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Diane M Harper

Publications and source records attributed to Diane M Harper.

16 recordsLinked to original sources
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

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

Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial.

BACKGROUND: Effective vaccination against HPV 16 and HPV 18 to prevent cervical cancer will require a high level of sustained protection against infection and precancerous lesions. Our aim was to assess the long-term efficacy, immunogenicity, and safety of a bivalent HPV-16/18 L1 virus-like particle AS04 vaccine against incident and persistent infection with HPV 16 and HPV 18 and their associated cytological and histological outcomes. METHODS: We did a follow-up study of our multicentre, double-blind, randomised, placebo-controlled trial reported in 2004. We included women who originally received all three doses of bivalent HPV-16/18 virus-like particle AS04 vaccine (0.5 mL; n=393) or placebo (n=383). We assessed HPV DNA, using cervical samples, and did yearly cervical cytology assessments. We also studied the long-term immunogenicity and safety of the vaccine. FINDINGS: More than 98% seropositivity was maintained for HPV-16/18 antibodies during the extended follow-up phase. We noted significant vaccine efficacy against HPV-16 and HPV-18 endpoints: incident infection, 96.9% (95% CI 81.3-99.9); persistent infection: 6 month definition, 94.3 (63.2-99.9); 12 month definition, 100% (33.6-100). In a combined analysis of the initial efficacy and extended follow-up studies, vaccine efficacy of 100% (42.4-100) against cervical intraepithelial neoplasia (CIN) lesions associated with vaccine types. We noted broad protection against cytohistological outcomes beyond that anticipated for HPV 16/18 and protection against incident infection with HPV 45 and HPV 31. The vaccine has a good long-term safety profile. INTERPRETATION: Up to 4.5 years, the HPV-16/18 L1 virus-like particle AS04 vaccine is highly immunogenic and safe, and induces a high degree of protection against HPV-16/18 infection and associated cervical lesions. There is also evidence of cross protection.

Adult↗
PubMed2005

Vaccination against human papillomavirus infection: a new paradigm in cervical cancer control.

Universal deployment of organized or opportunistic screening with Pap cytology in high and middle income countries has been the primary reason for the substantial reductions in cervical cancer morbidity and mortality during the last 50 years. However, in many low income countries Pap cytology screening is yet to be effectively implemented or has failed to reduce cervical cancer rates to an appreciable extent. Cervical cancer thus remains a critical public health problem that is second only to breast cancer in overall disease burden for women throughout the world. The fact that infection with certain human papillomavirus (HPV) types is now recognized as a necessary cause of this disease has led to new research fronts on the prevention of cervical cancer. Recent research on the safety and efficacy of candidate prophylactic vaccines against HPV have shown very promising results with nearly 100% efficacy in preventing the development of persistent infections and cervical precancerous lesions. Ongoing clinical studies are expected to provide further evidence of efficacy and will form the basis for licensing of candidate vaccines by the major pharmaceutical companies within 3-6 years. Although the future seems bright on the HPV vaccine front policy makers are strongly cautioned to avoid scaling back cervical cancer screening. It will take many years before we can rationally develop cervical cancer screening strategies that will be cost-effective for the proper surveillance of women protected by HPV vaccination.

Clinical Trials as Topic↗
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

How condom use, number of receptive anal intercourse partners and history of external genital warts predict risk for external anal warts.

Few analytic opportunities have allowed us to evaluate the role that specific sexual acts and male latex condoms play in the acquisition of external anal warts (EAW) using longitudinal data. The acquisition of EAWs occurs from epithelial contact with other HPV-infected surfaces, and hence is dependent upon sexual behaviour. Our objectives were to classify the relative importance of condom use, receptive anal intercourse (RAI) and prior history of EGWs on acquisition of EAWs. The observational Multicenter AIDS Cohort Study followed 2925 men over nine semiannual study visits for behavioural and physical examinations with laboratory testing. The main outcome measure was the occurrence of examiner-diagnosed EAWs in a homosexual population. EAWs were diagnosed among 10% of men studied across 22,157 visits reviewed for this study. Men with history of EGWs were more likely than those previously unaffected to have developed EAWs (cOR = 2.4 (2.0, 2.9)), as were men who reported multiple anoreceptive intercourse partners (e.g., compared with men who reported no RAI partners, men with 1, 2-5, > or = 6 RAI partners had crude risk ratios 1.0 (0.8, 1.3), 1.6 (1.2, 2.1), 3.9 (2.7, 5.8), respectively). These relations persisted after other demographic and sexual risk factors were controlled for in the analyses. Consistent condom usage showed no protective effect for EAWs in our crude or adjusted analyses. Patient education messages should be tailored to reflect our uncertainty about the protective nature of condoms for the development of anal warts, but to continue to assert the protective effects of a limited lifetime number of sexual partners and the heightened risk for wart recurrence once infected.

Anus Diseases↗
PubMed2004

Optical detection of high-grade cervical intraepithelial neoplasia in vivo: results of a 604-patient study.

OBJECTIVE: The purpose of this study was to assess the in vivo optical detection of high-grade cervical intraepithelial neoplasia (2/3+) on the whole cervix with a noncontact, spectroscopic device. STUDY DESIGN: Cervical scanning devices collected intrinsic fluorescence and broadband white light spectra and video images from 604 women during routine colposcopy examinations at 6 clinical centers. A statistically significant dataset was developed of intrinsic fluorescence and white light-induced cervical tissue spectra that was correlated to expert histopathologic determination. On the basis of a retrospective analysis of the acquired data, a classification algorithm was developed, validated, and optimized. RESULTS: Intrinsic fluorescence, backscattered white light, and video imaging each contribute complementary information to diagnostic algorithms for high-grade cervical neoplasia. More than 10000 measurements that were made on colposcopically identified tissue from >500 subjects were the basis for algorithm training and testing. Algorithm performance demonstrated a sensitivity of approximately 90%. This performance was confirmed by various training methods. With the use of a multivariate classification algorithm, optical detection is predicted to detect 33% more high-grade cervical intraepithelial neoplasia (2/3+) than colposcopy alone. CONCLUSION: Full cervix optical interrogation for the detection of high-grade cervical intraepithelial neoplasia is feasible and appears capable of detecting more high-grade cervical intraepithelial neoplasia than colposcopy alone. With the use of this classification algorithm, a multisite, randomized controlled trial is underway that compares the combination of optical detection and colposcopy versus colposcopy alone.

Adolescent↗
PubMed2004

Beyond the Pap: assessing patients' priorities for the annual examination.

PURPOSE: Recent cervical cancer screening technologies depend on biennial and triennial screening of cytologically normal women to be cost-effective. The guidelines for these technologies cannot be appropriately implemented if women demand continued cervical screening at their annual examinations. The purpose of this study was to identify the reasons for an annual examination that are important to women. METHODS: Age-specific focus groups elicited 22 consistently important reasons that were then incorporated into a survey given to northern New England women seeking healthcare. The reasons were classified as test-seeking reasons and as provider-patient relationship reasons. A distribution matrix of the test-seeking and provider-patient relationship reasons was constructed for paired McNemar chi-square analysis. Multivariate regression analyses compared the selected reasons to the women's demographic characteristics. RESULTS: There were 121 women from three distinct primary care offices who completed the surveys. Women were highly likely to chose patient-provider reasons as more important components of the annual examination than test-seeking reasons (chi-square for symmetry = 54.44, p < 0.001). The lesser importance of an annual Pap test did not vary by age, education level, and number of healthcare visits made in the last year. CONCLUSIONS: Our results indicate that northern New England women value the provider-patient relationship as paramount for the annual examination, thus supporting the notion that the biennial and triennial Pap intervals for cytologically normal women provided by the new cervical cancer screening technologies would be acceptable in this population.

Adult↗
PubMed2002

Randomized clinical trial of PCR-determined human papillomavirus detection methods: self-sampling versus clinician-directed--biologic concordance and women's preferences.

OBJECTIVE: The purpose of this study was to compare the high-risk human papillomavirus detection rates from self-sampled swabs and tampons with standard clinician-directed speculum sampling and to assess women's acceptance of self-sampling methods. STUDY DESIGN: One hundred three women who required a colposcopy underwent order randomization of the human papillomavirus sampling technique. Kappa and McNemar test statistical results were used to measure the agreement between clinician-directed and self-sampling techniques for high-risk types of human papillomavirus and the acceptance of self-sampling techniques. RESULTS: All self-directed samplings were equivalent to clinician sampling for all cervical intraepithelial neoplasia disease states. High-risk human papillomavirus was detected by self- and clinician-directed methods in 83% of the women with cervical intraepithelial neoplasia, grade 2/3. The 2 sequential swabs trend toward better detection of high-risk types of human papillomavirus than all other techniques for women with normal histologic factors (P =.0736, by McNemar's chi2 test). Ninety-four percent of women would accept self-sampling for their yearly cervical screen. CONCLUSION: Self-sampling is equivalent to clinician sampling for the detection of high-risk human papillomavirus and is acceptable to women as a yearly screen.

Adult↗
PubMed2002

Tampon samplings with longer cervicovaginal cell exposures are equivalent to two consecutive swabs for the detection of high-risk human papillomavirus.

BACKGROUND: Self-sampling for human papillomavirus (HPV) is useful for triage of ASCUS Papanicolaou (Pap) smears. Tampons with 10-second cervicovaginal cell exposure can detect HPV but appear to be less efficient than two consecutive swabs. GOAL: The purpose of this study was to evaluate increased vaginal tampon exposures for detecting high-risk HPV. STUDY DESIGN: This longitudinal cohort study followed women who self-sampled weekly with tampons for progressively longer periods of time. A tampon was inserted for 10 seconds at the office visit and 1 hour, 4 hours, and overnight for the three subsequent home samples. Two concurrent swabs were used with each tampon sampling for contemporaneous comparisons. The MY09/MY11 PCR primer system with reverse line blot detection strips was used to detect 18 distinct high-risk HPV types. RESULTS: Of the 309 tampons and 618 swabs used at home, 83% were returned. Among normal women, the 10-second tampon detected fewer with normal histology and high-risk HPV than did its swabs ( = 0.0412), but the 1-hour, 4-hour, and overnight tampons had high-risk-HPV detection rates equal to their swabs. In women with CIN, all tampons and swabs equally identified those with high-risk HPV. CONCLUSION: Self-sampling for HPV detection is acceptable, feasible, and technically accurate for both tampons with longer cervicovaginal exposures and swabs. The choice of technique is dependent on the woman, her culture, and her clinician.

Diagnosis, Differential↗
PubMedDate not supplied

Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial.

BACKGROUND: Vaccination against the most common oncogenic human papillomavirus (HPV) types, HPV-16 and HPV-18, could prevent development of up to 70% of cervical cancers worldwide. We did a randomised, double-blind, controlled trial to assess the efficacy, safety, and immunogenicity of a bivalent HPV-16/18 L1 virus-like particle vaccine for the prevention of incident and persistent infection with these two virus types, associated cervical cytological abnormalities, and precancerous lesions. METHODS: We randomised 1113 women between 15-25 years of age to receive three doses of either the vaccine formulated with AS04 adjuvant or placebo on a 0 month, 1 month, and 6 month schedule in North America and Brazil. Women were assessed for HPV infection by cervical cytology and self-obtained cervicovaginal samples for up to 27 months, and for vaccine safety and immunogenicity. FINDINGS: In the according-to-protocol analyses, vaccine efficacy was 91.6% (95% CI 64.5-98.0) against incident infection and 100% against persistent infection (47.0-100) with HPV-16/18. In the intention-to-treat analyses, vaccine efficacy was 95.1% (63.5-99.3) against persistent cervical infection with HPV-16/18 and 92.9% (70.0-98.3) against cytological abnormalities associated with HPV-16/18 infection. The vaccine was generally safe, well tolerated, and highly immunogenic. INTERPRETATION: The bivalent HPV vaccine was efficacious in prevention of incident and persistent cervical infections with HPV-16 and HPV-18, and associated cytological abnormalities and lesions. Vaccination against such infections could substantially reduce incidence of cervical cancer.

Adolescent↗
PubMedDate not supplied

Factors affecting the detection rate of human papillomavirus.

BACKGROUND: Maximizing the accuracy of human papillomavirus (HPV) detection from a single sample is important for clinical and research purposes. The purpose of this study was to determine whether cyclic hormonal variation, recent sexual intercourse, interval between samplings, and the technique used to sample affect the detection of HPV. METHODS: This study was a prospective, longitudinal, randomized controlled trial. Three techniques for self-sampling (2 consecutive synthetic polyester fiber [Dacron] swabs, a single Dacron swab, and a tampon) were repeated at 3 different sampling times during a period of 4 to 6 weeks in addition to 1 clinician-directed sampling of the ectocervix and endocervix at the first sampling time. All self-samplings were taken in a proscribed randomized order. Women (aged 18 to 68 years) attending a colposcopy clinic for abnormal cytology or abnormal cervical appearance participated in the study. The outcome measure was the detection of HPV by polymerase chain reaction amplification. RESULTS: The 103 participants provided 1,189 cervicovaginal samplings. Logistic regression indicated that intercourse within 48 hours of sampling did not result in a greater detection of high-risk or any HPV type (odds ratio [OR] = 1.05, 95% confidence interval [CI], 0.65-1.69; OR = 1.08, 95% CI, 0.73-1.60, respectively). Among those women who have regular menstrual cycles, there was no cyclic effect on HPV detection for high-risk and any HPV types. Time from previous sampling did not affect HPV detection. Among the self-sampling techniques, using a single self-swab and the tampon resulted in the detection of HPV between 10% and 35% less often than using 2 consecutive swabs (P < .025). Self-sampling with 2 swabs was not significantly different from clinician sampling for detecting high-risk HPV types (OR for self-sampling = 0.87 (95% CI, 0.66-1.13)). CONCLUSIONS: HPV detection is not dependent on menstrual cycle timings, the recency of intercourse, or the time between samplings, but it is dependent on the sampling technique.

Adolescent↗
PubMedDate not supplied

Why am I scared of HPV?

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Carcinoma, Squamous Cell↗