Biomedical subjects

J Dillner

Publications and source records attributed to J Dillner.

At least 55 records · Page 3Linked to original sources

PubMed2000

A novel and rapid PCR-based method for genotyping human papillomaviruses in clinical samples.

Many human papillomavirus (HPV) genotypes are associated with cervical carcinoma. We demonstrate the utility of an innovative technique for genotyping of HPV in cervical tissue samples. This method provides an accurate means of identification of the specific HPV genotypes present in clinical specimens. By using the MY09-MY11 and the GP5(+)-GP6(+) consensus primer pairs, HPV sequences were amplified by nested PCR from DNA isolated from cervical smear samples. This led to the production of an approximately 140-bp PCR product from the L1 (major capsid) gene of any of the HPVs present in the sample. PCR was performed with a deoxynucleoside triphosphate mixture which resulted in the incorporation of deoxyuridine into the amplified DNA product at positions where deoxythymidine would normally be incorporated at a frequency of about once or twice per strand. Following the PCR, the product was treated with an enzyme mix that contains uracil N-glycosylase (UNG) and endonuclease IV. UNG removes the uracil base from the nucleotide, and endonuclease IV cleaves the phosphodiester bond at this newly formed abasic site, producing fragments of various sizes. By having end labeled one of the amplification primers, a DNA ladder which is analogous to a "T-sequencing ladder" was produced upon electrophoresis of the products. By comparing this T-sequencing ladder to the known sequences of HPVs, the genotypes of unknown HPV isolates in samples were assigned. Data showing the utility of this technique for the rapid analysis of clinical samples are presented.

Base Sequence↗

PubMed2000

Attack rates of human papillomavirus type 16 and cervical neoplasia in primiparous women and field trial designs for HPV16 vaccination.

BACKGROUND: Identification of human papillomavirus type 16 (HPV16) as the major risk factor for cervical neoplasia, and mass production of DNA free HPV capsids have paved the way to preventive vaccination trials. Design of such trials requires reliable attack rate data. OBJECTIVE: Determination of (1) HPV16 and (2) cervical neoplasia attack rates in primiparous women. Estimation of actuarial sample sizes for HPV16 vaccination phase IV trials. DESIGN: A longitudinal cohort study. METHODS: Population based Finnish Maternity Cohort (FMC) and Finnish Cancer Registry (FCR) were linked for the identification of two cohorts of primiparous women: (1) a random subsample of the FMC: 1656 women with two pregnancies between 1983-9 or 1990-6 and living in the Helsinki metropolitan area, and (2) all 72,791 primiparous women living in the same area during 1983-94. Attack rate for persistent HPV16 infection (1) was estimated in 1279 seronegative women by proportion of seroconversions between the first and the second pregnancy. Comparable 10 year cumulative incidence rate (CR) of cervical intraepithelial neoplasia grade III and cervical cancer (CIN III+) (2) was estimated based on cases registered at the FCR during 1991-4. RESULTS: The HPV16 attack rates were 13.8% (< 18 years), 7.0% (18-19 years), 2.3% (21 years), 2.4% (23 years), and 4.5% (< 25 years). Number of vaccinees required for a 5 year efficacy trial with persistent HPV16 infection as the end point ranged between 1000 and 3900, assuming 80% power, 90%-70% vaccine efficacy (VE), and misclassification. The CRs of CIN III+ were 0.33% (< 18 years), 0.44% (18-19 years), 0.21% (20-24 years), and 0.28% (< 25 years). Number of vaccinees required for a 10 year efficacy trial with HPV16 positive CIN III+ as the end point was 15,000 assuming 80% power, 90% VE, and 75% aetiological fraction of CIN III+ for HPV16. CONCLUSIONS: The attack rates of HPV16 and CIN III+ identify primiparous women under 25 years of age among target populations for postnatal HPV vaccination at phase II/III trials.

Adolescent↗

PubMed2000

Correlates of the spread of human papillomavirus infection.

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.

Adolescent↗

PubMed2000

Tumor necrosis factor a-11 and DR15-DQ6 (B*0602) haplotype increase the risk for cervical intraepithelial neoplasia in human papillomavirus 16 seropositive women in Northern Sweden.

HLA genes have been shown to be associated with cervical intraepithelial neoplasia (CIN), a precursor of cervical cancer. The human papillomaviruses (HPV) types 16 and 18 are the major environmental cause of this disease. Because the immune system plays an important role in the control of HPV infection, the association of polymorphic HLA could lead to a different immune response to control the development of cervical cancer. The aim of this study was to analyze the association between CIN and a microsatellite polymorphism of tumor necrosis factor (TNFa) taking HPV exposure and CIN-associated HLA haplotypes into account. In a nested case-control study in northern Sweden, 64 patients and 147 controls matched for age and sex and derived from the same population-based cohort were typed for TNFA, HLA-DR, and DQ and assayed for antibodies to HPV types 16 and 18. TNFa polymorphism was not associated with CIN per se. However, there was a significant increase in the frequency of TNFa-11 among HPV16-positive and HLA DR15-DQ6 (B*0602) patients compared with HPV16- and HLA-DQ6-negative patients (odds ratios, 5.4 and 9.3, respectively). The relative risk for CIN conferred by the combination of TNFa-11, HLA-DQ6, and HPV 16 positivity was 15. Our study suggests that the TNFa-11 allele is associated with HPV16 infection and associated with CIN in combination with HLA-DQ6 but not by itself.

Adult↗

PubMed2000

Epidemiology of human papillomavirus infection.

Anogenital human papillomavirus (HPV) infection is a sexually transmitted disease (STD) that typically follows a self-limiting transient course for both sexes. The HPV incidences and prevalences vary greatly, because they reflect the sexual activity of the individuals studied and of the population they are in contact with. Higher prevalences are seen in young, sexually active groups and in high-risk areas for cervical and penile cancer, e.g. in Colombia. There has also been an increasing trend with time in Western Europe, paralleling the spread of other STDs and changes in sexual behavior. Penile intraepithelial neoplasia is usually positive for high-risk HPV DNA, mostly of type 16, whereas only approximately 50% of invasive penile cancers are positive for HPV DNA. This is similar to the role of high-risk HPV in vulvar carcinoma, where the attributable proportion is also approximately 40-50%. Moreover, in both sites similar histologic types of squamous cell carcinoma, i.e. the basoloid and basaloid/warty types, are mainly associated with high-risk HPV types. The studies performed so far have indicated that HPV has an etiological role in penile cancer, although the attributable proportion may be only approximately 40-50%.

Carcinoma, Squamous Cell↗

PubMed1999

Type-specific persistence of human papillomavirus DNA before the development of invasive cervical cancer.

BACKGROUND: Infection with the human papillomavirus (HPV) has been established as a cause of cervical cancer, but the association between a positive test for HPV DNA and the risk of the subsequent development of invasive cervical cancer is unknown. METHODS: In a study of women who participated in a population-based screening program for cancer of the cervix in Sweden from 1969 to 1995, we compared the proportion of normal cervical smears (Pap smears) that were positive for HPV DNA among 118 women in whom invasive cervical cancer developed an average of 5.6 years later (range, 0.5 month to 26.2 years) with the proportion of HPV DNA-positive smears from 118 women who remained healthy during a similar length of follow-up (controls). The control women were matched for age to the women with cancer, and they had had two normal Pap smears obtained at time points that were similar to the times of the baseline smear and the diagnosis of cancer confirmed by biopsy in the women with cancer. RESULTS: At baseline, 35 of the women with cancer (30 percent) and 3 of the control women (3 percent) were positive for HPV DNA (odds ratio, 16.4; 95 percent confidence interval, 4.4 to 75.1). At the time of diagnosis, 80 of the 104 women with cancer for whom tissue samples were available (77 percent) and 4 of the 104 matched control women (4 percent) were positive for HPV DNA. The HPV DNA type was the same in the base-line smear and the biopsy specimen in all of the women with cancer in whom HPV DNA was detected at base line. None of the control women had the same type of HPV in both smears. CONCLUSIONS: A single positive finding of HPV DNA in a Pap smear confers an increased risk of future invasive cervical cancer that is positive for the same type of virus as identified earlier.

Adenocarcinoma↗

PubMed1999

Salivary sIgA response in HIV-1 infection.

Local and systemic production of total and HIV-1 specific IgA was determined in whole saliva and serum from 45 HIV-1-infected individuals and 15 healthy controls. The antigenic domains important for sIgA and IgG binding, respectively, was investigated with epitope mapping using synthetic peptides of HIV-1 proteins. Decreased levels of total sIgA in saliva were found among patients with low CD4+ cell counts in advanced stages of acquired immunodeficiency. HIV-1 specific IgA response, predominantly directed to the envelope proteins, was found in saliva and serum also at later stages of disease. Analyses using peptide enzyme-linked immunosorbent assays (ELISA) showed that the sIgA antibody response in saliva was mainly directed to the V4 region (aa 385-409) and a more C-terminal part of the V3-region (aa 325-344) compared with the IgG response, which predominantly was directed to a more central part of the V3 loop (aa 308-325). A similar picture was seen for immunoglobulins of the two isotypes derived from serum. We have in this study shown IgA epitope-specific immune response within HIV-1 gp160, indicating that antibodies of IgA isotype may recognize somewhat different antigenic domains compared to IgG antibodies.

Acquired Immunodeficiency Syndrome↗

PubMed1999

No excess risk of cervical carcinoma among women seropositive for both HPV16 and HPV6/11.

Human papillomavirus (HPV) types 16 and 18 are the major risk factors for cervical carcinoma, whereas HPV types 6 and 11 cause benign genital lesions. We wanted to study the joint effect of simultaneous infections with the oncogenic and non-oncogenic HPV types on risk of subsequent development of cervical carcinoma. A cohort of 530,000 women who had donated blood samples to Nordic serum banks between 1973 and 1994 was followed up by linkage to national cancer registries. We identified 182 prospective cases with invasive cervical carcinoma and selected 538 matched controls at random. HPV 6, 11, 16, 18 and 33 seropositivity was used as a marker for the different HPV infections, and seropositivity for Chlamydia trachomatis and cotinine were used as markers for risk-taking sexual behavior and smoking respectively. The adjusted odds ratio (OR) of cervical squamous-cell carcinoma (SCC) was 2.2 for HPV6/11 among HPV16 seronegatives and 5.5 for HPV16 among HPV6/11 seronegatives. Assuming multiplicative joint effect, the expected OR for seropositivity to both HPV6/11 and HPV16 would have been 12, but the observed OR was 1.0. The antagonistic interaction was statistically significant (p = 0.001) and present also under deterministic considerations of possible misclassification bias. Antagonistic interactions were also detected for combinations of HPV16 and HPV18 and of HPV16 and HPV33. The results are in line with the concept that HPV-specific immunity protects against SCC and support primary prevention of SCC by vaccination against the HPVs.

Adult↗

PubMed1999

A survey of seroprevalence of human papillomavirus types 16, 18 and 33 among children.

The importance and natural history of HPV infections in childhood is incompletely understood. We performed a survey for presence of serum antibodies to HPV capsids among 1031 children aged 0 to 13 years, resident in Stockholm, Sweden. The HPV seroprevalence among these children was 3.0% for HPV16, 0.6% for HPV18 and 2.7% for HPV33. By comparison, among simultaneously analyzed positive control panels comprising women with CIN or healthy women with type-specific cervical HPV DNA, seroprevalence of HPV 16, 18 and 33 was 69%, 58% and 63% respectively. The results suggest that HPV infection in childhood is not common.

Adolescent↗

PubMed1999

Human papillomavirus infection and esophageal cancer: a nationwide seroepidemiologic case-control study in Sweden.

BACKGROUND: Infection with human papillomavirus (HPV) type 16 has been implicated as a risk factor for esophageal squamous cell carcinoma in three seroepidemiologic studies. We conducted a larger, population-based study to verify this association and to investigate possible confounding factors. METHODS: We performed a nationwide case-control study in Sweden of HPV16 or HPV18 infection and risk of esophageal squamous cell carcinoma or esophageal/gastroesophageal adenocarcinoma. Tumors were strictly classified by their location and histologic type. Case subjects with incident cancers and population-based control subjects donated blood samples and were interviewed in person about potential confounding factors. An enzyme-linked immunosorbent assay was used to detect HPV seropositivity. Multivariate analyses were conducted to study relationships between HPV seropositivity, level of education, smoking (all tobacco) status, alcohol consumption, and cancer risk. RESULTS: We compared 121 case subjects with esophageal squamous cell carcinoma and 173 case subjects with adenocarcinoma of the esophagus or gastroesophageal junction with 302 population-based control subjects. The age- and sex-adjusted odds ratios (ORs) for squamous cell carcinoma were 1.0 (95% confidence interval [CI] = 0.5-2.0) for persons seropositive for HPV16 and 0.5 (95% CI = 0.2-1.1) for persons seropositive for HPV18 in comparison with seronegative individuals. The corresponding ORs for adenocarcinoma were 1.2 (95% CI = 0.7-2.2) and 0.2 (95% CI = 0.1-0.7), respectively. Adjustments for smoking status, alcohol consumption, and level of education did not alter the results. CONCLUSIONS: We found no evidence of a positive association between HPV16 or HPV18 infection and either form of esophageal cancer. Our results do not support conclusions from previous studies.

Adenocarcinoma↗

PubMed1999

The serological response to papillomaviruses.

The antibody response to papillomaviruses is a key determinant of protective immunity. HPV serology is also an important epidemiological tool for the assay of past and present HPV infections and for prediction of HPV-associated cancers and their precursor lesions. This review focuses on the assay of antibody responses to the HPV capsid, its use as a marker of cumulative HPV exposure and surveys how HPV seroepidemiology has been used to elucidate the spread of HPV infection in various populations, the natural history of HPV infection and that exposure to HPV is associated with increased risk for several human cancers.

Antibodies, Viral↗

PubMed1999

MICA gene polymorphism and the risk to develop cervical intraepithelial neoplasia.

Cervical intraepithelial neoplasia (CIN) is associated with human papillomaviruses (HPV) and the HLA genes. The MICA (MHC class I chain-related gene A) is expressed by keratinocytes and epithelial cells and interacts with gamma delta T cells. It is therefore possible that MICA might influence the pathogenesis of CIN and cervical cancer through presentation of viral or tumor antigens. To investigate this, we determined the MICA transmembrane allele frequencies in a prospective population-based cohort study from the Västerbotten County in northern Sweden. 74 women developed CIN. 153 control women who remained healthy during follow up were matched for age. Five polymorphic microsatellite alleles of MICA were identified by a polymerase chain reaction-based (PCR) technique using fluorescent-labeled primers. MICA A5 and A5.1 were the most common alleles in this population. None of the alleles of MICA were associated with disease. The frequency of MICA allele A5 was higher among HPV 18 seropositive than HPV 18 seronegative patients but this difference was not significant after the correction of p value. In conclusion, microsatellite allele polymorphism of MICA transmembrane part is not associated with cervical intraepithelial neoplasia.

Exons↗

PubMed1999

Serum antibodies against p53 in relation to cancer risk and prognosis in breast cancer: a population-based epidemiological study.

To perform an epidemiological evaluation of the predictive value of p53 autoantibodies in breast cancer, we measured antibodies against p53 in serum samples from 165 breast cancer patients in comparison with serum samples from 330 healthy controls, selected from the same population as the cases and matched for age, sex and specimen storage time. Median age of patients was 51 years (range 25-64 years). Presence of serum p53 autoantibodies was analysed by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blotting. The lower ELISA reactivities were similar for cases and controls, but presence of high-level reactivity was more common among cases than among controls [odds ratio (OR) 9.03, 95% confidence interval (CI) 2.40-50.43]. Presence of Western blot-detected p53 autoantibodies had a very similar association (OR 10.8, CI 3.0-59.4). Among the cases, we also studied whether there was any correlation between level of anti-p53 antibodies and stage of the disease or survival. There was no significant correlation between presence of antibodies and stage of the disease. There was a significant negative correlation between presence of p53 antibodies and survival (P = 0.003). A stepwise multivariate Cox regression analysis showed that T-stage, age and presence of anti-p53 antibodies were significant independent prognostic variables, with a dose-dependent negative effect on survival for all three variables. We conclude that presence of anti-p53 antibodies are of significance both for the risk of having breast cancer and the risk of dying from breast cancer.

Adult↗

PubMed1999

Human serum antibodies to a major defined epitope of human herpesvirus 8 small viral capsid antigen.

The major antibody-reactive epitope of the small viral capsid antigen (sVCA) of human herpesvirus 8 (HHV-8) was defined by use of overlapping peptides. Strong IgG reactivity was found among approximately 50% of 44 human immunodeficiency virus-positive or -negative patients with Kaposi's sarcoma and 13 subjects who were seropositive by immunofluorescence assay (IFA) for the latent HHV-8 nuclear antigen. Only 1 of 106 subjects seronegative for both lytic and latent HHV-8 antigens and 10 of 81 subjects IFA-seropositive only for the lytic HHV-8 antigen had strong IgG reactivity to this epitope. Among 534 healthy Swedish women, only 1.3% were strongly seropositive. Comparison of the peptide-based and purified sVCA protein-based ELISAs found 55% sensitivity and 98% specificity. However, only 1 of 452 serum samples from healthy women was positive in both tests. In conclusion, the defined sVCA epitope was a specific, but not very sensitive, serologic marker of active HHV-8 infection. Such infection appears to be rare among Swedish women, even with sexual risk-taking behavior.

Adolescent↗

PubMed1999

Sexual behaviour and papillomavirus exposure in cervical intraepithelial neoplasia: a population-based case-control study.

Sexual history is an established risk determinant for cervical neoplasia. It is not clear if human papillomavirus (HPV) exposure entirely explains the sexual behaviour-related risk or if other sexually transmitted agents may act as cofactors for HPV in carcinogenesis. The aim of this study was to elucidate whether HPV exposure or HPV persistence explains the sexual history-related risk of high-grade cervical intraepithelial neoplasia (CIN) using a population-based case-control study of most of the 254 women referred to colposcopy in the Vasterbotten county in Sweden because of an abnormal cervical smear during October 1993 to December 1995 and 320 age-matched women from the general population. The women were interviewed for sexual history and tested for presence of serum antibodies to HPV-16, -18 and -33 as well as for presence of HPV DNA in cervical brush samples. HPV-16, -18 and -33 seropositivity was specific for the corresponding type of HPV DNA, dependent on the lifetime sexual history and associated with a two- to threefold increased risk of CIN 3. There was no sexual history-related risk of CIN among HPV-seropositive women and adjustment for HPV DNA presence explained the sexual history-related risk of CIN. In conclusion, HPV exposure appeared to explain the sexual history-related risk of high-grade CIN.

Adult↗

PubMed1999

Immune responses against human papillomavirus (HPV) type 16 virus-like particles in a cohort study of women with cervical intraepithelial neoplasia. II. Systemic but not local IgA responses correlate with clearance of HPV-16.

To investigate whether there is an association between local or systemic IgG and IgA responses against human papillomavirus (HPV) type 16 virus-like particles (VLP) containing L1 and L2 and the possible influence of these responses on clearance of HPV-16 and its associated lesions, cervical mucus samples from 125 patients and plasma samples from 100 patients, all participating in a non-intervention cohort study of women with abnormal cytology, were analysed. The results show that local IgG and IgA HPV-16 VLP-specific antibodies do not correlate with virus clearance. However, systemic IgG responses were more frequently detected in patients with a persistent infection (11/24) compared with patients with cleared HPV-16 infections (3/28, P = 0.006). Furthermore, the ultimate development of high-grade lesions was associated with systemic VLP-specific IgG reactivity (P = 0.026). By contrast, systemic IgA responses were correlated with virus clearance (7/28 clearance compared with 1/24 persistence patients, P = 0.06). This correlation was statistically significant when only those clearance patients who tested HPV-16 DNA-positive at more than one visit were included in the analysis (5/11 compared with 1/24, P = 0.007). As these systemic IgA responses were not accompanied by local IgA responses, the systemic IgA responses in HPV-16 clearance patients are suggested to be a by-product of a successful cellular immune response induced at the local lymph nodes, mediated by cytokines.

Adolescent↗

PubMed1999

Reliable high risk HPV DNA testing by polymerase chain reaction: an intermethod and intramethod comparison.

BACKGROUND: The development of a reproducible, sensitive, and standardised human papillomavirus (HPV) polymerase chain reaction (PCR) test is required to implement HPV testing in cervical cancer screening programmes and for triaging women with mild to moderate dysplasia. AIMS: To determine the intermethod agreement between different GP5+/6+ and MY09/11 PCR based protocols for the detection and typing of high risk (HR) HPV DNA in cervical smears and to assess the intramethod reproducibility of the GP5+/6+ PCR enzyme immunoassay (EIA) for HR-HPV detection. METHODS: For the intermethod comparison, crude aliquots of 20 well characterised cervical smears comprising five HPV negative samples, and six and nine samples containing single and multiple HPV infections, respectively, were coded and sent from reference laboratory (A) to three other laboratories. One of these (laboratory B) used the GP5+/6+ PCR-EIA and was provided with standard protocols. Another laboratory (C) used GP5+/6+ PCR combined with sequence analysis and type specific PCR, whereas two laboratories (D and E) used MY09/11 PCR followed by restriction fragment length polymorphism (RFLP) analysis for the detection and typing of HR-HPV. The intramethod agreement of GP5+/6+ PCR-EIA was analysed in a subsequent study with four other laboratories (F to I) on crude aliquots of 50 well characterised cervical smears, consisting of 32 HR-HPV positive and 18 HPV negative samples. Standardised protocols, primers, and probes were also provided by the reference laboratory for HR-HPV detection. RESULTS: In the intermethod comparison, pairwise agreement of the different laboratories with reference laboratory A for the detection of HR-HPV varied between 75% and 100% (kappa values: 0.5 to 1). Typing data revealed a broader range in pairwise agreement rates between 32% and 100%. The highest agreement was found between laboratories A and B using standardised protocols and validated reagents. In the intramethod evaluation, pairwise comparison of the laboratories F to I with reference laboratory A revealed excellent agreement rates from 92% to 100% (kappa values: 0.88 to 1.0) with an overall sensitivity of 97.5% (195/200) and specificity of 99.5% (199/200). CONCLUSIONS: The detection of HR-HPV as a group is highly reproducible with GP5+/6+ PCR-EIA provided that standardised protocols and validated reagents are used.

Cervix Uteri↗

PubMed1999

Low levels of serum vitamins A and E in blood and subsequent risk for cervical cancer: interaction with HPV seropositivity.

Nutritional factors have been associated with risk of cervical cancer, but it is unclear whether the associations are of etiological significance or secondary to human papillomavirus (HPV) exposure. A delineation of this question requires a prospective study with invasive cancer as the end point. We conducted a nested case-control study in Finland and Sweden within a joint cohort of 405,000 women followed up for, on average, 4 years. Blood samples from 38 prospective cases of invasive cervical cancer diagnosed between 1985 and 1994 and 116 controls matched for age, country, and sample storage time were available for the study. Levels of retinol or unoxidized alpha-tocopherol in the blood were not risk factors for cervical cancer. However, joint-effect analysis of low levels of retinol disclosed statistically significant (p = 0.023) synergistic (more than multiplicative) interaction with HPV (HPV16, HPV18, or HPV33) seropositivity (observed relative risk = 2.6, 95% confidence interval = 0.7-8.8, expected relative risk = 0.3). Retinol might act as an effect modifier of the HPV-associated risk for cervical cancer; exposed women may require adequate levels for immunologic surveillance of HPV.

Adult↗