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Laura A Koutsky

Publications and source records attributed to Laura A Koutsky.

At least 19 recordsLinked to original sources
PubMed2007

Concordance of self-collected and clinician-collected swab samples for detecting human papillomavirus DNA in women 18 to 32 years of age.

OBJECTIVE: The objective of this study was to determine whether self- and clinician-collected samples are comparable for human papillomavirus (HPV) detection. STUDY DESIGN: Three hundred seventy-four women aged 23 to 32 (population 1) and 211 women aged 18 to 25 (population 2) contributed self-collected vaginal and clinician-collected cervical and vulvovaginal samples for HPV DNA testing. Eighty-six women mailed in self-collected samples. RESULTS: Agreement between self-collected vaginal and clinician-collected combined cervical/vulvovaginal samples was excellent (population 1:92.0%, kappa = 0.81; population 2: 96.4%, kappa = 0.88), but self-collected samples were more concordant with clinician-collected cervical samples in population 2 (kappa = 0.84) than population 1 (kappa = 0.65) (P = 0.01). Age-adjusted HPV prevalence was slightly lower in mailed-in (21.5%) than in-clinic self-collected samples (26.8%). CONCLUSIONS: The combined clinician-collected cervical/vulvovaginal sample is most sensitive for detecting all female genital tract HPV infections. HPV concordance between cervical and vaginal samples may be better for newer infections. Larger studies are needed to determine whether mailed-in self-samples are as effective as those collected in a clinical setting.

Adolescent↗
PubMed2007

Risk for high-grade cervical intraepithelial neoplasia associated with variants of human papillomavirus types 16 and 18.

BACKGROUND: Although the variant lineages of human papillomavirus (HPV) types 16 and 18 are well established, their individual associations with high-grade cervical intraepithelial neoplasia (CIN) have not been extensively evaluated. METHODS: Study subjects were women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study who were positive for HPV16 or HPV18 at enrollment. These women were followed every 6 months for 2 years. Viral isolates from enrollment samples were characterized by DNA sequencing and classified as variant lineages. RESULTS: Over a 2-year study period, CIN3 was histologically diagnosed in 291 of the 779 HPV16-positive women and 47 of the 275 HPV18-positive women. Among women without CIN2-3 at enrollment, the risk of subsequent CIN3 was 2.7-fold greater for those with HPV16 African-2 [95% confidence interval (95% CI), 1.0-7.0] and 3.1-fold greater for those with HPV16 Asian American (95% CI, 1.6-6.0), compared with European variants. Relative to infection with HPV18 African variants, the risk associating subsequent CIN3 was 3.8 (95% CI, 0.9-17.2) for infection with HPV18 European variants and 4.8 (95% CI, 1.0-23.6) for infection with HPV18 Asian American variants. Similar associations were observed when the 2-year prevalence of CIN3 was used as the end point. Further, for those with HPV16 European variants, the 2-year prevalence of CIN3 was higher in White women than in African American women (P = 0.01); this trend was reversed for those with HPV16 African-1 variants (P = 0.22). A similar pattern was present for infections with HPV18 European versus African variants. CONCLUSIONS: The lineages of HPV16 and HPV18 variants are associated with differing risks for high-grade CIN.

Adolescent↗
PubMed2006

Human papillomavirus type 16 and 18 variants: race-related distribution and persistence.

BACKGROUND: Analogous to the geographic distribution of variants of human papillomavirus (HPV) types, the distribution and persistence of these variants among infected individuals may be related to the racial composition of a population living in one geographic region. METHODS: We studied 1114 women in the United States participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study who were positive for HPV16 and/or HPV18 at enrollment. Race was self-reported. HPV samples were characterized by sequencing the E6 gene and part of the long control region and classified as variants according to established lineages. Subjects were examined for HPV every 6 months for 2 years. All statistical tests were two-sided. RESULTS: HPV18 African variants were predominant in the 97 HPV18-infected African American women (i.e., 62 women or 63.9%, 95% confidence interval [CI] = 53.5% to 73.4%), and European variants were common in the 168 HPV18-infected white women (i.e., 91 women or 54.2%, 95% CI = 46.3% to 61.9%). HPV16 African variants accounted for 43 (26.5%, 95% CI = 19.9% to 34.0%) of the infections in the 162 HPV16-infected African American women but for only 25 (4.3%, 95% CI = 2.8% to 6.3%) in the 584 HPV16-infected white women. The likelihood of remaining HPV18 positive was statistically significantly higher in white women infected with European than in white women infected with African variants (P = .04); the reverse was observed in African American women (P = .03). A similar pattern was observed for persistence of HPV16 variants, with the likelihood of remaining positive being higher for white women, but lower for African American women, infected with an European variant than with an African variant (P = .03 and P = .16, respectively). CONCLUSIONS: Variants of HPV16 and HPV18 appear to persist longer in a host whose race indicates an ancestral geographic distribution that was once shared with that of the variant-i.e., European variants persist longer in white women, and African variants persist longer in African American women.

Adult↗
PubMed2006

Chapter 13: Current findings from prophylactic HPV vaccine trials.

Early data from randomized controlled trials consistently show that prophylactic human papillomavirus virus-like particle (HPV VLP) vaccines are effective in preventing infection and lesions caused by the targeted HPV type(s). Two vaccines, a bivalent HPV-16/18 VLP vaccine and a quadrivalent HPV-6/11/16/18 VLP vaccine, are currently undergoing evaluation in phase III trials with anticipation of receiving regulatory approval for use in immunization programs worldwide. Both vaccines have the potential to substantially reduce HPV-related morbidity and mortality. This review focuses on published data from clinical trials of these two vaccines.

Adolescent↗
PubMed2006

Condom use and the risk of genital human papillomavirus infection in young women.

BACKGROUND: To evaluate whether the use of male condoms reduces the risk of male-to-female transmission of human papillomavirus (HPV) infection, longitudinal studies explicitly designed to evaluate the temporal relationship between condom use and HPV infection are needed. METHODS: We followed 82 female university students who reported their first intercourse with a male partner either during the study period or within two weeks before enrollment. Cervical and vulvovaginal samples for HPV DNA testing and Papanicolaou testing were collected at gynecologic examinations every four months. Every two weeks, women used electronic diaries to record information about their daily sexual behavior. Cox proportional-hazards models were used to evaluate risk factors for HPV infection. RESULTS: The incidence of genital HPV infection was 37.8 per 100 patient-years at risk among women whose partners used condoms for all instances of intercourse during the eight months before testing, as compared with 89.3 per 100 patient-years at risk in women whose partners used condoms less than 5 percent of the time (adjusted hazard ratio, 0.3; 95 percent confidence interval, 0.1 to 0.6, adjusted for the number of new partners and the number of previous partners of the male partner). Similar associations were observed when the analysis was restricted to high-risk and low-risk types of HPV and HPV types 6, 11, 16, and 18. In women reporting 100 percent condom use by their partners, no cervical squamous intraepithelial lesions were detected in 32 patient-years at risk, whereas 14 incident lesions were detected during 97 patient-years at risk among women whose partners did not use condoms or used them less consistently. CONCLUSIONS: Among newly sexually active women, consistent condom use by their partners appears to reduce the risk of cervical and vulvovaginal HPV infection.

Adolescent↗
PubMed2006

Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18.

Human papillomavirus (HPV) infection causes cervical cancer and genital warts. Young women (1106) were randomized to receive one of three formulations of a quadrivalent HPV (Types 6/11/16/18) L1 virus-like particle (VLP) vaccine or one of two placebo formulations. The goal was to assess vaccine safety and immunogenicity in baseline HPV 6/11/16 or 18-naïve and previously infected subjects. All three formulations were highly immunogenic. At Month 2 (postdose 1), among women with vaccine-type antibodies at baseline, vaccine-induced anti-HPV responses were approximately 12- to 26-fold higher than those observed in baseline-naïve women, suggesting an anamnestic response. Following an initial, similar sized decline, anti-HPV responses plateaued and remained stable through end-of-study (3.0 years). No vaccine-related serious adverse experiences were reported.

Adolescent↗
PubMed2006

Genital human papillomavirus infection in men.

Genital human papillomavirus (HPV) infection, globally one of the most common sexually transmitted infections, is associated with cancers, genital warts, and other epithelial lesions. Although a consistent and coherent picture of the epidemiology and pathogenesis of genital HPV infections in women has developed over the past two decades, less is known about these infections in men. Available data suggest that, as with women, most genital HPV infections in men are symptomless and unapparent, and that HPV16 is probably the most frequently detected type. In populations of similar age, the prevalence of specific HPV types is usually lower in men than in women. Whether this observation relates to lower incidence or shorter duration of infection in men than in women has not yet been determined. Seroprevalence of specific anti-HPV antibodies also seems to be lower in men than in women of similar age, a difference that might be due to lower viral load, lower incidence or duration of infection or lower antibody responses, or both, in men compared with women. Differences in sexual behaviour may also be important predictors of genital HPV infection. With the anticipated availability of prophylactic HPV vaccines in the near future, it becomes increasingly important to understand the incidence and duration of HPV infections in men to develop cost-effective approaches to prevention through a combination of immunisation and promotion of risk-reduction strategies.

Condylomata Acuminata↗
PubMed2006

Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: a randomized controlled trial.

OBJECTIVE: Human papillomavirus (HPV) virus-like particle (VLP) vaccines have demonstrated effectiveness in preventing persistent HPV infections. Whether protection lasts longer than 18 months and, thus, impacts rates of cervical intraepithelial neoplasia (CIN) 2-3 has not yet been established. We present results from an HPV16 L1 VLP vaccine trial through 48 months. METHODS: A total of 2,391 women, aged 16-23 years, participated in a randomized, double-blind, placebo-controlled trial. Either 40 mug HPV16 L1 VLP vaccine or placebo was given intramuscularly at day 1, month 2, and month 6. Genital samples for HPV16 DNA and Pap tests were obtained at day 1, month 7, and then 6-monthly through month 48. Colposcopy and cervical biopsies were performed if clinically indicated and at study exit. Serum HPV16 antibody titer was measured by radioimmunoassay. RESULTS: Among 750 placebo recipients in the per protocol population, 12 women developed HPV16-related CIN2-3 (6 CIN2 and 6 CIN3). Among 755 vaccine recipients, there were no cases (vaccine efficacy 100%, 95% confidence interval [CI] 65-100%). There were 111 cases of persistent HPV16 infection in placebo recipients and 7 cases in vaccine recipients (vaccine efficacy 94%, 95% CI 88-98%). After immunization, HPV16 serum antibody geometric mean titers peaked at month 7 (1,519 milli-Merck units [mMU]/mL), declined through month 18 (202 mMU/mL), and remained relatively stable between month 30 and month 48 (128-150 mMU/mL). CONCLUSION: The vaccine HPV16 L1 VLP provides high-level protection against persistent HPV16 infection and HPV16-related CIN2-3 for at least 3.5 years after immunization. Administration of L1 VLP vaccines targeting HPV16 is likely to reduce risk for cervical cancer. LEVEL OF EVIDENCE: I.

Adolescent↗
PubMed2006

Human papillomavirus infection among sexually active young women in the United States: Implications for developing a vaccination strategy.

OBJECTIVES: Population-level data on prevalence and distribution of human papillomavirus (HPV) types in the United States are necessary to guide optimal vaccination strategies. STUDY: Urine specimens from 3262 women ages 18 to 25 in the National Longitudinal Study of Adolescent Health (Wave III) were tested and typed for HPV. Poststratification sampling weights generated nationally representative estimates. RESULTS: Overall HPV prevalence was 26.9% and as high as 14.3% among women with 1 lifetime partner but did not vary by geographic region. High-risk types were detected in 20%; approximately 10% were infected with types in current candidate vaccines. HPV infection was independently associated with mixing sex with alcohol, a black partner, >3 lifetime sex partners, being single, and illegal drug use. Having a current sex partner and receptive oral sex were inversely associated with HPV. CONCLUSION: HPV prevalence was high throughout the country, even among women with only 1 lifetime partner, suggesting early and widespread rather than targeted immunization of young women.

Adolescent↗
PubMed2006

Identification of human papillomavirus type 16 L1 surface loops required for neutralization by human sera.

The variable surface loops on human papillomavirus (HPV) virions required for type-specific neutralization by human sera remain poorly defined. To determine which loops are required for neutralization, a series of hybrid virus-like particles (VLPs) were used to adsorb neutralizing activity from HPV type 16 (HPV16)-reactive human sera before being tested in an HPV16 pseudovirion neutralization assay. The hybrid VLPs used were composed of L1 sequences of either HPV16 or HPV31, on which one or two regions were replaced with homologous sequences from the other type. The regions chosen for substitution were the five known loops that form surface epitopes recognized by monoclonal antibodies and two additional variable regions between residues 400 and 450. Pretreatment of human sera, previously found to react to HPV16 VLPs in enzyme-linked immunosorbent assays, with wild-type HPV16 VLPs and hybrid VLPs that retained the neutralizing epitopes reduced or eliminated the ability of sera to inhibit pseudovirus infection in vitro. Surprisingly, substitution of a single loop often ablated the ability of VLPs to adsorb neutralizing antibodies from human sera. However, for all sera tested, multiple surface loops were found to be important for neutralizing activity. Three regions, defined by loops DE, FG, and HI, were most frequently identified as being essential for binding by neutralizing antibodies. These observations are consistent with the existence of multiple neutralizing epitopes on the HPV virion surface.

Animals↗
PubMed2006

Smokers at higher risk for undetected antibody for oncogenic human papillomavirus type 16 infection.

OBJECTIVE: To determine the association between tobacco smoking and serologic evidence of human papillomavirus type 16 (HPV16)-specific antibodies among HPV16 DNA-positive women. DESIGN, SETTING, AND PARTICIPANTS: Baseline health history, physical examination, and laboratory data for 205 HPV16 DNA-positive women with no prior cytologic evidence of squamous intraepithelial lesions who were enrolled subsequently in a randomized clinical trial. MAIN OUTCOME MEASURE: HPV16-L1 antibody (anti-HPV16 antibody) detected from serum using RIA or ELISA. RESULTS: Eighty-seven percent (179 of 205) of women tested positive for HPV16 DNA using cervicovaginal swabs or lavage specimens, and 26 women showed similar results using swab specimens of external genitalia alone. HPV16-infected women who reported increasingly greater levels of daily cigarette smoking were less likely to test positive for anti-HPV16 antibodies than nonsmoking women (P = 0.02). Smokers were twice as likely as nonsmokers to test negative for anti-HPV16 antibodies, even after controlling for the effects of other covariates in the analyses (adjusted odds ratio, 0.5; 95% confidence limits, 0.2-0.9). Although Papanicolaou test findings and smoking characteristics were poorly correlated (r(2) = 0.01), women who showed atypical cells of unknown significance or squamous intraepithelial lesion were twice as likely to test anti-HPV16 antibody positive as women who showed normal Papanicolaou tests (adjusted odds ratio, 2.0; 95% confidence limits, 1.1-3.7). CONCLUSION: These data suggest that smoking may influence the long-term risk for cancer by perturbing early immune responses to the virus and may increase the likelihood of persistent infection. Patient education messages should alert women to this additional risk of smoking. A clinical trial of smoking cessation should be explored as a therapeutic intervention for primary HPV16 infection.

Adolescent↗
PubMed2005

Comparison of oral fluid and serum ELISAs in the determination of IgG response to natural human papillomavirus infection in university women.

BACKGROUND: Venipuncture (phlebotomy) is an obstacle to subject recruitment and ongoing participation in cohort studies investigating human papillomavirus (HPV) infection. Anti-HPV antibodies are not only detected in serum but also in oral fluid. OBJECTIVES: To evaluate if oral fluid specimens can be used in lieu of blood specimens for determining HPV antibody status. STUDY DESIGN: One hundred and seven paired oral fluid and blood specimens from female university students were tested in a HPV16 ELISA and compared to sexual history and serial genital HPV16 DNA status. RESULTS: ELISA results were in agreement in 97% (104/107) of paired sera and oral fluid. Of six women with positive anti-HPV16 serum samples, only three had positive oral fluid specimens. However, the specificity of the oral fluid test was 100% compared to the blood test. CONCLUSIONS: Detection of antibodies in oral fluid correlated with antibodies but was less sensitive than sera. A larger validation study is required to fully characterize the oral fluid assay.

Antibodies, Viral↗
PubMed2005

Development and duration of human papillomavirus lesions, after initial infection.

BACKGROUND: To determine the potential value of human papillomavirus (HPV) vaccines, information concerning the incidence and duration of clinically important lesions is needed. METHODS: A total of 603 female university students were followed for a mean duration of 38.8 months. Triannual gynecologic examinations included cervical and vulvovaginal specimen collection for Pap and HPV DNA testing. Women with cytologic evidence of a high-grade squamous intraepithelial lesion (SIL) were referred for colposcopically directed biopsy. RESULTS: Among women with incident HPV infection, the 36-month cumulative incidence of cervical SILs found by cytologic testing (47.2%; 95% confidence interval [CI], 38.9%-56.4%) was higher than that of vaginal SILs (28.8%; 95% CI, 21.3%-38.2%). The median time to clearance of cervical and vaginal SILs was 5.5 and 4.7 months, respectively. Among women with incident HPV-16 or HPV-18 infection, the 36-month cumulative incidence of cervical intraepithelial neoplasia (CIN) grade 2 was 20.0% (95% CI, 10.8%-35.1%), and that of CIN grade 3 was 6.7% (95% CI, 2.5%-17.0%). The 36-month cumulative incidence of clinically ascertained genital warts among women with incident HPV-6 or HPV-11 infection was 64.2% (95% CI, 50.7%-77.4%). CONCLUSIONS: Intraepithelial lesions are common early events among women with incident HPV infection, and the interval between incident HPV-16 or HPV-18 infection and biopsy-confirmed CIN grade 2-3 appears to be relatively short.

Adolescent↗
PubMed2005

The epidemiology of human papillomavirus infections.

Infection with oncogenic human papillomavirus (HPV) types is a necessary cause of cervical cancer, the second most frequently occurring cancer in women worldwide. Rates of acquisition of HPV are high, particularly among sexually active young adults. Reported estimates of incident HPV infection among initially negative women have reached as high as 60% over a 5-year follow-up period. In this article, we review the epidemiology of HPV infection. In addition to estimates of disease frequency, we highlight risk factors for HPV infection, including the number of lifetime sex partners, which is the most salient risk factor. We discuss significant issues surrounding the natural history of HPV infection, including viral persistence versus clearance, immune response, development of lesions and development of cancer. Finally, we discuss strategies for preventing HPV infection.

Female↗
PubMed2005

Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial.

BACKGROUND: A randomised double-blind placebo-controlled phase II study was done to assess the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types associated with 70% of cervical cancers (types 16 and 18) and with 90% of genital warts (types 6 and 11). METHODS: 277 young women (mean age 20.2 years [SD 1.7]) were randomly assigned to quadrivalent HPV (20 microg type 6, 40 microg type 11, 40 microg type 16, and 20 microg type 18) L1 virus-like-particle (VLP) vaccine and 275 (mean age 20.0 years [1.7]) to one of two placebo preparations at day 1, month 2, and month 6. For 36 months, participants underwent regular gynaecological examinations, cervicovaginal sampling for HPV DNA, testing for serum antibodies to HPV, and Pap testing. The primary endpoint was the combined incidence of infection with HPV 6, 11, 16, or 18, or cervical or external genital disease (ie, persistent HPV infection, HPV detection at the last recorded visit, cervical intraepithelial neoplasia, cervical cancer, or external genital lesions caused by the HPV types in the vaccine). Main analyses were done per protocol. FINDINGS: Combined incidence of persistent infection or disease with HPV 6, 11, 16, or 18 fell by 90% (95% CI 71-97, p<0.0001) in those assigned vaccine compared with those assigned placebo. INTERPRETATION: A vaccine targeting HPV types 6, 11, 16, 18 could substantially reduce the acquisition of infection and clinical disease caused by common HPV types.

Adolescent↗
PubMed2005

Should liquid-based cytology be repeated at the time of colposcopy?

OBJECTIVE: To evaluate the usefulness of repeated liquid cytology at the time of colposcopy. MATERIALS AND METHODS: We screened 5,100 women with liquid-based cytology and human papillomavirus (HPV) DNA testing. Women with any abnormal cytology result including atypical squamous cells of undetermined significance (ASCUS) or a positive high-risk HPV DNA test result were referred for colposcopy. One thousand three hundred thirty-three women returned for colposcopy with repeated cytology and cervical biopsy. RESULTS: Twenty-one women had less than high-grade squamous intraepithelial lesion (HSIL) screening cytology and cervical biopsy results; however, their repeated cytology at the colposcopy visit revealed HSIL, and excisional treatment was recommended. Repeated cytology at colposcopy significantly changed the clinical management for 1.6% (21) of 1,333 women. CONCLUSIONS: As an adjunct test to colposcopy, liquid cytology was similar to conventional cytology. Given current practice patterns, repeated liquid cytology at the time of colposcopy is rarely clinically useful.

Adolescent↗
PubMed2005

Humoral immune response recognizes a complex set of epitopes on human papillomavirus type 6 l1 capsomers.

Although epitope mapping has identified residues on the human papillomavirus (HPV) major capsid protein (L1) that are important for binding mouse monoclonal antibodies, epitopes recognized by human antibodies are not known. To map epitopes on HPV type 6 (HPV6) L1, surface-exposed loops were mutated to the corresponding sequence of HPV11 L1. HPV6 L1 capsomers had one to six regions mutated, including the BC, DE, EF, FG, and HI loops and the 139 C-terminal residues. After verifying proper conformation, hybrid capsomers were used in enzyme-linked immunosorbent assays with 36 HPV6-seropositive sera from women enrolled in a study of incident HPV infection. Twelve sera were HPV6 specific, while the remainder reacted with both HPV6 and HPV11 L1. By preadsorption studies, 6/11 of these sera were shown to be cross-reactive. Among the HPV6-specific sera there was no immunodominant epitope recognized by all sera. Six of the 12 sera recognized epitopes that contained residues from combinations of the BC, DE, and FG loops, one serum recognized an epitope that consisted partially of the C-terminal arm, and three sera recognized complex epitopes to which reactivity was eliminated by switching all five loops. Reactivity in two sera was not eliminated even with all six regions swapped. The patterns of epitope recognition did not change over time in women whose sera were examined 9 years after their first-seropositive visit.

Antibody Specificity↗