Sustained efficacy up to 4·5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial

Harper, Diane M.; Franco, Eduardo L.; Wheeler, Cosette M.; Moscicki, Anna‐Barbara; Romanowski, Barbara; Roteli-Martins, Cecília Maria; Jenkins, David; Schuind, Anne; Clemens, Sue Ann Costa; Dubin, Gary

doi:10.1016/s0140-6736(06)68439-0

Cited by 1,390 publications

(1,117 citation statements)

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“…The HPV type might be used to determine whether to refer for colposcopy immediately, repeat the test, or defer any investigation until the next routine screen 3 years later. With the prospect of type 16/18 specific HPV prophylactic vaccines becoming available, data on these types in the screened population is of considerable importance in terms of what proportion of current abnormalities may still occur, notwithstanding a degree of cross protection reported for HPV 45 (Harper et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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

et al. 2006

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“…Types 31 and 45 are of interest because vaccination against 16/18 may result in partial immunity for 31 and 45 through cross-protection (Harper et al, 2006). Within the group of screening-eligible hrHPV-positive women, we estimated the type distribution of HPV16, 18, 31, 45 vs other types.…”

Section: Methodsmentioning

confidence: 99%

“…The results from the current study give an impression of the potential benefits that can be achieved from HPV16/18 vaccination. They can also be used to gain insight into the effects of partial cross-protection against HPV types 31 and 45 (Harper et al, 2006). Furthermore, the figures will serve as inputs for simulation models in which different vaccination and screening strategies will be compared.…”

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confidence: 99%

“…Prophylactic vaccines are now available that are effective against incident and persistent HPV16 and 18 infections (Koutsky et al, 2002;Munoz et al, 2003;Harper et al, 2006;Villa et al, 2006). Mass vaccination can have a substantial impact on the cervical cancer incidence, even in developed countries where the incidence is already low because of implementation of organised cervical screening.…”

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confidence: 99%

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Age-dependent prevalence of 14 high-risk HPV types in the Netherlands: implications for prophylactic vaccination and screening

et al. 2008

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We determined the prevalence of type-specific hrHPV infections in the Netherlands on cervical scrapes of 45 362 women aged 18 -65 years. The overall hrHPV prevalence peaked at the age of 22 with peak prevalence of 24%. Each of the 14 hrHPV types decreased significantly with age (P-values between 0.0009 and 0.03). The proportion of HPV16 in hrHPV-positive infections also decreased with age (OR ¼ 0.76 (10-year scale), 95% CI ¼ 0.67 -0.85), and a similar trend was observed for HPV16 when selecting hrHPV-positive women with cervical intraepithelial neoplasia grade 2 or worse (CIN2 þ ) (OR ¼ 0.76, 95% CI ¼ 0.56 -1.01). In women eligible for routine screening (age 29 -61 years) with confirmed CIN2 þ , 65% was infected with HPV16 and/or HPV18. When HPV16/18-positive infections in women eligible for routine screening were discarded, the positive predictive value of cytology for the detection of CIN2 þ decreased from 27 to 15%, the positive predictive value of hrHPV testing decreased from 26 to 15%, and the predictive value of a double-positive test (positive HPV test and a positive cytology) decreased from 54 to 41%. In women vaccinated against HPV16/18, screening remains important to detect cervical lesions caused by non-HPV16/18 types. To maintain a high-positive predictive value, screening algorithms must be carefully re-evaluated with regard to the screening modalities and length of the screening interval. British Journal of Cancer (2008) . Prophylactic vaccines are now available that are effective against incident and persistent HPV16 and 18 infections (Koutsky et al, 2002;Munoz et al, 2003;Harper et al, 2006; Villa et al, 2006). Mass vaccination can have a substantial impact on the cervical cancer incidence, even in developed countries where the incidence is already low because of implementation of organised cervical screening. To make a well-judged decision about the future role of both vaccination and screening in cervical cancer prevention, detailed information about type-specific hrHPV distribution is required. Data on hrHPV prevalence and type distribution in the Netherlands have been reported previously, but only for a relatively small cohort of 3305 women (Jacobs et al, 2000a;Clifford et al, 2005). To obtain reliable estimates of the hrHPV type distribution in relation to age, both for women with normal and for women with abnormal cytology, data from a far larger cohort are needed. In this study, we determined the age-dependent prevalence of 14 hrHPV types and the age-dependent type distribution within hrHPV-positive women from a cohort of 45 362 women in the Netherlands aged 18 -65 years. The results from the current study give an impression of the potential benefits that can be achieved from HPV16/18 vaccination. They can also be used to gain insight into the effects of partial cross-protection against HPV types 31 and 45 (Harper et al, 2006). Furthermore, the figures will serve as inputs for simulation models in which different vaccination and screening strategies will be compared. MATERIALS AND METHOD...

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“…Nonetheless, some women in the population for whom the vaccines are approved will have been exposed to vaccine HPV types through sexual activity before vaccination. 5,6 Though there have been extensive data published on the efficacy of both vaccines, [7][8][9][10][11][12][13][14][15] less is known about the impact of HPV vaccination in women with ongoing HPV16 or 18 infections. Adequate knowledge of the HPV vaccines' impact on such women has important clinical implications, particularly with respect to HPV16 and HPV18, as several studies have shown that women who are persistently or chronically infected with cervical HPV16 or HPV18 are at considerably higher risk for developing high grade cervical lesions and cancer, compared with women positive for non-HPV16/18 oncogenic types, oncogenic HPV-negative women, or those transiently infected with HPV16/18.…”

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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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Sustained efficacy up to 4·5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial

Cited by 1,390 publications

References 22 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

Age-dependent prevalence of 14 high-risk HPV types in the Netherlands: implications for prophylactic vaccination and 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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