Comparison of Human Papillomavirus Types 16, 18, and 6 Capsid Antibody Responses Following Incident Infection

Carter, Joseph J.; Koutsky, Laura A.; Hughes, James P.; Lee, Shu Kuang; Kuypers, Jane; Kiviat, Nancy B.; Galloway, Denise A.

doi:10.1086/315498

Cited by 494 publications

(426 citation statements)

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“…In women identified as HPV-16 DNA positive at enrolment, less than half were HPV-16 seropositive at enrolment, consistent with previous studies (Carter et al, 2000). Although an additional 13% of seronegative women at enrolment were subsequently seropositive at follow-up, this could be the result of either HPV-16 infection identified at enrolment or from a subsequent infection (e.g.…”

Section: Discussionsupporting

confidence: 87%

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Determinants of human papillomavirus 16 serological conversion and persistence in a population-based cohort of 10 000 women in Costa Rica

et al. 2004

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Determinants of human papillomavirus (HPV)-16 serological conversion and persistence were assessed in a population-based cohort of 10 049 women in Guanacaste, Costa Rica. Serologic responses to HPV-16 were measured in 7986 women by VLP-based enzymelinked immunosorbent assay at both study enrolment (1993/94) and at 5 -7 years of follow-up. Seropositive women were defined as X5 standard deviations above the mean optical density obtained for studied virgins at enrolment (n ¼ 573). Seroconnversion (n ¼ 409), persistence (n ¼ 675), and clearance (n ¼ 541) were defined based on enrolment and follow-up serology measurements. Age-specific distributions revealed that HPV-16 seroconversion was highest among 18-to 24-year-old women, steadily declining with age; HPV-16 seropersistence was lowest in women 65 þ years. In age-adjusted multivariate logistic regression models, a 10-fold risk increase for HPV-16 seroconversion was associated with HPV-16 DNA detection at enrolment and follow-up; two-fold risk of seroconversion to HPV-16 was associated with increased numbers of lifetime and recent sexual partners and smoking status. Determinants of HPV-16 seropersistence included a 1.5-fold risk increase associated with having one sexual partner during follow-up, former oral contraceptive use, and a 3-fold risk increase associated with HPV-16 DNA detection at both enrolment and follow-up. Higher HPV-16 viral load at enrolment was associated with seroconversion, and higher antibody titres at enrolment were associated with seropersistence. (Ho et al, 1995). Moreover, not all women infected with HPV seroconvert; only about half of all HPV DNA-positive women test positive for corresponding type-specific antibodies using available assays (Kirnbauer et al, 1994;Le Cann et al, 1995). For those women who have seroconverted, however, detection of serum antibodies to HPV capsids is a valid marker of current and past type-specific HPV exposure (Wideroff et al, 1995(Wideroff et al, , 1999Carter et al, 1996;Sasagawa et al, 1998;Touze et al, 2001).We previously reported population-based seroprevalence of HPV-16, -18, -31, and -45 in our 10 000 women population-based study in Costa Rica at enrolment; we confirmed the waning detection of HPV antibodies with age and the determinants of seroprevalence to include increasing lifetime number of sexual partners and smoking (Wang et al, 2003), as similarly reported in other prevalence studies (Stone et al, 2002;Nonnenmacher et al, 2003).To extend our cross-sectional findings, we have now completed HPV-16 serology measurements at a second time point, after 5 -7 years of follow-up. Human papillomavirus 16 was selected because it accounts for the majority of cervical cancers worldwide (Munoz et al, 2003) and is the focus of immunology and vaccinology research (Lowy and Frazer, 2003). To further our understanding of HPV serology in the natural history of cervical cancer, we report here the epidemiologic characteristics and determinants of HPV-16 serologic conversion and persistence in our Guanacaste, Costa ...

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Section: Discussionsupporting

confidence: 87%

“…Although IgG seroconversion against HPV-16 has been reported within 6 -12 months of infection (Wikstrom et al, 1995;Carter et al, 2000), the duration of serologic detection (e.g. being seropositive) remains unclear (Stone et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Determinants of human papillomavirus 16 serological conversion and persistence in a population-based cohort of 10 000 women in Costa Rica

et al. 2004

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“…The population tested in the survey may differ by age in terms of how well they represent their age cohort with respect to HPV infection. Finally, antibody levels are likely to wane over time, as has been suggested in other studies (Carter et al, 2000). The use of seroprevalence data such as these to estimate age-specific infection rates therefore needs to be investigated further, for example by comparing force of infection estimates under different assumptions about waning antibody levels to prevalence data from DNA studies.…”

Section: Discussionmentioning

confidence: 97%

“…Firstly, seroprevalence is likely to underestimate the proportion of women who have had an HPV infection, since other studies have suggested that only 65 -90% of HPV DNA-positive female subjects seroconvert, with differences in estimates depending on factors including the testing systems used, how long HPV DNA persists and whether or not there is progression to disease (Dillner, 1999;Carter et al, 2000). Seroconversion may coincide with DNA detection, or may follow by some months; for example, one study found a delay in seroconversion of 6 -12 months after HPV 16 infection, with type-specific variation seen in the time to seroconversion (Carter et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Prevalence of human papillomavirus antibodies in young female subjects in England

Jit

Vyse²,

Borrow³

et al. 2007

Br J Cancer

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Sera from 1483 female subjects in England aged 10 -29 years were tested. The age-standardised seroprevalence was 10.7% (95% confidence intervals 9.0 -12.3) for human papillomavirus (HPV) 6, 2.7% (1.8 -3.6) for HPV 11, 11.9% (10.2 -13.6) for HPV 16, 4.7% (3.5 -5.8) for HPV 18, Infection with human papillomavirus (HPV) types identified as 'high-risk' is a pre-requisite for developing cervical cancer (Munoz et al, 2003). 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). In individuals who mount a detectable humoral immune response, HPV type-specific serum antibodies are an indicator of past exposure. Testing of blood samples also offers the opportunity to survey different populations.Enzyme-linked immunosorbent assays (ELISAs) utilising viruslike particles have been used successfully for seroprevalence studies in several countries including the USA (Stone et al, 2002) and Sweden (af Geijersstam et al, 1999). We report on the first population-based study of HPV 6, 11, 16 and 18 seroprevalence in England, in 10-to 29-year-old female subjects -the likely target age range for vaccination, but an age range in which little is known about infection rates. MATERIALS AND METHODSSerum specimens were obtained from the Health Protection Agency Sero-Epidemiology Unit collection, consisting of unlinked residual sera submitted to laboratories in England for routine microbiological or biochemical investigations. Sera from immunocompromised individuals and repeat sera from the same individuals were excluded (Osborne et al, 2000).Sera were selected from 1483 women aged 10 -29 years, chosen as most important for informing the design of HPV vaccination programmes in the UK. Sera came from 11 laboratories in England that collected samples in 2002 -2004. About 90 samples were selected for each single year of age in the range 10 -19 years, and about 60 samples for each of the ages 20 -29 years. Samples were tested for specific neutralising antibodies to HPV 6, 11, 16 and 18 by Merck and Co Inc., using a multiplexed competitive Luminex s assay with antibody levels reported in milli-Merck units per millilitre (mMu ml À1 ...

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“…More than 100 HPV types have been identified, and at least 30 have been found in cervical cancers. 1 Given the diversity of HPV types and the largely typespecific immunity after natural infections, [2][3][4] it is important to delineate the prevalence of different HPV types found in cervical cancers so as to guide the selection of vaccine candidates. Most studies on HPV have employed consensus primers with an intention to cover a broad spectrum of HPV types.…”

mentioning

confidence: 99%

Biases in human papillomavirus genotype prevalence assessment associatedwith commonly used consensus primers

Chan

Cheung

Tam

et al. 2005

Intl Journal of Cancer

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Consensus primers targeting human papillomaviruses (HPVs) have biases in sensitivity toward certain HPV types. We applied 3 primer sets (GP51/61, MY09/11, PGMY09/11) in parallel on 120 Chinese cervical cancer specimens. GP51/61 exhibited a poor sensitivity for HPV52, for which the prevalence among squamous cell cervical cancer was underestimated from 14.6% to 0%. The fact that HPV52 should rank second in prevalence among squamous cell cervical carcinoma in Hong Kong could be missed if GP51/61, a worldwide commonly used primer set, was selected for HPV detection. Biases in HPV type-specific sensitivity may result in misprioritization of vaccine candidates. ' 2005 Wiley-Liss, Inc.Key words: human papillomavirus; detection; genotype; vaccine; Chinese; Hong Kong; PCR Cervical cancer is the second most common cancer in women worldwide. Strong and consistent evidence accumulated over the past 2 decades confirms the aetiologic role of human papillomaviruses (HPVs) and provides a strong impetus for developing HPV vaccines to prevent cervical cancer. More than 100 HPV types have been identified, and at least 30 have been found in cervical cancers. 1 Given the diversity of HPV types and the largely typespecific immunity after natural infections, 2-4 it is important to delineate the prevalence of different HPV types found in cervical cancers so as to guide the selection of vaccine candidates. Most studies on HPV have employed consensus primers with an intention to cover a broad spectrum of HPV types. With the more than 10% sequence variation between HPV types, biases in sensitivity of a given primer set toward certain types could happen. In our study, we examined the influence of detection methods on assessing the prevalence of HPVs and thus their priority as cervical cancer vaccine candidates. Material and methodsA total of 120 cervical cancer specimens (105 fresh frozen and 15 paraffin embedded; 89 squamous cell carcinoma, 26 adenocarcinoma, 4 adenosquamous carcinoma and 1 lymphoepitheliod carcinoma) collected from Hong Kong Chinese aged 26-84 years (mean 55 years; SD 13.9) were examined. Total DNA was extracted by the QIAamp DNA mini kit (QIAGEN, Hilden, Germany) and with the quality of extracted preparations confirmed by beta-globin PCR. 5 The clinical materials were collected with a written informed consent. Our study was approved by the local institutional ethics committee, and the human experimentation guidelines of the local institute were followed in the conduct of our study.HPV detection and typing was accomplished by 3 different methods in parallel. In the first method, HPV DNA was amplified by the GP51/61 primers that target an approx. 150 bp fragment of the L1 region. 5,6 The HPV type was identified by direct sequencing of PCR amplicons. In the second method, the MY09/ 11 primers that target an approx. 450 bp fragment of the L1 region was used for PCR. 7,8 HPV type was identified by restriction fragment length polymorphisms (RFLPs) using endonucleases RsaI and DdeI as previously described. 8 Ambiguous RFLPs w...

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Comparison of Human Papillomavirus Types 16, 18, and 6 Capsid Antibody Responses Following Incident Infection

Cited by 494 publications

References 28 publications

Determinants of human papillomavirus 16 serological conversion and persistence in a population-based cohort of 10 000 women in Costa Rica

Determinants of human papillomavirus 16 serological conversion and persistence in a population-based cohort of 10 000 women in Costa Rica

Prevalence of human papillomavirus antibodies in young female subjects in England

Biases in human papillomavirus genotype prevalence assessment associatedwith commonly used consensus primers

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