Barbara Clayman

Seroreactivity to Human Papillomavirus (HPV) Types 16, 18, or 31 and Risk of Subsequent HPV Infection: Results from a Population-Based Study in Costa Rica

Whether antibodies to human papillomavirus (HPV) capsids, elicited by natural infection, are protective is unknown. This question was addressed in a population-based cohort of 7046 women in Costa Rica by examining the association between baseline seroreactivity to HPV-16, HPV-18, or HPV-31 virus-like particles and the risk of subsequent HPV infection at a follow-up visit 5–7 years after enrollment. Seropositivity to HPV-16, HPV-18, or HPV-31 was not associated with a statistically significant decreased risk of infection with the homologous HPV type [relative risk (RR) and [95% confidence interval (CI)], 0.74 (0.45–1.2), 1.5 (0.83–2.7), and 0.94 (0.48–1.8), respectively]. Seropositivity to HPV-16 or HPV-31 was not associated with a decreased risk of infection with HPV-16 or its genetically related types [RR (95% CI), 0.82 (0.61–1.1) and 0.93 (0.68–1.2), respectively]. Seropositivity to HPV-18 was not associated with a decreased risk of infection with HPV-18 or its genetically related types (RR 1.3; 95% CI 1.0–1.8). Thus, we did not observe immunity, although a protective effect from natural infection cannot be excluded because of the limits of available assays and study designs.

Seroprevalence of human papillomavirus-16, -18, -31, and -45 in a population-based cohort of 10 000 women in Costa Rica

Human papillomavirus (HPV) seroprevalence and determinants of seropositivity were assessed in a 10 049-woman population-based cohort in Guanacaste, Costa Rica. Serologic responses based on VLP-based ELISA were obtained from the plasma collected at study enrollment in 1993/1994 for HPV-16 (n=9949), HPV-18 (n=9928), HPV-31 (n=9932), and HPV-45 (n=3019). Seropositivity was defined as five standard deviations above the mean optical density obtained for studied virgins (n=573). HPV-16, -18, -31, and -45 seroprevalence was 15, 15, 16, and 11%, respectively. Of women DNA-positive for HPV-16, -18, -31, or -45, seropositivity was 45, 34, 51, and 28%, respectively. Peak HPV seroprevalence occurred a decade after DNA prevalence; lifetime number of sexual partners was the key determinant of seropositivity independent of DNA status and age. DNA- and sero-positive women showed the highest risk for concurrent CIN3/cancer, followed by DNA-positive, sero-negative women.

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 (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 enzyme-linked immunosorbent assay at both study enrolment (1993/94) and at 5–7 years of follow-up. Seropositive women were defined as ⩾5 standard deviations above the mean optical density obtained for studied virgins at enrolment (n=573). Seroconnversion (n=409), persistence (n=675), and clearance (n=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+ 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.

Serum Immunoglobulin G Response to Human Papillomavirus Type 16 Virus-Like Particles in Human Immunodeficiency Virus (HIV)–Positive and Risk-Matched HIV-Negative Women

Baseline serum samples from 2815 human immunodeficiency virus (HIV)-positive and 963 HIV-negative women enrolled in 2 cohort studies were tested for immunoglobulin G antibodies to human papillomavirus type 16 (HPV-16) capsids. HPV-16 seropositivity was associated with lifetime number of sex partners (P<.001) among both HIV-positive and HIV-negative women. Approximately 50%-60% of HPV-16 DNA-positive women were HPV-16 positive. HPV-16 seropositivity was associated with HIV infection; however, after adjustment for baseline cervical HPV infection and disease, the association disappeared. Thus, the high seroprevalence of HPV-16 among HIV-positive women may be explained by a high prevalence of HPV of all types. Approximately 50% of HIV-positive women had serological evidence of prior HPV-16 infection, but only approximately 5% had an HPV-16 cervical infection at baseline. Despite the higher prevalence of HPV infection in this group, most HIV-positive women are able to control HPV-16 replication at the cervix, and reactivation, if it occurs, is not very common.

Adeno-associated virus and development of cervical neoplasia

Evidence from several sources has suggested that adeno‐associated virus (AAV) infection might protect against cervical cancer, in part, by interfering with human papillomavirus (HPV)‐induced tumorigenesis. Detection of AAV type 2 (AAV‐2) DNA in cervical tissues has been reported. However, there have been few in vivo studies of women with cervical HPV infection or neoplasia, and these have reported inconsistent results. Therefore, we used polymerase chain reaction (PCR) assays targeted to the AAV‐2rep and cap genes to test tissue specimens from women in an epidemiological study of cervical neoplasia in Jamaica. We tested 105 women with low‐grade cervical intraepithelial neoplasia (CIN‐1), 92 women with CIN‐3/carcinoma in situ or invasive cancer (CIN‐3/CA), and 94 normal subjects. PCR amplification of human β‐globin DNA was found in almost all cervical specimens, indicating that these materials were adequate for PCR testing. The prevalence of HPV DNA, determined by HPV L1 consensus primer PCR was, as expected, strongly associated with presence and grade of neoplasia. Each of the AAV PCR assays detected as few as 10 copies of the virus genome. However, none of the 291 cervical specimens from Jamaican subjects tested positive for AAV DNA. Negative AAV PCR results were also obtained in tests of cervical samples from 79 university students in the United States. Exposure to AAV was assessed further by serology. Using a whole virus AAV‐2 sandwich enzyme‐linked immunosorbent assay, we found no relationship between AAV antibodies and presence or grade of neoplasia in either the Jamaican study subjects or women enrolled in a U.S. cervical cancer case (n = 74) ‐control (n = 77) study. Overall, the data provide no evidence that AAV infection plays a role in cervical tumorigenesis or that AAV commonly infects cervical epithelial cells. J. Med. Virol. 59:60–65, 1999.