Cancer Epidemiology Biomarkers & Prevention Vol. 9, 953-959, September 2000
© 2000 American Association for Cancer Research
Correlates of the Spread of Human Papillomavirus Infection1
Ilvars Silins,
Ingegerd Kallings and
Joakim Dillner2
Laboratory of Tumor Virus Epidemiology, Microbiology and Tumor Biology Center, Karolinska Institute, S-17177 Stockholm, Sweden [I. S., J. D.]; Swedish Institute for Infectious Disease Control, S-17182 Stockholm, Sweden [I. K., J. D.]; and Department of Infectious Disease Epidemiology, National Public Health Institute, FIN-00300 Helsinki, Finland [J. D.]
 |
Abstract
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Knowledge of the correlates of human papillomavirus (HPV) seropositivity
is of interest for planning of preventive measures and for evaluation
of possible confounding in epidemiological studies. The epidemiological
determinants for seropositivity for oncogenic and benign HPV types were
assessed using a serosurvey of 275 healthy Swedish women, stratified by
age and lifetime number of sexual partners. Seroprevalences were
compared with 17 behavioral variables obtained by interview and 3
laboratory-diagnosed microbiological exposures. In univariate analysis,
history of gonorrhea and condylomatosis, human herpesvirus type 8 and
herpes simplex virus 2 seropositivities, lifetime number of sexual
partners, and current partner’s lifetime number of sexual partners
were associated with oncogenic HPV seropositivity. Noteworthy lack of
correlations included smoking habits and oral contraceptive use. In
multivariate analysis, only the number of lifetime sexual partners
[odds ratio (OR), 8.7; 95% confidence interval (CI), 3.3–22.6] and
seropositivity for benign HPV types remained significant (OR, 2.9; 95%
CI, 1.6–5.3). Seropositivity for benign HPV was primarily associated
with condyloma history (OR, 3.6; 95% CI, 1.2–10.8) and seropositivity
for oncogenic HPV (OR, 2.9; 95% CI, 1.6–5.2). An association with
sexual history lost significance in the multivariate model. In
conclusion, lifetime number of sexual partners is the major determinant
of acquisition of oncogenic HPV. By contrast, benign HPV infection
associates more strongly with condyloma history than with sexual
history per se.
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Introduction
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Oncogenic
HPVs3
are established as the main epidemiological risk factor for cervical
cancer (1)
and are also implicated as risk factor for
penile, vulvar, vaginal, anal, and oropharyngeal cancers (2
, 3)
. Knowledge of behavioral and other determinants of HPV
acquisition is important to be able to plan preventive measures. Also,
knowledge of whether HPV exposure is correlated to other risk factors
for cancer can provide information regarding possible confounding in
epidemiological studies of HPV and cancer. Several studies have found
that determinants of acquisition of benign HPV types (HPV 6 and 11)
differ from those of the oncogenic HPV types (4
, 5)
, the
most notable difference being a weaker (or even absent) association
with sexual history. This finding is relevant for the issue of whether
prevention of oncogenic HPV infection should target populations known
to be at risk of condylomatosis. Also, comparison of determinants of
acquisition of different HPV types is interesting because of recent
indications that infection with a benign HPV type may antagonize the
oncogenic effect of infection with a major oncogenic HPV type (6
, 7)
.
HPV infection is commonly assessed using detection of viral DNA in
cervical cells (8)
. However, HPV infection shows a dynamic
pattern with a very high rate of infection in the first years after the
sexual debut (9)
and a high rate of spontaneous clearance:
70% of infections are cleared after 1 year (9, 10, 11)
.
Therefore, studies of correlates of HPV infection based on HPV DNA
detection are inherently biased by the fact that they cannot
distinguish between correlates of HPV acquisition and correlates of HPV
clearance. A more useful way to study correlates of lifetime exposure
to HPV is to study serum antibody responses. Serum antibody responses
to HPV type 16 are stable over time (12
, 13)
and correlate
with the lifetime number of sexual partners (14
, 15)
.
The aim of our study was to determine the epidemiological correlates of
exposure to benign and oncogenic HPV types among healthy women in
Sweden, using serology as the measure of exposure.
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Materials and Methods
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The study participants were recruited at three family planning
clinics in the cities of Eskilstuna and Stockholm in Sweden (November
1989–January 1991). The studied women had attended these clinics for
contraceptive advice. One thousand seventy-seven women were invited to
participate. Sixty-six women (6.2%) refused enrolment, 9 did not
successfully complete the interview or the sampling, and 1002 were
eligible for evaluation. The mean age was 26 years (range, 16–48
years).
Lifetime number of sexual partners is an age-dependent variable, and it
is therefore possible that age could act as a confounder between
lifetime number of sexual partners and the behavioral and environmental
factors investigated in this study. To save cost while focusing on a
subset of women in whom the association between age and lifetime number
of sexual partners was eliminated in the study design, the 1002
subjects were stratified in 30 cells: five strata were according to the
number of lifetime sexual partners (1; 2 or 3; 4 or 5; 6–10; and >10
partners) and six strata were according to the age in 5-year intervals
(<20; 20–24; 25–29; 30–34; 35–39; and >39 years of age). Then a
stratified subsample of 275 women was obtained by unweighted random
number-determined selection of a cell and of a sample within a cell.
This procedure resulted in five sexual behavior strata that were very
similar in their age distribution, as described previously in detail
(16)
. To investigate whether the effect of age had indeed
been eliminated, the associations of the major investigated exposures
with the lifetime number of sexual partners were also tested with
adjustment for age in quartiles and quintiles. The results were
virtually identical (data not shown).
Questionnaire.
Trained personnel conducted personal interviews with the study
participants. The questionnaire included questions on social habits,
e.g., smoking, use of alcohol and different drugs, and detailed sexual
information on, e.g., first intercourse, number of recent
and lifetime sexual partners, STDs, and experiences of oral, anal, and
group sex. Confidentiality was guaranteed for all of the study
participants to ensure as frank and complete answers as possible.
Laboratory Methods.
Serum IgG antibodies to HPV 6, 11, 16, 18, and 33 capsids were measured
by the standard two-step ELISA methods using a monoclonal antibody
against human IgG and a goat antimouse IgG horseradish peroxidase
conjugate (17)
. For each serum, the difference in
absorbance obtained with plates coated with intact HPV capsids and
plates coated with control antigen (disrupted bovine papilloma
virus capsids) was calculated. The exact methodology is the same
as described previously (14)
. The cutoff points for
determining seropositivity were, relative to internal standard sera,
also the same as used previously (14)
. The assays were
done in duplicate, samples with discrepant results were analyzed two
more times, and the consensus results from the last tests were used.
The assay used in our laboratory has been validated as highly specific
for the sexually transmitted HPV types, because monogamous or virginal
women show very low prevalences (16)
. The sensitivity is
moderate, however, and has (using HPV DNA detection as gold standard)
been estimated at 50–65% (18)
. The actual serological
laboratory analyses for HPV 11, 16, 18, and 33 but not for HPV 6 are
the same as in our previous study (14)
. However, none of
the statistical analyses are published previously.
Statistical Analysis.
Statistica software was used for data analysis. ORs and CIs were
calculated using logistic regression.
Multivariate analysis was performed by initially including all of the
determinants in the model. Thereafter, determinants with no significant
relation and no biological rationale for inclusion in the model were
excluded. To enable comparison, the final multivariate analysis models
were identical for both oncogenic and benign HPV types and included the
three determinants that had been significant in either of the initial
models and three determinants (smoking, condom use, and
Chlamydia antibodies) that were considered relevant because
of previously known experimental and/or epidemiological associations.
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Results
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Sexual History.
As in previous studies, HPV types 16,18,33 seropositivity strongly
correlated with the lifetime number of sexual partners but reached a
plateau at 6–10 lifetime partners with an overall seroprevalence for
HPV types 16,18,33 of 53%. The HPV 6,11 seroprevalence had a similar
but less pronounced trend, reaching a 42% seroprevalence for women
having more than five lifetime sexual partners (Fig. 1)
.
To explore possible explanations for HPV negativity among the
high-risk women, the epidemiological profile of the women on the
"plateau" (i.e., with more than five partners) according
to their HPV serostatus was investigated. There were, however, few
differences. Complete absence of condyloma history among jointly
HPV-seronegative women was the only significant difference
(P < 0.001).
Although the seroprevalence curve for HPV 16,18,33 appeared to
intercept the Y-axis at the origo, the HPV 6,11
seroprevalence curve started from a 12% seroprevalence (polynomial
regression; 95% CI at the Y-axis intercept: 0.0–23%),
suggesting that there might exist either a nonsexual transmission or a
substantial nonspecific component of the HPV 6,11 serology.
ORs for seropositivity to oncogenic types was >10 for those with >6
lifetime partners, when women with 1 lifetime sexual partner were used
as the reference group (Table 1)
. For the benign HPV types the corresponding OR was >4 (Table 2)
. By contrast, no correlation was found with the number of recent
sexual partners (in last 6 months), neither for oncogenic, nor for
benign HPV types (Tables 1
2)
. HPV seropositivity was strongly
associated with the number of lifetime sexual partners of the current
partner of the woman (Tables 1
2)
and the correlation was again
stronger for oncogenic HPV types. However, the association with
partner’s number of partners disappeared after adjustment for the
women’s lifetime number of partners (Tables 1
2)
.
Infection with Benign HPV Types.
The strongest correlation with HPV 6,11 seropositivity was found for
self-reported history of condylomas (OR, 6.2; 95% CI, 2.3–16.9; Table 2
). Seropositivity to the benign papillomavirus types was also
dependent on HPV 16,18,33 seropositivity (OR, 3.6; 95% CI, 2.1–6.2).
In univariate analysis, seropositivity for benign HPV types was also
associated with gonorrhea history (OR, 3.5; 95% CI, 1.3–9.0) and
long-term smoking (OR, 2.0; 95% CI, 1.2–3.7; Table 2
). Age tended to
associate with seropositivity, mostly because of a low seroprevalence
among the youngest women (Tables 1
2)
. In multivariate
analysis, HPV 6,11 correlated only with seropositivity for oncogenic
HPV types and with condyloma history (Table 3)
.
Exclusion of condyloma history from the multivariate model (to avoid
adjusting for factors on the same causal pathways) had little effect on
the correlation with sexual behavior (OR, 1.7; 95% CI, 0.7–4.6
versus OR, 2.0; 95% CI, 0.8–5.3).
Infection with Oncogenic HPV Types.
Frequent alcohol use (P = 0.07), in particular beer
drinking (P = 0.006), was associated with
seropositivity for oncogenic HPV types. Seropositivity was also more
common among women with a history of various STDs: gonorrhea
(P = 0.007), condyloma (P = 0.003),
human herpesvirus 8 seropositivity (P = 0.04), and
herpes simplex virus type 2 seropositivity (P = 0.02).
Chlamydia trachomatis seropositivity detected by the
immunofluorescence method showed a marginally significant association
with oncogenic HPV (P = 0.06). Risk for seropositivity
for the oncogenic HPV types was higher among women seropositive for
benign HPV types (Table 1)
.
Smokers and nonsmokers had similar HPV seroprevalences, albeit
long-term smokers (>5 years) tended to be more commonly positive for
oncogenic HPV infection (Table 1)
. Regular condom users had a tendency
to be less frequently HPV positive (P = 0.06).
After adjustment for the number of lifetime sexual partners, gonorrhea
and condyloma history lost correlation with oncogenic HPV
seropositivity, and Chlamydia history even tended to be
weakly negatively associated with HPV seropositivity (Table 1)
.
Similarly, after adjustment for lifetime number of partners, neither
alcohol use nor OC use were associated with oncogenic HPV. Adjustment
for partner number also revealed a negative association between
oncogenic HPV and smoking (Table 1)
, and condom usage was not any more
associated with lower HPV seroprevalences after adjustment, in line
with the strong trend for lower usage among women with more partners
(Fig. 2)
. Also for oncogenic HPV types, exclusion of condyloma had little
effect on the sexual behavior estimate (OR, 8.0; 95% CI, 3.1–21.1
versus OR, 8.7; 95% CI, 3.3–22.6).
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Fig. 2. Regular condom use and lifetime number of sexual partners. Proportion
of women reporting always or almost always use of condoms during sexual
intercourse in relation to their lifetime number of sexual partners.
The P for trend was calculated using ANOVA and was
<0.001.
|
|
Multivariate analysis revealed the number of lifetime sexual partners
and HPV 6,11 seropositivity as the only statistically significant
correlates of seroprevalence for oncogenic HPV (Table 4)
.
|
Discussion
|
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The association of oncogenic HPV infection with the lifetime
number of sexual partners is already well known (14
, 19)
.
In univariate analysis, history of several STDs and a current male
partner with a high number of lifetime sexual partners also showed a
correlation with oncogenic HPV infection. The association with
partner’s number of partners was explained by a strong trend for women
with a high number of partners to have partners with a high number of
partners. This phenomenon (contact preferences/nonrandom mixing) is
well known in venereology (20)
. In multivariate
analysis, the number of lifetime sexual partners of the woman was the
only important determinant. Seropositivity for either the oncogenic or
benign HPV types also conferred an increased risk to be seropositive
for the other HPV group. This risk was significant for both HPV groups
also in multivariate analysis. Among HPV 16,18,33 seropositives, the
proportion of seropositives for the benign HPV types does not depend on
the number of lifetime sexual partners, being approximately equal for
each partner category (40–53% being also positive for benign types).
Among the women seronegative for the oncogenic HPV types, the
proportion of HPV 6,11 seropositives is smaller and reached only
28–31%, even for women with more than six partners. Apparently, a
woman who has seroconverted for one HPV type has a higher probability
to seroconvert also for other HPV types. There could be several
explanations for this phenomenon: (a)
cross-reactivity/imperfect type-specificity of the HPV serology is well
known to occur between HPV 6 and 11 (21)
but does not
occur to any significant extent between the other HPV types and could
thus only partially explain the phenomenon; (b) there might
exist sociological determinants of HPV acquisition that are the same
for the different HPV types but that could not be defined by the
questionnaires; and (c) there might exist a "responder"
and "nonresponder" phenotype among women, e.g., if the
antibody response is under control of immune-response genes.
Although smoking habits commonly correlate with presence of cervical
lesions or cancer (22
, 23)
, we found no association of
smoking with the prevalence of HPV in crude analyses, and after
adjustment for lifetime sexual partners, oncogenic HPV seropositivity
has even a trend for negative association with smoking (OR
0.6). Several previous studies have reported a tendency for decreased
risk of persistence of HPV infection among smokers (4
, 9
, 24)
.
The lack of association with smoking is noteworthy, because smoking and
HPV acquisition have been strongly correlated in studies from several
parts of the world. Possibly, smoking habits may be common also outside
of HPV acquisition risk groups because of the high proportion of
smokers among the Swedish women in this study ( 40%).
Several studies have described an increased risk for HPV infection with
OC use (19
, 25
, 26)
. In our study, OC usage had no
correlation with HPV seropositivity, neither in crude analysis nor when
adjusted for number of lifetime sexual partners. However, OC use was
associated with current sexual activity and with a high number of
sexual partners in the previous 6 months (66% and 86% for 0–1 and
>1 partner, respectively; P = 0.005), in line with
presently sexually active women being more interested in OC use.
Residual confounding by recent sexual history could be a possible
explanation for increased HPV prevalence among OC users in other
studies, particularly if young populations are studied or the measure
of infection is HPV DNA, which is known to correlate primarily with
recent sexual history. Another explanation that has been proposed is
that only use of high-dose OCs but not use of low dose OCs correlates
with HPV detectability (26)
. A suggested mechanism that
could mediate a correlation is that hormone receptors in the cervix may
influence the viral load (19)
.
Our study supports the sexually transmitted nature of HPV infection but
also discloses differences between benign and oncogenic virus types in
their transmission patterns. Lifetime number of sexual partners is,
e.g., not as strongly associated with risk for benign HPV
infection. This is in line with other studies that also have described
different properties of the infection with benign HPV types: shorter
duration of infection (5)
and lower correlation with
sexual activity (4
, 27)
.
|
Acknowledgments
|
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We thank Dr. Rosa Maria Tedeschi for the human
herpesvirus 8 analyses, Dr. Ulla Ruden for the herpes simplex
virus 2 analyses, Dr. Pentti Koskela for the
Chlamydia analyses, and Dr. John T. Schiller for the
papillomavirus capsids. We also thank Carina Eklund for technical
assistance and Drs. Matti Lehtinen, Per Anders Mårdh, Bo Frankendal,
and Elisabeth Åvall-Lundqvist for helpful discussions and support.
|
Footnotes
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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.
1 This work was supported by the Swedish Cancer
Society. I. S. is supported by the Karolinska Institute Research and
Training program, and J. D. is supported by the Swedish Medical
Research Council and by the Academy of Finland. 
2 To whom requests for reprints should be
addressed, at Microbiology and Tumor Biology Center, Box 280, S-17177
Stockholm, Sweden. E-mail: joakim.dillner{at}mtc.ki.se
3 The abbreviations used are: HPV, human
papillomavirus; OR, odds ratio; CI, confidence interval; STD, sexually
transmitted disease; OC, oral contraceptive.
Received 12/ 2/99;
revised 6/21/00;
accepted 7/ 6/00.
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References
|
|---|
-
Schiffman M. H., Bauer H. M., Hoover R. N., Glass A. G., Cadell D. M., Rush B. B., Scott D. R., Sherman M. E., Kurman R. J., Wacholder S. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J. Natl. Cancer Inst., 85: 958-964, 1993.[Abstract/Free Full Text]
-
Bjorge T., Dillner J., Anttila T., Engeland A., Hakulinen T., Jellum E., Lehtinen M., Luostarinen T., Paavonen J., Pukkala E., Sapp M., Schiller J., Youngman L., Thoresen S. Prospective seroepidemiological study of role of human papillomavirus in non-cervical anogenital cancers. Br. Med. J., 315: 646-649, 1997.[Abstract/Free Full Text]
-
Schwartz S. M., Daling J. R., Doody D. R., Wipf G. C., Carter J. J., Madeleine M. M., Mao E. J., Fitzgibbons E. D., Huang S., Beckmann A. M., McDougall J. K., Galloway D. A. Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection. J. Natl. Cancer Inst., 90: 1626-1636, 1998.[Abstract/Free Full Text]
-
Kjaer S. K., van den Brule A. J., Bock J. E., Poll P. A., Engholm G., Sherman M. E., Walboomers J. M., Meijer C. J. Determinants for genital human papillomavirus (HPV) infection in 1000 randomly chosen young Danish women with normal Pap smear: are there different risk profiles for oncogenic and nononcogenic HPV types?. Cancer Epidemiol. Biomark. Prev., 6: 799-805, 1997.[Abstract/Free Full Text]
-
Franco E. L., Villa L. L., Ruiz A., Costa M. C. Transmission of cervical human papillomavirus infection by sexual activity: differences between low and high oncogenic risk types. J. Infect. Dis., 172: 756-763, 1995.[Medline]
-
Silins I., Wang Z., Avall-Lundqvist E., Frankendal B., Vikmanis U., Sapp M., Schiller J. T., Dillner J. Serological evidence for protection by human papillomavirus (HPV) type 6 infection against HPV type 16 cervical carcinogenesis. J. Gen. Virol., 80: 2931-2936, 1999.[Abstract/Free Full Text]
-
Luostarinen, T., af Geijersstam, V., Bjorge, T., Eklund, C., Hakama, M., Hakulinen, T., Jellum, E., Koskela, P., Paavonen, J., Pukkala, E., Schiller, J. T., Thoresen, S., Youngman, L. D., Dillner, J., and Lehtinen, M. No excess risk of cervical carcinoma among women seropositive for both HPV16 and HPV6/11. Int. J. Cancer, 80: 818–722, 1999.
-
Rozendaal L., Walboomers J. M., van der Linden J. C., Voorhorst F. J., Kenemans P., Helmerhorst T. J., van Ballegooijen M., Meijer C. J. PCR-based high-risk HPV test in cervical cancer screening gives objective risk assessment of women with cytomorphologically normal cervical smears. Int. J. Cancer, 68: 766-769, 1996.[Medline]
-
Ho G. Y., Bierman R., Beardsley L., Chang C. J., Burk R. D. Natural history of cervicovaginal papillomavirus infection in young women. N. Engl. J. Med., 338: 423-428, 1998.[Abstract/Free Full Text]
-
Hildesheim A., Schiffman M. H., Gravitt P. E., Glass A. G., Greer C. E., Zhang T., Scott D. R., Rush B. B., Lawler P., Sherman M. E. Persistence of type-specific human papillomavirus infection among cytologically normal women. J. Infect. Dis., 169: 235-240, 1994.[Medline]
-
Evander M., Edlund K., Gustafsson A., Jonsson M., Karlsson R., Rylander E., Wadell G. Human papillomavirus infection is transient in young women: a population-based cohort study. J. Infect. Dis., 171: 1026-1030, 1995.[Medline]
-
af Geijersstam, V., Kibur, M., Wang, Z., Koskela, P., Pukkala, E., Schiller, J., Lehtinen, M., and Dillner, J. Stability over time of serum antibody levels to human papillomavirus type 16. J. Infect. Dis., 177: 1710–1714, 1998.
-
Carter J. J., Koutsky L. A., Wipf G. C., Christensen N. D., Lee S. K., Kuypers J., Kiviat N., Galloway D. A. The natural history of human papillomavirus type 16 capsid antibodies among a cohort of university women. J. Infect. Dis., 174: 927-936, 1996.[Medline]
-
Dillner J., Kallings I., Brihmer C., Sikstrom B., Koskela P., Lehtinen M., Schiller J. T., Sapp M., Mardh P. A. Seropositivities to human papillomavirus types 16, 18, or 33 capsids and to Chlamydia trachomatis are markers of sexual behavior. J. Infect. Dis., 173: 1394-1398, 1996.[Medline]
-
Olsen A. O., Dillner J., Gjoen K., Magnus P. Seropositivity against HPV 16 capsids: a better marker of past sexual behaviour than presence of HPV DNA. Genitourin. Med., 73: 131-135, 1997.[Medline]
-
Andersson-Ellstrom A., Dillner J., Hagmar B., Schiller J., Sapp M., Forssman L., Milsom I. 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., 23: 234-238, 1996.[Medline]
-
Heino P., Eklund C., Fredriksson-Shanazarian V., Goldman S., Schiller J. T., Dillner J. Association of serum immunoglobulin G antibodies against human papillomavirus type 16 capsids with anal epidermoid carcinoma. J. Natl. Cancer Inst., 87: 437-440, 1995.[Abstract/Free Full Text]
-
Kjellberg L., Wang Z., Wiklund F., Edlund K., Angstrom T., Lenner P., Sjoberg I., Hallmans G., Wallin K. L., Sapp M., Schiller J., Wadell G., Mahlck C. G., Dillner J. Sexual behaviour and papillomavirus exposure in cervical intraepithelial neoplasia: a population-based case-control study. J. Gen. Virol., 80: 391-398, 1999.[Abstract]
-
Wideroff L., Schiffman M. H., Hoover R., Tarone R. E., Nonnenmacher B., Hubbert N., Kirnbauer R., Greer C. E., Lorincz A. T., Manos M. M., Glass A. G., Scott D. R., Sherman M. E., Buckland J., Lowy D., Schiller J. 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., 174: 937-943, 1996.[Medline]
-
Garnett G. P., Hughes J. P., Anderson R. M., Stoner B. P., Aral S. O., Whittington W. L., Handsfield H. H., Holmes K. K. Sexual mixing patterns of patients attending sexually transmitted diseases clinics. Sex. Transm. Dis., 23: 248-257, 1996.[Medline]
-
Christensen N. D., Reed C. A., Cladel N. M., Hall K., Leiserowitz G. S. Monoclonal antibodies to HPV-6 L1 virus-like particles identify conformational and linear neutralising epitopes on HPV-11 in addition to type-specific epitopes on HPV-6. Virology, 224: 477-486, 1996.[Medline]
-
Ho G. Y., Kadish A. S., Burk R. D., Basu J., Palan P. R., Mikhail M., Romney S. L. HPV 16 and cigarette smoking as risk factors for high-grade cervical intra-epithelial neoplasia. Int. J. Cancer, 78: 281-285, 1998.[Medline]
-
Ngelangel C., Munoz N., Bosch F. X., Limson G. M., Festin M. R., Deacon J., Jacobs M. V., Santamaria M., Meijer C. J., Walboomers J. M. Causes of cervical cancer in the Philippines: a case-control study. J. Natl. Cancer Inst., 90: 43-49, 1998.[Abstract/Free Full Text]
-
Hildesheim A., Gravitt P., Schiffman M. H., Kurman R. J., Barnes W., Jones S., Tchabo J. G., Brinton L. A., Copeland C., Epp J. Determinants of genital human papillomavirus infection in low-income women in Washington, D. C. Sex. Transm. Dis., 20: 279-285, 1993.
-
Brisson J., Bairati I., Morin C., Fortier M., Bouchard C., Christen A., Bernard P., Roy M., Meisels A. Determinants of persistent detection of human papillomavirus DNA in the uterine cervix. J. Infect. Dis., 173: 794-799, 1996.[Medline]
-
Sikstrom B., Hellberg D., Nilsson S., Brihmer C., Mardh P. A. Contraceptive use and reproductive history in women with cervical human papillomavirus infection. Adv. Contracept., 11: 273-284, 1995.[Medline]
-
Franco E. L., Villa L. L., Sobrinho J. P., Prado J. M., Rousseau M. C., Desy M., Rohan T. E. Epidemiology of acquisition and clearance of cervical human papillomavirus infection in women from a high-risk area for cervical cancer. J. Infect. Dis., 180: 1415-1423, 1999.[Medline]
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The causal relation between human papillomavirus and cervical cancer
J. Clin. Pathol.,
April 1, 2002;
55(4):
244 - 265.
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Abstract
Introduction
) and oncogenic
(HPV 16,18,33; 
) HPV seropositives are plotted
in relation to the number of lifetime sexual partners. The
P values were calculated using ANOVA and were <0.001
for both trends.