Non-vaccine Human Papillomavirus Types Research Articles

Cross-protection from human papillomavirus 16/18 against types 45 and 31: fact or fancy?

Human papillomavirus (HPV) types 16 and 18 are responsible for approximately 70% of all cervix cancers, followed by HPV types 45 and 31, which represent an additional 10%. In total, there are 15 HPV types that have been associated with the development of cervical cancer [1,2]. HPV vaccination has been shown to be highly effective in preventing precancerous cervical lesions in several large, international, randomized trials [3–6]. A multivalent vaccine to all types of HPV known to cause cervical cancer may be ideal; however, the costs of large international studies may be prohibitive. There is evidence that cross-neutralization occurs, thereby broadening the coverage of the HPV vaccines and increasing the benefits of vaccine to a larger range of infected people. However, this concept remains controversial. This editorial reviews the evidence for cross-protection in current clinical trials, in vitro work and epidemiologic studies. Recently, Paavonen et al. published an interim analysis of a large, randomized, placebo-controlled trial of a HPV 16/18 L1 virus-like particle (VLP) vaccine [6]. While the primary end point was a decrease in high-grade cervical intraepithelial neoplasia (CIN 2+) associated with HPV 16 and 18, a decrease in persistent infections with other nonvaccine HPV types was also noted. This effect is termed ‘cross-protection.’ A decrease in persistent 6-month infections of 59.9 and 36.1% for HPV 45 and 31, respectively, was found, although this effect did not reach statistical significance against 12-month infections. Cross-protection of 31.6 and 46.5% was found for HPV 52 against 6and 12-month infections, respectively. Previous studies with longer follow-up (4.5 years) did not show protection against HPV 52, suggesting that this protective effect

Epidemiology of HPV 16 and Cervical Cancer in Finland and the Potential Impact of Vaccination: Mathematical Modelling Analyses

BackgroundCandidate human papillomavirus (HPV) vaccines have demonstrated almost 90%-100% efficacy in preventing persistent, type-specific HPV infection over 18 mo in clinical trials. If these vaccines go on to demonstrate prevention of precancerous lesions in phase III clinical trials, they will be licensed for public use in the near future. How these vaccines will be used in countries with national cervical cancer screening programmes is an important question.Methods and FindingsWe developed a transmission model of HPV 16 infection and progression to cervical cancer and calibrated it to Finnish HPV 16 seroprevalence over time. The model was used to estimate the transmission probability of the virus, to look at the effect of changes in patterns of sexual behaviour and smoking on age-specific trends in cancer incidence, and to explore the impact of HPV 16 vaccination. We estimated a high per-partnership transmission probability of HPV 16, of 0.6. The modelling analyses showed that changes in sexual behaviour and smoking accounted, in part, for the increase seen in cervical cancer incidence in 35- to 39-y-old women from 1990 to 1999. At both low (10% in opportunistic immunisation) and high (90% in a national immunisation programme) coverage of the adolescent population, vaccinating women and men had little benefit over vaccinating women alone. We estimate that vaccinating 90% of young women before sexual debut has the potential to decrease HPV type-specific (e.g., type 16) cervical cancer incidence by 91%. If older women are more likely to have persistent infections and progress to cancer, then vaccination with a duration of protection of less than 15 y could result in an older susceptible cohort and no decrease in cancer incidence. While vaccination has the potential to significantly reduce type-specific cancer incidence, its combination with screening further improves cancer prevention.ConclusionsHPV vaccination has the potential to significantly decrease HPV type-specific cervical cancer incidence. High vaccine coverage of women alone, sustained over many decades, with a long duration of vaccine-conferred protection, would have the greatest impact on type-specific cancer incidence. This level of coverage could be achieved through national coordinated programmes, with surveillance to detect cancers caused by nonvaccine oncogenic HPV types.