Management of women who test positive for high-risk types of human papillomavirus: the HART study

Cuzick, Jack; Szarewski, Anne; Cubie, Heather; Hulman, G.; Kitchener, Henry C; Luesley, David; McGoogan, E; Menon, Usha; Terry, George; Edwards, Robert P.; Brooks, Claire; Desai, Mina; Gie, C; Ho, Linda; Jacobs, Ian; Pickles, C; Sasieni, Peter

doi:10.1016/s0140-6736(03)14955-0

Cited by 481 publications

(467 citation statements)

References 18 publications

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“…HPV prevalence in the HART study declined from 14.5% in women aged 30 -34 years to 3.8% in women aged 55 -59 years (Cuzick et al, 2003); the corresponding rates in our cohort were 18.5% at 30 -34 years and 6% at 55 -59 years. Our higher rates may be partly due to regional differences in the UK (2004).…”

Section: Discussioncontrasting

confidence: 50%

“…Primary screening with HPV testing in combination with cytology triage has been recommended only in women aged over 30 years (Sasieni and Cuzick, 2002;Cuzick et al, 2003), as HPV is so common in younger women. This conclusion seems questionable in the light of our results as high-grade dysplasia is as common among HPV-infected women aged under 30 years as in those age 30 -49 years, and much commoner than in women aged over 50 years.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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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...

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Section: Discussioncontrasting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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“…Follow-up studies of women with negative cytology, according to HPV status, are therefore important. In this issue, Bulkmans et al (2005) and Grainge et al (2005), using two different study designs, provide further evidence of the value of adding HPV testing to cervical cytology in screening programmes.In their 5-year cohort study in The Netherlands of 2810 women aged 30 -60 years with normal cytology, Bulkmans et al (2005) show that, in agreement with previous findings from the US (Sherman et al, 2003), France (Clavel et al, 2004) and the UK (Cuzick et al, 2003;Peto et al, 2004), HR HPV testing combined with cytology has higher sensitivity and higher negative predictive value for cervical intraepithelial neoplasia (CIN) 3 and cancer than cytology alone. Specificity was, however, slightly lower for HPV testing and cytology (93%) than cytology alone (95%).…”

supporting

confidence: 69%

“…In their 5-year cohort study in The Netherlands of 2810 women aged 30 -60 years with normal cytology, Bulkmans et al (2005) show that, in agreement with previous findings from the US (Sherman et al, 2003), France (Clavel et al, 2004) and the UK (Cuzick et al, 2003;Peto et al, 2004), HR HPV testing combined with cytology has higher sensitivity and higher negative predictive value for cervical intraepithelial neoplasia (CIN) 3 and cancer than cytology alone. Specificity was, however, slightly lower for HPV testing and cytology (93%) than cytology alone (95%).…”

supporting

confidence: 69%

Human papillomavirus testing in cervical cancer screening

Franceschi

Mahé

2005

Br J Cancer

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Research on the use of human papillomavirus (HPV) DNA testing in the screening and management (triage) of cervical lesions began in the late 1980s with the growing evidence that certain (high-risk (HR)) HPV types were the cause of cervical cancer IARC, 2005). Since women not infected with HR HPV types, even with abnormal cytology, are at negligible risk for cervical cancer, HPV testing could be superior to cytology in cervical cancer screening (Cuzick et al, 1999;Nobbenhuis et al, 1999). Human papillomavirus testing may also be cost-effective if it allows for a longer screening interval, or for screening to be discontinued at an earlier age than currently recommended (i.e., 65 years). Follow-up studies of women with negative cytology, according to HPV status, are therefore important. In this issue, Bulkmans et al (2005) and Grainge et al (2005), using two different study designs, provide further evidence of the value of adding HPV testing to cervical cytology in screening programmes.In their 5-year cohort study in The Netherlands of 2810 women aged 30 -60 years with normal cytology, Bulkmans et al (2005) show that, in agreement with previous findings from the US (Sherman et al, 2003), France (Clavel et al, 2004) and the UK (Cuzick et al, 2003;Peto et al, 2004), HR HPV testing combined with cytology has higher sensitivity and higher negative predictive value for cervical intraepithelial neoplasia (CIN) 3 and cancer than cytology alone. Specificity was, however, slightly lower for HPV testing and cytology (93%) than cytology alone (95%).The improvement in sensitivity and negative predictive value made possible by the addition of HR HPV testing to cytology supports the use of viral testing in order to increase the screening interval, although the findings of Bulkmans et al (2005) should be interpreted with some caution as their study was relatively small, and, as the authors emphasise, an increased sensitivity is implicit in performing any additional test (Franco and Ferenczy, 1999).Also in this issue, Grainge et al (2005) report the findings of a nested case -control study based on women with a normal cytological smear between 1988 and 1992 (termed the baseline smear) who later, after an average of 6.8 years, received a histologically confirmed diagnosis of CIN 2 or worse. Excluding CIN2, which is biologically and clinically difficult to distinguish from CIN1, there were 346 CIN3 cases and 51 cervical cancer cases together with 591 control women who never had cytological abnormalities. Although Grainge et al (2005) found a significantly higher HPV positivity among cases compared to controls, a substantial proportion of women tested negative for HPVs in baseline smears less than 4 years (67%), and 4 -13 years (74%), before the diagnosis of CIN3/cervical cancer. Unfortunately, such use of long-stored archived cervical smears is prone to the danger of false-negative HPV findings (De Roda, 1995) and crosscontamination (Chua and Hjerpe, 1995).It is important to bear in mind, however, that the detection of HPV at a sin...

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“…Seventeen thousand six-hundred and twenty-two women aged [16][17][18][19][20][21][22][23][24][25][26] were enrolled in 1 of 2 randomized, placebo-controlled, efficacy trials (Protocols 013 and 015). Vaccine or placebo was given at day 1, month 2 and 6.…”

mentioning

confidence: 99%

Impact of an HPV6/11/16/18 L1 virus‐like particle vaccine on progression to cervical intraepithelial neoplasia in seropositive women with HPV16/18 infection

Haupt¹,

Wheeler²,

Brown

et al. 2011

Intl Journal of Cancer

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The impact of a human papillomavirus (HPV) vaccine on development of cervical intraepithelial neoplasia grade 2‐3 or adenocarcinoma in situ (CIN2‐3/AIS) in women with ongoing HPV16 or 18 infections prevaccination is reported. Seventeen thousand six‐hundred and twenty‐two women aged 16–26 were enrolled in 1 of 2 randomized, placebo‐controlled, efficacy trials (Protocols 013 and 015). Vaccine or placebo was given at day 1, month 2 and 6. Women were tested for HPV6/11/16/18 DNA and antibodies at day 1. We focus on the subset of women who were seropositive and DNA positive to HPV16 or HPV18 prevaccination. Incidence is expressed as the number of women with an endpoint per 100 person‐years‐at‐risk. In total, 419 vaccine and 446 placebo recipients were both seropositive and DNA positive to HPV16 or HPV18 prevaccination and had at least one follow‐up visit. In Protocol 013, the incidence of HPV16/18‐related CIN2‐3/AIS among these women was 10.9 in the vaccine arm and 7.0 in the placebo arm (vaccine efficacy = −54.9; 95% CI: −181.7, 13.0). In Protocol 015, the incidence of HPV16/18‐related CIN2‐3/AIS was 5.5 in the vaccine arm and 6.2 in the placebo arm (vaccine efficacy = 12.2%; 95% CI: −29.8, 40.9). These data suggest HPV vaccination neither reduces nor enhances progression to HPV16/18‐related high grade cervical lesions, and cervical cytology screening and corresponding management should continue as per local recommendations. Ultimately, population‐based surveillance of vaccinated individuals beyond these clinical trials will be required to further address questions regarding the impact of vaccination in women exposed to vaccine HPV types before vaccination.

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Management of women who test positive for high-risk types of human papillomavirus: the HART study

Cited by 481 publications

References 18 publications

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

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

Human papillomavirus testing in cervical cancer screening

Impact of an HPV6/11/16/18 L1 virus‐like particle vaccine on progression to cervical intraepithelial neoplasia in seropositive women with HPV16/18 infection

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