A Virus-Like Particle Enzyme-Linked Immunosorbent Assay Detects Serum Antibodies in a Majority of Women Infected With Human Papillomavirus Type 16

Kirnbauer, Reinhard; Hubbert, Nancy L.; Wheeler, Cosette M.; Becker, Thomas M.; Lowy, Douglas R.; Schiller, John T.

doi:10.1093/jnci/86.7.494

Cited by 347 publications

(264 citation statements)

References 24 publications

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“…The resulting virus-like particles (VLPs), which appear similar to empty virions, can be used in serological studies to test for type specific immunological responses to viral capsid proteins, although there is evidence that a particular assay may cross react with related HPV subtypes (Combita et al, 2002b). Presence of anti-VLP antibodies is an indicator of past and current infection (Kirnbauer et al, 1994;Le Cann et al, 1995;Wideroff et al, 1995;Dillner et al, 1996). The utility of such assays has been demonstrated in previous studies of anti-HPV-16 antibodies in relation to the risk of cancer of the uterine cervix Dillner et al, 1997;Shah et al, 1997;Vonka et al, 1999;Hisada et al, 2001).…”

Section: Epidemiologymentioning

confidence: 99%

The epidemiology of conjunctival squamous cell carcinoma in Uganda

et al. 2002

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As part of a larger investigation of cancer in Uganda, we conducted a case -control study of conjunctival squamous cell carcinoma in adults presenting at hospitals in Kampala. Participants were interviewed about social and lifestyle factors and had blood tested for antibodies to HIV, . The odds of each factor among 60 people with conjunctival cancer was compared to that among 1214 controls with other cancer sites or types, using odds ratios, estimated with unconditional logistic regression. Conjunctival cancer was associated with HIV infection (OR 10.1, 95% confidence intervals [CI] 5.2 -19.4; P50.001), and was less common in those with a higher personal income (OR 0.4, 95% CI 0.3 -1.2; P50.001). The risk of conjunctival cancer increased with increasing time spent in cultivation and therefore in direct sunlight (w 2 trend=3.9, P=0.05), but decreased with decreasing age at leaving home (w 2 trend=3.9, P=0.05), perhaps reflecting less exposure to sunlight consequent to working in towns, although both results were of borderline statistical significance. To reduce confounding, sexual and reproductive variables were examined among HIV seropositive individuals only. Cases were more likely than controls to report that they had given or received gifts for sex (OR 3.5, 95% CI 1.2 -10.4; P=0.03), but this may have been a chance finding as no other sexual or reproductive variable was associated with conjunctival cancer, including the number of self-reported lifetime sexual partners (P=0.4). The seroprevalence of antibodies against HPV-18 and -45 was too low to make reliable conclusions. The presence of anti-HPV-16 antibodies was not significantly associated with squamous cell carcinoma of the conjunctiva (OR 1.5, 95% CI 0.5 -4.3; P=0.5) and nor were anti-KSHV antibodies (OR 0.9, 95% CI 0.4 -2.1; P=0.8). The 10-fold increased risk of conjunctival cancer in HIV infected individuals is similar to results from other studies. Squamous cell carcinoma of the conjunctiva is thought to be an extreme form of a spectrum of clinical conditions, collectively known as 'ocular surface squamous neoplasias', which range in severity from mild dysplasia, to carcinoma in situ and, ultimately, to invasive carcinoma. Symptoms can range from none, to severe pain and visual loss. Lesions generally arise on exposed areas of the eye, particularly on the nasal side, and treatment involves local excision, or in more severe cases, orbital clearance. Metastases are rare and the prognosis is usually favourable.Although relatively rare everywhere, conjunctival carcinoma is more frequent in parts of sub-Saharan Africa. Uganda offers a good setting in which to investigate the epidemiology of squamous cell carcinoma of the conjunctiva, because the tumour was relatively frequent there, even before the onset of the HIV epidemic (Templeton, 1973;Wabinga et al, 2000). In this report, we examine the association of conjunctival tumours with over 50 possible risk factors, including evidence of infection with HIV-1, HPV-16, -18 and -45 and Kaposi's sarcoma-associa...

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Section: Epidemiologymentioning

confidence: 99%

The epidemiology of conjunctival squamous cell carcinoma in Uganda

et al. 2002

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

Kreimer

Clifford

Snijders

et al. 2005

Intl Journal of Cancer

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A considerable subset of oropharyngeal squamous cell carcinomas (SCCs) are positive for human papillomavirus (HPV); however, delineating etiologically-associated HPV infections from SCCs with concurrent HPV infection unrelated to tumorigenesis is challenging. Viral load assessment in biopsy specimens may help facilitate such differentiation. HPV16 viral load and serologic markers were assessed among oral and oropharyngeal cases from a multinational study conducted by the International Agency for Research on Cancer (IARC). HPV16 viral load, measured semiquantitatively by PCR-enzyme immunoassay, was dichotomized as high or low based on the median optical density value. Serologic antibodies to HPV16 virus-like particles (VLPs) and to HPV16 E6 and E7 proteins were measured by ELISA. Compared to HPV DNA-negative cases (n = 852), HPV16 DNA-positive cases with high viral load (n = 26) were significantly more likely to originate in the oropharynx (odds ratio [OR], 12.0; 95% confidence interval [CI], 5.2-27.5) and, after adjustment for tumor site (AdjOR), have antibodies against HPV16 VLPs (AdjOR, 14.6; 95% CI, 6.0-35.6), E6 (AdjOR, 57.6; 95% CI, 21.4-155.3) and E7 (AdjOR, 25.6; 95% CI, 9.3-70.8). HPV16 DNA-positive cases with low viral load (n = 27) were more commonly oropharyngeal (OR, 2.7; 95% CI, 1.1-6.2) and seropositive for HPV16 VLPs (AdjOR, 2.7; 95% CI, 1.1-6.9), E6 (AdjOR, 3.0; 95% CI, 0.7-14.0) and E7 (AdjOR, 3.5; 95% CI, 0.7-16.3), compared to HPV DNA-negative cases; the associations, however, were neither as strong nor as significant as the associations for high viral load. As there appears to be a strong association between HPV16 serologic markers and viral load, in the absence of data on serologic markers, HPV16 viral load may be used to help delineate the subset of HPV16 DNA-positive oral and oropharyngeal cancers that may be the consequence of HPV infection. ' 2005 Wiley-Liss, Inc.Key words: human papillomavirus; HPV16 viral load; oral cancer; oropharyngeal cancer Numerous studies have provided consistent evidence that human papillomavirus (HPV), the necessary cause of cervical cancer, is present in tumor biopsies from approximately 20-50% of oropharyngeal squamous cell carcinomas (SCCs) and a smaller subset of oral SCCs. 1-4 Among HPV DNA-positive oropharyngeal SCCs, 90% are positive for HPV16. 1-4 Nonetheless, HPV DNA detection in tumor biopsies may not be sufficient evidence of causation. HPV16 DNA from tumor specimens analyzed jointly with markers of expression of the viral oncogene E6, mutational patterns of the cancer suppressor gene TP53 and levels of allelic loss, have helped identify a subset of these cancers that may be the consequence of HPV infection. 1,2,[5][6][7][8] HPV viral load, a measure of the amount of viral DNA in biopsy specimens, alone or in conjunction with well-characterized HPV serologic assays, may clarify the role of HPV among oral and oropharyngeal cases. Antibodies against HPV E6 and E7 are markers of an invasive HPV-associated malignancy 9,10 and are rarely present among ind...

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“…(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).…”

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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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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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A Virus-Like Particle Enzyme-Linked Immunosorbent Assay Detects Serum Antibodies in a Majority of Women Infected With Human Papillomavirus Type 16

Cited by 347 publications

References 24 publications

The epidemiology of conjunctival squamous cell carcinoma in Uganda

The epidemiology of conjunctival squamous cell carcinoma in Uganda

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

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

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