Human papillomavirus (HPV)-related screening technologies and HPV vaccination offer enormous potential for cancer prevention, notably prevention of cervical cancer. However, the effectiveness of these approaches is suboptimal owing to limited implementation of screening programs and restricted indications for HPV vaccination. Trials of HPV vaccination in women aged up to age 55 years have shown almost 90% protection from cervical pre-cancer caused by HPV16/18 among HPV16/18-DNA-negative women. We propose extending routine vaccination programs to women of up to 30 years of age (and to 45–50-year age groups in some settings), paired with at least one HPV-screening test at age 30 years or older. Expanding the indications for HPV vaccination and much greater use of HPV testing in screening programs has potential to accelerate the decline in cervical cancer incidence. Such a combined protocol would represent an attractive approach for many health-care systems, in particular, countries in central and Eastern Europe, Latin America, Asia, and some more-developed parts in Africa. The role of vaccination in women aged >30 years, and the optimal number of HPV-screening tests required in vaccinated women, remain important research issues. Cost-effectiveness models will help determine the optimal combination of HPV vaccination and screening in public health programs, and to estimate the effects of such approaches in different populations.