HPV testing in routine cervical screening: cross sectional data from the ARTISTIC trial

Abstract

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...

Prevalence of human papillomavirus antibodies in young female subjects in England

“…Our results are also consistent with the onset of sexual activity in the UK, as described by a sexual behaviour study in 2000 which found that 50% of women reported sexual debut by age 17 years (Wellings et al, 2001). The results for HPV 16 and 18 in women of ages eligible for cervical screening consistently exceeded the proportion of women found to be HPV DNA positive in a recent study of residual cervical smear samples (Kitchener et al, 2006), as expected for a persistent marker of previous infection.…”

“…The apparent decline in seroprevalence observed around the age of 25 years suggests that seroprevalence is not a straightforward marker of all past HPV infection. Such a marker would be expected to continue to rise in older women, since DNA studies show evidence of incident HPV infections in women of all ages, albeit at a lower rate in older women (Kitchener et al, 2006). There may be several possible explanations for this.…”

“…HPV types 16 and 18 are associated with 70% of cervical cancers worldwide (Munoz et al, 2003), while HPV types 6 and 11, although not 'high-risk', are associated with over 90% of cases of anogenital warts (von Krogh et al, 2001). Two prophylactic vaccines against HPV (a bivalent vaccine against types 16 and 18, and a quadrivalent vaccine that also includes types 6 and 11) have been shown in clinical trials to reduce persistent HPV infection and associated disease by over 90% in up to 5 years of follow-up (Harper et al, 2004;Villa et al, 2006).Epidemiological knowledge of HPV infection in the UK relies heavily on prevalence studies of HPV DNA in the cervical epithelium of women undergoing cervical sampling (Woodman et al, 2001;Kitchener et al, 2006) and usually relates to female subjects known to be sexually active. These studies indicate the prevalence of current infection, as most HPV infections are transient and become DNA negative within 2 years (Moscicki et al, 2006).…”

“…Epidemiological knowledge of HPV infection in the UK relies heavily on prevalence studies of HPV DNA in the cervical epithelium of women undergoing cervical sampling (Woodman et al, 2001;Kitchener et al, 2006) and usually relates to female subjects known to be sexually active. These studies indicate the prevalence of current infection, as most HPV infections are transient and become DNA negative within 2 years (Moscicki et al, 2006).…”

The HPV test has similar sensitivity but more overdiagnosis than the Pap test—A randomised health services study on cervical cancer screening in Finland

“…[1][2][3][4][5] The few follow-up studies have focused on pre-invasive lesions and on the length of reassurance that a negative test provides. [6][7][8][9][10] Only few studies have had emphasis on public health aspects.…”