-16 infections. Methods The analysis was based on 1075 women aged 15–19 years, who had normal cytology and were negative for HPV at recruitment from a single family-planning clinic, and who had further follow-up. The women reattended every 6 months, and samples were taken for cytological and virological examination. Findings The relative risk of a cytological diagnosis of borderline nuclear abnormality after exposure to HPV-18 was 2•06 (95% CI 1•24–3•43) and that after exposure to HPV-16 was 1•99 (1•32–3•01). The relative risks of mild dyskaryosis were 3•11 (1•86–5•18) and 4•76 (3•15–7•18), and the relative risks of moderate or severe dyskaryosis were 0•80 (0•24–2•65) and 2•85 (1•36–5•97). Time to acquisition of cytological abnormality was unrelated to the infecting type (p=0•88). Interpretation Our findings do not support the long-held view that the reason why HPV-18 infection is under-represented at the time of diagnosis of high-grade CIN is because HPV-18-associated disease rapidly progresses through the preinvasive stages of neoplasia. We suggest that the cytological changes detected after HPV-18 infection might understate the severity of underlying disease. This feature could compromise the effectiveness of screening programmes in reducing the frequency of HPV-18-associated cancers.