This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Clifford, G. M. Articles by Franceschi, S. Search for Related Content PubMed PubMed Citation Articles by Clifford, G. M. Articles by Franceschi, S.

Serologic Response to Oncogenic Human Papillomavirus Types in Male and Female University Students in Busan, South Korea

¹ International Agency for Research on Cancer, Lyon, France; ² Research Institute for National Cancer Control and Evaluation, National Cancer Centre, Goyang, Republic of Korea; ³ Research Program Infection and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany; and ⁴ DDL Diagnostic Laboratory, Voorburg, the Netherlands

Requests for reprints: Hai-Rim Shin, IARC, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France. Phone: 33-4-72-73-84-18; Fax: 33-4-72-73-80-22. E-mail: shinhr{at}iarc.fr

	Abstract

Top Abstract Introduction Subjects, Materials, and Methods Results Discussion References

 
In the absence of genital samples, human papillomavirus (HPV) serology may be useful to assess HPV infection in young men and women. HPV seroprevalence and determinants of seropositivity were assessed in 817 female and 518 male university students in Busan, South Korea, of whom 74% and 44%, respectively, reported never having had penetrative sexual intercourse. Type-specific HPV DNA status, assessed by a short PCR fragment primer set, was available from genital samples. Seropositivity to L1 proteins of HPV types 16, 18, 31, 33, 45, 52, and 58 were assessed using multiplex HPV serology. Among women, HPV seroprevalence was significantly higher among sexually active (26.1%) than nonsexually active students [11.1%, odds ratio (OR) = 2.9; 95% confidence interval (95% CI), 1.8-4.7], although the association was weaker than that for HPV DNA prevalence (OR, 14; 95% CI, 4.7-42). Furthermore, HPV seroprevalence was higher among HPV DNA-positive (24%) than HPV DNA-negative women (13%), and there was a positive correlation of type-specific seroprevalence with the presence of HPV DNA of the same type. In contrast, HPV seropositivity among men was not associated with sexual behavior or the presence of HPV DNA. Seroprevalence correlates with genital HPV exposure in young women, but its meaning in young men is unclear. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1874–9)

	Introduction

Top Abstract Introduction Subjects, Materials, and Methods Results Discussion References

 
Human papillomavirus (HPV) DNA detection gives a measure of HPV infection at a given anatomic site, most commonly the female cervix. However, it underestimates cumulative exposure because most HPV infections are transient (1). The value of HPV DNA detection as an epidemiologic tool is also limited by sampling difficulties in men (2) and by the unwillingness of many unmarried women to undergo gynecologic examination necessary for the collection of exfoliated cells (3, 4).

HPV antibody response among women, on the other hand, has shown to be a useful epidemiologic marker of cumulative sexual exposure to HPV, being consistently linked to sexual debut, lifetime number of sexual partners, marital status, and herpes simplex virus type 2 seropositivity (5-16), as well as risk of cervical neoplasia/cancer (5, 7, 15, 17-21). Seroconversion is also linked to persistent HPV DNA infection (1, 14, 22), although no more than half of women infected with HPV seem to seroconvert (1, 7, 22, 23).

Seroprevalence data in men are far fewer and less consistent, but the limited data suggest that men are even less likely to mount a detectable antibody response than women (12, 24).

We report on HPV seroprevalence from a cross-sectional survey of female and male students aged 15 to 29 from Busan, South Korea (3), many of whom reported not, or only recently, to have initiated penetrative sexual intercourse. HPV DNA data was obtained from self-collected vaginal cells for women, and physician-collected genital cells for men (3). As major objectives in this report, we assess the gender-specific association of sexual behavior and genital HPV DNA status with seroprevalence of the seven most common HPV types in cervical cancer, detected simultaneously with a novel multiplex HPV antibody assay (25).

	Subjects, Materials, and Methods

Top Abstract Introduction Subjects, Materials, and Methods Results Discussion References

 
Study Procedures
The present survey was conducted during 2002 in three institutions of higher education in Busan, South Korea, the extensive details of which have been published previously (3). In summary, 1,500 students (900 women and 600 men), aged 15 to 29, were asked to complete a self-administered questionnaire including sociodemographic and lifestyle questions [e.g., smoking habits, alcohol consumption, and circumcision (male students only)]. Students were also asked to report whether they had engaged in penetrative sexual intercourse, their lifetime number of sexual partners, and use of contraceptive methods. Of those contacted, 860 female (95.6%) and 541 male (90.2%) students agreed to participate. Each returned, in a sealed envelope, the anonymous questionnaire. All participants signed an informed consent form, which, together with the study protocol, was approved by the ethical review committees of the National Cancer Center, Korea, and of the IARC.

Collection of Biological Samples
Ten ml of blood was taken from all consenting students (817 female and 518 male). Blood samples were centrifuged at 1,500 x g for 10 min and aliquoted into plasma, buffy coats, and RBC. A majority of students consenting to blood collection also consented to provide samples of exfoliated genital cells (648 female and 366 male; ref. 3). Female students underwent self-collection of cervicovaginal cells, which has shown to be an appropriate alternative to physician-collected samples (26). Male students underwent collection of exfoliated genital cells from the scrotum, shaft, coronal sulcus, glans, urethral opening, and tip of the penis, done by an urologist (all placed into one tube and described in detail previously; ref. 3). Exfoliated genital cell samples from both female and male students were placed in PBS. Aliquots of blood and exfoliated genital cells were stored at –70°C.

HPV Serology Testing
Antibodies to the major capsid protein L1 of HPV types 16, 18, 31, 33, 45, 52, and 58 were tested for at the German Cancer Research Center, Heidelberg, Germany, using a multiplex HPV serology method based on a glutathione S-transferase (GST) capture immunosorbent assay (25). Viral antigens were expressed in Escherichia coli as double-fusion proteins with a NH₂-terminal GST domain and a COOH-terminal peptide derived from the large T antigen of SV40. Glutathione-casein was coupled to internally fluorescence-labeled polystyrene beads (Luminex), and antigen fusion proteins were affinity purified on the beads directly in a one-step procedure. Beads coupled with GST only were prepared for background determination. Binding of the antigens (i.e., GST fusion proteins) to various beads was verified with a monoclonal antibody against the common COOH-terminal peptide. The differently labeled beads carrying different antigens were then mixed and incubated in 96-well plates with human serum that had been diluted 1:100 in blocking buffer. Antibodies bound to the beads via the viral antigens were then stained with biotinylated anti-human immunoglobulin and the fluorescent reporter conjugate streptavidin-R-phycoerythrin (Molecular Probes). Antibodies bound to antigens on beads were quantified in the Luminex analyzer, which also identified the antigen by the internal bead color. Antibody quantity was determined as the median R-phycoerythrin fluorescence intensity (MFI) from at least 100 beads of the same internal color.

MFI values were dichotomized as antibody positive or negative. Seropositivity cutoffs were calculated independently for each HPV type by analyzing MFI values obtained for 371 female students from the present study that reported never to have engaged in penetrative sexual intercourse and had no evidence of genital HPV DNA for 25 HPV types (see below). The mean and SD of MFI values for these 371 subjects were calculated, and values greater than the mean + 5 SDs were excluded as outliers. This process was repeated on the remaining samples until no additional values could be excluded by this criterion, which occurred after one to four rounds of exclusion, depending on the HPV type. The final numbers of excluded outliers were 7, 13, 11, 1, 12, 4, and 3 for HPV types 16, 18, 31, 33, 45, 52, and 58, respectively. The cutoff was defined as 5 SDs above the mean of the final distribution and ranged from 394 to 714 MFI, depending on the HPV type. Alternative classifications of seropositivity using 3 or 4 SDs, with or without exclusion of outliers, or defining a 95% to 99% specificity threshold among virgins, yielded similar conclusions. For the following analyses, seropositivity for any HPV refers to that for types 16, 18, 31, 33, 45, 52, or 58, and multiple seropositivity as being positive for two or more of these types.

HPV DNA Testing
HPV DNA testing was done at DDL Diagnostic Laboratory (Voorburg, the Netherlands) as previously described (3). In brief, DNA was isolated from exfoliated genital cell samples, and HPV DNA was amplified by use of the short PCR fragment (SPF)₁₀ primer set (27). Amplification products were first tested by probe hybridization in a microtiter-plate assay to detect the presence of HPV DNA. SPF₁₀ amplimers from HPV DNA-positive samples were subsequently analyzed by reverse hybridization in an HPV line-probe assay (LiPA; ref. 28), permitting detection of 25 HPV types: HPV6, 11, 16, 18, 31, 33 to 35, 39, 40, 42 to 45, 51 to 54, 56, 58, 59, 66, 68/73, 70, and 74. Samples negative for a positive DNA control, the ß-globin gene, were considered invalid (6 women and 72 men). DNA positivity is reported in the manuscript as that for (a) all 25 types or (b) only the seven types for which serology data were also available.

Statistical Analysis
Gender-specific odds ratios (OR) for HPV seropositivity and corresponding 95% confidence intervals (95% CI) were calculated by means of logistic regression, with adjustment for lifetime number of sexual partners where appropriate (Stata version 9). The statistical significance of trends was assessed by considering categorical variables as a continuous variable in the logistic model.

	Results

Top Abstract Introduction Subjects, Materials, and Methods Results Discussion References

 
A total of 817 female and 518 male students with valid HPV serology results were included in the following analyses. Of these, a subset of 648 women and 366 men also had valid results for genital HPV DNA. Self-reported information on sexual activity was available for a subset of 680 women and 466 men, of which 502 (74%) and 206 (44%), respectively, reported never having engaged in penetrative sexual intercourse.

Overall and type-specific HPV seroprevalence is shown in Fig. 1 , stratified by gender and sexual activity status. Overall HPV seroprevalence did not differ significantly between female and male students (15% and 12%, respectively), which was also the case for type-specific HPV seroprevalence.

View larger version (18K): [in this window] [in a new window] [Download PPT slide]   Figure 1. HPV type-specific seroprevalence among 680 female and 466 male university students by gender (A) and sexual activity status (B and C). (Data not shown for 137 female and 52 male students of unknown sexual activity status in parts B and C. *, P < 0.05 for comparison of not sexually active and sexually active.).

Type-specific HPV seroprevalence is shown in Table 1 stratified by genital HPV DNA status (25 HPV types) and gender. Among women, there was a significant trend of increasing HPV seroprevalence from HPV DNA-negative women (12.9% for any HPV type), through women DNA positive for HPV types other than 16, 18, 31, 33, 45, 52, and 58 (17.4%), to that among women DNA positive for 16, 18, 31, 33, 45, 52, or 58 (40.7%). Furthermore, among HPV DNA-positive women, type-specific seroprevalence was always higher among women positive for the same HPV type (with the exception of HPV33 and 45 where the comparison was limited by only one and two HPV DNA-positive cases, respectively). For men, type-specific seroprevalence is only shown for HPV16 and 18 and the combination of 16, 18, 31, 33, 45, 52, and 58, on account of the low level of HPV DNA and seropositivity (Table 1). No positive correlation between HPV seropositivity and genital HPV DNA status was observed for any HPV type nor for HPV16 or 18 alone among men.

	Discussion

Top Abstract Introduction Subjects, Materials, and Methods Results Discussion References

 
Type-specific HPV seroprevalence was estimated in a young student population in South Korea, including many unmarried and/or virgin women that are normally unwilling to undergo gynecological examination and a comparative sample of men, with extensive validation against HPV DNA in genital samples.

Of 500 female Korean students reporting no history of penetrative sexual intercourse, seroprevalence to HPV16, 18, 31, 33, 45, 52, or 58 was 13% (Figure 1), whereas prevalence of genital HPV DNA for these seven types was only 1%. Other studies have reported HPV seroprevalence of 2% to 3% (HPV16 only) in young women who were virgins (6, 29), and others report 2% to 8% in children with a significant linear increase by age for girls (2, 30). It remains that sexual activity was a self-reported measure in the present study and may have been under-reported, particularly among women. Nevertheless, taken together, these data suggest that exposure and seroconversion to oncogenic HPV types may occur, to a certain extent, before penetrative sexual intercourse (10).

HPV seroprevalence doubled to 25% among sexually active women in this study, and this increase was seen independently for each of the seven HPV types tested. Although a strong increase in HPV seropositivity with increasing number of sexual partners has been widely reported (5-16), far fewer studies have allowed a comparison with women reporting to be nonsexually active (6, 29).

Nevertheless, the association of the lifetime number of sexual partners remained much weaker for HPV seroprevalence than for genital HPV DNA prevalence. This association was strongest for women that were both HPV seropositive and DNA positive, but these subjects were few (2%) among the pool of women positive for either marker (17%).

HPV DNA-positive women were more likely to be seropositive for antibodies to the same HPV type, confirming the type-specific nature of the immune response and the serologic assay. Nevertheless, the overall individual concordance between anti-HPV seropositivity and DNA positivity remained modest. At least three quarters of women infected with a given HPV type were not seropositive for the same HPV genotype. This proportion of non-seroconversion is higher than among older women from the same Korean population (31) and in some other studies (13, 14, 32), perhaps reflecting the effect of a time lag required for seroconversion in this young population. The 12-month cumulative incidence of seroconversion after cervical HPV infection has been estimated at 50% (1, 7, 22), and the majority of the sexually active women in this study had initiated sexual activity only within the preceding 12 months.

In contrast to their female peers, becoming sexually active and having multiple lifetime sexual partners had no observable effect on HPV seroprevalence or, as already shown, on genital HPV DNA prevalence among young men (3), despite higher self-reported levels of sexual activity than women. Higher seroprevalence among sexually active women than sexually active men has previously been reported from various populations for HPV (6, 10-12) and also for herpes simplex virus type 2 (10, 33). This discrepancy may reflect greater transience of HPV infection in male external genitalia than in the female vagina and cervix, as persistent exposure to the virus over time seems to be required for seroconversion in women (1). On the other hand, some previous studies have observed an association of HPV seroprevalence with the number of sexual partners, albeit among men of a much broader age range (11, 12). This apparent discrepancy could reflect an importance of duration of exposure in determining seroconversion or differences in HPV infection status of sexual partners, for example, if young men have sex with young women of low HPV prevalence.

This seroepidemiologic study is the first to correlate seroprevalence in men with genital HPV DNA for a wide range of types and shows that the correlation between these two markers is very poor, as shown previously for HPV16 (12, 34). This may partly reflect the difficulty to accurately classify HPV DNA status in males in whom a broader area of external genitalia need to be sampled in comparison to women.

HPV16 accounts for more than half of cervical cancers in Korea and worldwide (35). Likewise, HPV16 DNA predominates over that of other oncogenic HPV types in cancer-free women in South Korea (31). However, this predominance does not seem to be reflected in seroprevalence, for which HPV16, 18, and 31 are equivalent, as reported previously in Korea (31) and elsewhere (14, 36). The reason for the difference in type distribution at the serologic and DNA levels is unclear, but may be related to type-specific differences in duration of infection or propensity to elicit a serologic response. Cross-reactivity of serotypes cannot be ruled out, but only one quarter of all HPV-seropositive cases had multiple seropositivity, and there were too few to allow a statistical comparison of concordance between different serotypes. Using a less or more stringent cutoff for seropositivity while having the effect to increase or decrease, respectively, overall HPV seropositivity did not alter this type-specific equivalence or any other key differences by gender.

After accounting for confounding by number of sexual partners, we could not show associations of seropositivity in women with age or age at first penetrative sexual intercourse as in previous studies (14, 31), but the range in these variables was small in this student population. Oral contraceptive use was too rare to be evaluated as a determinant of seropositivity.

In summary, although seroprevalence may underestimate cumulative exposure to HPV due to low seroconversion rates, it seems to be a useful molecular epidemiologic tool to assess HPV infection in young women unwilling to undergo gynecological examination, with potential application in monitoring the effect of HPV vaccines. The utility of seroprevalence has been increased further with the development of cost-efficient high-throughput assays, of the type used in this study, that allow the simultaneous analysis of antibodies against a large number of HPV types (25, 37). As is the case for HPV DNA prevalence, the significance of HPV seroprevalence among young men remains unclear.

	Footnotes

 
Grant support: Bill & Melinda Gates Foundation (Grant no. 35537) and the Korean National Cancer Centre (Grant no. 0110250).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 4/17/07; revised 6/13/07; accepted 6/21/07.

	References

Top Abstract Introduction Subjects, Materials, and Methods Results Discussion References

 

1. Ho GY, Studentsov YY, Bierman R, Burk RD. Natural history of human papillomavirus type 16 virus-like particle antibodies in young women. Cancer Epidemiol Biomarkers Prev 2004;13:110–6.[Abstract/Free Full Text]
2. Dunne EF, Nielson CM, Stone KM, Markowitz LE, Giuliano AR. Prevalence of HPV infection among men: a systematic review of the literature. J Infect Dis 2006;194:1044–57.[CrossRef][Medline]
3. Shin HR, Franceschi S, Vaccarella S, et al. Prevalence and determinants of genital infection with papillomavirus, in female and male university students in Busan, South Korea. J Infect Dis 2004;190:468–76.[CrossRef][Medline]
4. Sukvirach S, Smith JS, Tunsakul S, et al. Population-based human papillomavirus prevalence in Lampang and Songkla, Thailand. J Infect Dis 2003;187:1246–56.[CrossRef][Medline]
5. Castle PE, Wacholder S, Lorincz AT, et al. A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women. J Natl Cancer Inst 2002;94:1406–14.[Abstract/Free Full Text]
6. Stone KM, Karem KL, Sternberg MR, et al. Seroprevalence of human papillomavirus type 16 infection in the United States. J Infect Dis 2002;186:1396–402.[CrossRef][Medline]
7. Carter JJ, Koutsky LA, Wipf GC, et al. The natural history of human papillomavirus type 16 capsid antibodies among a cohort of university women. J Infect Dis 1996;174:927–36.[Medline]
8. Dillner J, Kallings I, Brihmer C, et al. Seropositivities to human papillomavirus types 16, 18, or 33 capsids and to Chlamydia trachomatis are markers of sexual behavior. J Infect Dis 1996;173:1394–8.[Medline]
9. Hagensee ME, Slavinsky J III, Gaffga CM, Suros J, Kissinger P, Martin DH. Seroprevalence of human papillomavirus type 16 in pregnant women. Obstet Gynecol 1999;94:653–8.[CrossRef][Medline]
10. Kreimer AR, Alberg AJ, Viscidi R, Gillison ML. Gender differences in sexual biomarkers and behaviors associated with human papillomavirus-16, -18, and -33 seroprevalence. Sex Transm Dis 2004;31:247–56.[Medline]
11. Strickler HD, Kirk GD, Figueroa JP, et al. HPV 16 antibody prevalence in Jamaica and the United States reflects differences in cervical cancer rates. Int J Cancer 1999;80:339–44.[CrossRef][Medline]
12. Svare EI, Kjaer SK, Nonnenmacher B, et al. Seroreactivity to human papillomavirus type 16 virus-like particles is lower in high-risk men than in high-risk women. J Infect Dis 1997;176:876–83.[Medline]
13. Viscidi RP, Kotloff KL, Clayman B, Russ K, Shapiro S, Shah KV. Prevalence of antibodies to human papillomavirus (HPV) type 16 virus-like particles in relation to cervical HPV infection among college women. Clin Diagn Lab Immunol 1997;4:122–6.[Medline]
14. Wang SS, Schiffman M, Shields TS, et al. Seroprevalence of human papillomavirus-16, -18, -31, and -45 in a population-based cohort of 10,000 women in Costa Rica. Br J Cancer 2003;89:1248–54.[CrossRef][Medline]
15. Wideroff L, Schiffman MH, Hoover R, et al. Epidemiologic determinants of seroreactivity to human papillomavirus (HPV) type 16 virus-like particles in cervical HPV-16 DNA-positive and-negative women. J Infect Dis 1996;174:937–43.[Medline]
16. Wang ZH, Kjellberg L, Abdalla H, et al. Type specificity and significance of different isotypes of serum antibodies to human papillomavirus capsids. J Infect Dis 2000;181:456–62.[CrossRef][Medline]
17. Nonnenmacher B, Hubbert NL, Kirnbauer R, et al. Serologic response to human papillomavirus type 16 (HPV-16) virus-like particles in HPV-16 DNA-positive invasive cervical cancer and cervical intraepithelial neoplasia grade III patients and controls from Colombia and Spain. J Infect Dis 1995;172:19–24.[Medline]
18. Chua KL, Wiklund F, Lenner P, et al. A prospective study on the risk of cervical intra-epithelial neoplasia among healthy subjects with serum antibodies to HPV compared with HPV DNA in cervical smears. Int J Cancer 1996;68:54–9.[CrossRef][Medline]
19. Strickler HD, Dillner J, Schiffman MH, et al. A seroepidemiologic study of HPV infection and incident cervical squamous intraepithelial lesions. Viral Immunol 1994;7:169–77.[Medline]
20. Dillner J, Lehtinen M, Bjorge T, et al. Prospective seroepidemiologic study of human papillomavirus infection as a risk factor for invasive cervical cancer. J Natl Cancer Inst 1997;89:1293–9.[Abstract/Free Full Text]
21. Sigstad E, Lie AK, Luostarinen T, et al. A prospective study of the relationship between prediagnostic human papillomavirus seropositivity and HPV DNA in subsequent cervical carcinomas. Br J Cancer 2002;87:175–80.[Medline]
22. Carter JJ, Koutsky LA, Hughes JP, et al. Comparison of human papillomavirus types 16, 18, and 6 capsid antibody responses following incident infection. J Infect Dis 2000;181:1911–9.[CrossRef][Medline]
23. Kirnbauer R, Hubbert NL, Wheeler CM, Becker TM, Lowy DR, Schiller JT. A virus-like particle enzyme-linked immunosorbent assay detects serum antibodies in a majority of women infected with human papillomavirus type 16. J Natl Cancer Inst 1994;86:494–9.[Abstract/Free Full Text]
24. Thompson DL, Douglas JM, Jr., Foster M, et al. Seroepidemiology of infection with human papillomavirus 16, in men and women attending sexually transmitted disease clinics in the United States. J Infect Dis 2004;190:1563–74.[CrossRef][Medline]
25. Waterboer T, Sehr P, Michael KM, et al. Multiplex human papillomavirus serology based on in situ-purified glutathione S-transferase fusion proteins. Clin Chem 2005;51:1845–53.[Abstract/Free Full Text]
26. Ogilvie GS, Patrick DM, Schulzer M. Diagnostic accuracy of self collected vaginal specimens for human papillomavirus compared with clinician collected human papillomavirus specimens: a meta-analysis. Sex Transm Infect 2005;81:207–12.[Abstract/Free Full Text]
27. Kleter B, van Doorn LJ, ter Schegget J, et al. Novel short-fragment PCR assay for highly sensitive broad-spectrum detection of anogenital human papillomaviruses. Am J Pathol 1998;153:1731–9.[Abstract/Free Full Text]
28. Kleter B, van Doorn LJ, Schrauwen L, et al. Development and clinical evaluation of a highly sensitive PCR-reverse hybridization line probe assay for detection and identification of anogenital human papillomavirus. J Clin Microbiol 1999;37:2508–17.[Abstract/Free Full Text]
29. Studentsov YY, Ho GY, Marks MA, Bierman R, Burk RD. Polymer-based enzyme-linked immunosorbent assay using human papillomavirus type 16 (HPV16) virus-like particles detects HPV16 clade-specific serologic responses. J Clin Microbiol 2003;41:2827–34.[Abstract/Free Full Text]
30. Dunne EF, Burstein GR, Stone KM. Anogenital human papillomavirus infection in males. Adolesc Med 2003;14:613–32.[Medline]
31. Shin HR, Lee DH, Herrero R, et al. Prevalence of human papillomavirus infection in women in Busan, South Korea. Int J Cancer 2003;103:413–21.[CrossRef][Medline]
32. Andersson-Ellstrom A, Dillner J, Hagmar B, et al. Comparison of development of serum antibodies to HPV16 and HPV33 and acquisition of cervical HPV DNA among sexually experienced and virginal young girls. A longitudinal cohort study. Sex Transm Dis 1996;23:234–8.[Medline]
33. Fleming DT, McQuillan GM, Johnson RE, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med 1997;337:1105–11.[Abstract/Free Full Text]
34. Hagensee ME, Kiviat N, Critchlow CW, et al. Seroprevalence of human papillomavirus types 6 and 16 capsid antibodies in homosexual men. J Infect Dis 1997;176:625–31.[Medline]
35. Smith JS, Lindsay L, Keys J, et al. HPV type distribution in invasive cervical cancer and high-grade cervical neoplasia: an update of meta-analyses and identification of global data gaps. Int J Cancer 2007;121:621–32.[CrossRef][Medline]
36. Marais DJ, Rose RC, Lane C, et al. Seroresponses to human papillomavirus types 16, 18, 31, 33, and 45 virus-like particles in South African women with cervical cancer and cervical intraepithelial neoplasia. J Med Virol 2000;60:403–10.[CrossRef][Medline]
37. Dias D, Van Doren J, Schlottmann S, et al. Optimization and validation of a multiplexed luminex assay to quantify antibodies to neutralizing epitopes on human papillomaviruses 6, 11, 16, and 18. Clin Diagn Lab Immunol 2005;12:959–69.[CrossRef][Medline]

This article has been cited by other articles:

				S. Syrjanen, T. Waterboer, M. Sarkola, K. Michael, M. Rintala, K. Syrjanen, S. Grenman, and M. Pawlita Dynamics of human papillomavirus serology in women followed up for 36 months after pregnancy J. Gen. Virol., June 1, 2009; 90(6): 1515 - 1526. [Abstract] [Full Text] [PDF]

				N. P. Dickson, J. Ryding, T. van Roode, C. Paul, P. Herbison, J. Dillner, and D. C.G. Skegg Male Circumcision and Serologically Determined Human Papillomavirus Infection in a Birth Cohort Cancer Epidemiol. Biomarkers Prev., January 1, 2009; 18(1): 177 - 183. [Abstract] [Full Text] [PDF]

				B. Dondog, G. M. Clifford, S. Vaccarella, T. Waterboer, D. Unurjargal, D. Avirmed, S. Enkhtuya, F. Kommoss, N. Wentzensen, P. J.F. Snijders, et al. Human Papillomavirus Infection in Ulaanbaatar, Mongolia: A Population-Based Study Cancer Epidemiol. Biomarkers Prev., July 1, 2008; 17(7): 1731 - 1738. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Clifford, G. M. Articles by Franceschi, S. Search for Related Content PubMed PubMed Citation Articles by Clifford, G. M. Articles by Franceschi, S.