The Natural History of Human Papillomavirus Type 16 Capsid Antibodies among a Cohort of University Women

Abstract

To study the temporal relationship between serum antibody response and human papillomavirus type 16 (HPV-16) infection, a cohort of 325 university women were scheduled for examinations at 4-month intervals. At every examination, interviews were completed, cells were obtained for polymerase chain reaction-based testing and for Pap screening, and serum was obtained for testing with a HPV-16 capsid-capture ELISA. Seroreactivity was associated with detection of HPV-16 DNA and with increased numbers of sex partners. The median time to seroconversion was 8.3 months among women with incident HPV-16 infections. Within 16 months following HPV-16 DNA detection, 93.7% of women with prevalent and 67.1% of women with incident infections seroconverted. After seroconversion, antibody responses were maintained during follow-up among HPV-16 DNA-positive women. Women who seroconverted were 5.7 times (95% confidence interval = 2.4-13.4) more likely to have squamous intraepithelial lesions associated with the detection of HPV-16 DNA than were women who did not seroconvert.

HPV16 semiquantitative viral load and serologic biomarkers in oral and oropharyngeal squamous cell carcinomas

“…These associations suggest that VLP seropositivity, a marker of past HPV infection, [11][12][13][14][15] rather than HPV-associated tumorigenesis, may actually be the result of HPV exposure that preceded, and possibly contributed to, HPV-related carcinogenesis. More importantly, seropositivities for HPV16 E6 or E7, recognized markers of an HPVassociated malignancy, 9,10 were remarkably higher among cases with high viral load compared to HPV DNA-negative cases.…”

“…Antibodies against HPV E6 and E7 are markers of an invasive HPV-associated malignancy 9,10 and are rarely present among individuals with HPV DNA-negative oral and oropharyngeal tumors. 1 Antibodies against HPV virus-like particles (VLPs) are considered a marker of cumulative, lifetime HPV infection, [11][12][13][14][15] and are associated with HPV-related disease, but not as strongly as E6 and E7 antibodies. While these markers do not allow for inferences on causality, evaluation of the associations between high and low viral load with HPV16 serologic markers among HPV16 DNA-positive and -negative oral and oropharyngeal SCCs may delineate the subset more likely the result of HPV infection.…”

A prospective study of the relationship between prediagnostic Human Papillomavirus seropositivity and HPV DNA in subsequent cervical carcinomas

“…However, a series of validation studies have concluded that only about 50 -70% of genitally infected women (as determined by PCR) will seroconvert (Kirnbauer et al, 1994;Carter et al, 1996;Kjellberg et al, 1999). The reason why HPV serology is not very sensitive for detection of HPV infection is not known.…”

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

“…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).…”

“…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).…”