To evaluate the effectiveness of human papillomavirus (HPV) testing in primary cervical screening. This was a cross-sectional study from the recruitment phase of a prospective randomised trial. Women were screened for HPV in addition to routine cervical cytology testing. Greater Manchester, attendees at routine NHS Cervical Screening Programme. In all, 24 510 women aged 20 -64 screened with liquid-based cytology (LBC) and HPV testing at entry. HPV testing in primary cervical screening. Type-specific HPV prevalence rates are presented in relation to age as well as cytological and histological findings at entry. In all, 24 510 women had adequate cytology and HPV results. Cytology results at entry were: 87% normal, 11% borderline or mild, 1.1% moderate and 0.6% severe dyskaryosis or worse. Prevalence of HPV decreased sharply with age, from 40% at age 20 -24 to 12% at 35 -39 and 7% or less above age 50. It increased with cytological grade, from 10% of normal cytology and 31% of borderline to 70% mild, 86% moderate, and 96% of severe dyskaryosis or worse. HPV 16 or HPV 18 accounted for 64% of infections in women with severe or worse cytology, and one or both were found in 61% of women with severe dyskaryosis but in only 2.2% of those with normal cytology. The majority of young women in Greater Manchester have been infected with a high-risk HPV by the age of 30. HPV testing is practicable as a primary routine screening test, but in women aged under 30 years, this would lead to a substantial increase in retesting and referral rates. HPV 16 and HPV 18 are more predictive of underlying disease, but other HPV types account for 30% of high-grade disease. Cervical cancer is the second most common cancer among women worldwide, and ranks first in many developing countries (Parkin, 2004). Human papillomaviruses (HPV), most frequently HPV 16, are the primary cause of cervical carcinogenesis (IARC, 1995). Over 100 HPV types have now been described, including about 20 'high-risk' types that are associated with cervical cancer (Clifford et al, 2005). The overall prevalence of HPV in cervical cancers in a large international study was over 99%, implying the highest attributable fraction ever identified for a specific cause of a major human cancer (Walboomers et al, 1999). In many developed countries, particularly the UK, systematic cervical screening based on cytology has been responsible for a significant fall in the incidence and death rate from cervical cancer (Peto et al, 2004). The NHS Cervical Screening Programme in England now offers screening 3 yearly between ages 25 and 49 and 5 yearly between 50 and 64 years, and liquid-based cytology (LBC) is currently being implemented. Nonrandomised studies have shown that HPV DNA testing is more sensitive than cytology for detecting CIN, and the International Agency for Research on Cancer (IARC) recently concluded that testing for HPV as a primary screening modality could reduce cancer incidence and mortality (IARC, 2004).In order to evaluate the effectiveness of HPV testing in prima...