These data extend recent molecular and epidemiologic studies and strongly suggest that HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical, and pathologic disease entity that is likely causally associated with HPV infection and that has a markedly improved prognosis.

The prevalence and risk factors for oral human papillomavirus (HPV) infection are unknown, despite evidence for an etiological role for HPV in oral cancers. Oral samples from human immunodeficiency virus (HIV)-seronegative (n=396) and HIV-seropositive (n=190) adults were tested for HPV DNA. High-risk HPV infections were present in 2.1% of tonsil and 6.3% of oral-rinse specimens. The prevalence of oral high-risk HPV infection was greater in HIV-seropositive individuals (13.7% vs. 4.5%; P<.001). In multiple logistic regression, odds of oral HPV infection increased with age, male sex, and herpes simplex virus (HSV)-2 seropositivity in HIV-seronegative individuals and with CD4 cell count <200 cells/mL, HSV-2 seropositivity, oral mucosal abnormalities, and >1 oral sex partner during the previous year (odds ratio, 12.8; 95% confidence interval, 3.1-52.7) among HIV-seropositive individuals. HPV type 16, which is present in most HPV-associated tonsillar cancers, was the most prevalent high-risk oral HPV infection.

Human immunodeficiency virus (HIV) infection and related immunosuppression are associated with excess risk for cervical neoplasia and human papillomavirus (HPV) persistence. Type-specific HPV infection was assessed at 6-month intervals for HIV-positive and HIV-negative women (median follow-up, 2.5 and 2.9 years, respectively). The type-specific incidence of HPV infection was determined, and risk factors for HPV persistence were investigated by statistical methods that accounted for repeated measurements. HIV-positive women were 1.8, 2.1, and 2.7 times more likely to have high-, intermediate-, and low-risk HPV infections, respectively, compared with HIV-negative women. In multivariate analysis, high viral signal, but not viral risk category, was independently associated with persistence among HIV-positive subjects (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-2.9). Furthermore, persistence was 1.9 (95% CI, 1.5-2.3) times greater if the subject had a CD4 cell count <200 cells/microL (vs. >500 cells/microL). Thus, HIV infection and immunosuppression play an important role in modulating the natural history of HPV infection.

Purpose: Persistent infection with oncogenic human papillomaviruses (HPV) plays a central etiologic role in the development of squamous carcinomas of the cervix and their precursor lesions, cervical intraepithelial neoplasias (CIN). We carried out a prospective observational cohort study evaluating known, quantifiable prognostic variables of clinical behavior in women with high-grade cervical lesions. Experimental Design: Our study cohort included healthy women with high-grade cervical lesions (CIN2/3) with residual visible lesions after colposcopically directed biopsy. We prospectively followed 100 women over 15 weeks before standard resection. HPV typing was done using PCR and a reverse line blot detection method. Results: The rate of spontaneous histologic regression, defined as (CIN1 or less at resection) was 28%. The overall rate of HPV infection was 100%. HPV16 was identified in 68% of the lesions. Women with HPV16 only were significantly less likely to regress, compared with women with HPV types other than HPV16 (odds ratio, 0.342; 95% confidence interval, 0.117-0.997; P = 0.049). In the cohort with HPV16 only, patients who had an HLA*A201 allele had similar outcomes to those who did not carryA201. However, among patients with HPV types other than HPV16, the HLA*A201 allele interaction was significant; patients with HLA*A201 were the least likely to resolve. Conclusions: CIN2/3 lesions associated with HPV16 alone are significantly less likely to resolve spontaneously than those caused by other types. Interactions among HPV type, HLA type, and regression rate support a role for HLA-restricted HPV-specific immune responses in determining disease outcome.Persistent infection with a high risk, or oncogenic type of human papillomavirus (HPV) is necessary but not sufficient for the development of most squamous carcinomas of the cervix and their precursor lesions, cervical intraepithelial neoplasia (CIN; ref. 1). CIN1, CIN2, and CIN3 lesions represent a spectrum of disease. Low-grade, or CIN1 lesions, represent a chronic HPV infection, in which HPV DNA is episomal and intact virion production and shedding occur. In women who are immunocompetent, many low-grade, or CIN1 lesions, will nonetheless eventually regress without intervention (1, 2). Reported rates of regression range up to 58% over 24 months (3). A very small percentage (f2%) will progress to high-grade lesions.In contrast, most high-grade, or CIN2/3 lesions are thought to be much more likely to persist than to regress. However, reported rates of spontaneous regression vary from 6% to 50%, depending on diagnostic criteria, and length of follow-up (4). The risk for progression to invasive cancer at 24 months in women with high-grade lesions is f1% to 2%.The mechanisms by which HPV-associated intraepithelial lesions resolve are not well understood. As a prelude to interventional clinical trials in women with biopsy-proven CIN2/3, we carried out a prospective observational cohort study evaluating known, quantifiable prognostic variables in immune ...

Enzyme immunoassays (EIAs) for detection of serum antibodies to simian virus 40 (SV40), BK virus (BKV), and JC virus (JCV) were developed by using virus-like-particles (VLPs) produced in insect cells from recombinant baculoviruses expressing the VP1 protein of the respective virus. Rhesus macaque sera with neutralizing antibodies to SV40 showed a high level of reactivity in the SV40 VLP-based EIA, and these sera also showed lower levels of reactivity in the BKV and JCV VLP-based EIAs. Rhesus macaque sera negative for neutralizing antibodies to SV40 were negative in all three EIAs. Competitive binding assays showed that SV40 VLPs inhibited BKV reactivity. In rhesus macaque sera, high optical density (OD) values for antibodies to SV40 VLPs were correlated with high OD values for antibodies to BKV but not with high OD values for antibodies to JCV VLPs. Human sera with neutralizing antibodies to SV40 were more reactive to SV40 VLPs than human sera without neutralizing antibodies to SV40. The greater SV40 reactivities of human sera were correlated with greater reactivities to BKV VLPs but not JCV VLPs. These data suggest that cross-reactivity with BKV antibodies may account for part of the low-level SV40 reactivity seen in human sera. With their greater versatility and their suitability for large-scale testing, the VLP-based EIAs for SV40, BKV, and JCV are likely to contribute to a better understanding of the biology of these viruses.

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To investigate the role of men in cervical cancer, 816 husbands of women enrolled in four case-control studies of cervical neoplasia in populations at high (Colombia) and low (Spain) risk for cervical cancer were interviewed. Exfoliated cells from the penis were obtained and analyzed by polymerase chain reaction for the presence of human papillomavirus (HPV) DNA. Penile HPV DNA prevalences were higher in husbands of women with cervical neoplasia than in husbands of controls. Husbands of controls in Colombia had a 5-fold higher penile HPV DNA prevalence than the corresponding husbands in Spain. Strong dose-response relationships were found between penile HPV DNA prevalence and all sexual behavior-related variables in Spain but not in Colombia. Sexual promiscuity is the most important risk factor for penile HPV infections. Differences in HPV DNA prevalence in the male populations of Spain and Colombia are consistent with their 8-fold difference in cervical cancer incidences.

BK virus (BKV) and JC virus (JCV) infections were evaluated in a serological study of 496 renal transplant recipients and their donors. A seropositive donor increased the rate of primary and reactivation infections with BKV and of primary infections with JCV. BKV infection rates were not influenced by the source of the renal allograft (cadaver versus living related donor); however, primary JCV infections occurred more often in recipients of seropositive cadaveric kidneys. Reactivated JCV infections occurred less frequently in patients treated with antilymphocyte preparation. BKV and JCV infections in renal transplant recipients may be caused either by reactivation of the recipient's latent virus or by virus from the donor kidney. These infections are, however, not associated with adverse outcome (death, high serum creatinine level, or loss of renal function) in the recipient in the early post-transplant period.