Prevalence of HPV infection among females in the United States

Context  Human papillomavirus (HPV) infection is estimated to be the most common sexually transmitted infection. Baseline population prevalence data for HPV infection in the United States before widespread availability of a prophylactic HPV vaccine would be useful. Objective  To determine the prevalence of HPV among females in the United States. Design, Setting, and Participants  The National Health and Nutrition Examination Survey (NHANES) uses a representative sample of the US noninstitutionalized civilian population. Females aged 14 to 59 years who were interviewed at home for NHANES 2003-2004 were examined in a mobile examination center and provided a self-collected vaginal swab specimen. Swabs were analyzed for HPV DNA by L1 consensus polymerase chain reaction followed by type-specific hybridization. Demographic and sexual behavior information was obtained from all participants. Main Outcome Measures  HPV prevalence by polymerase chain reaction. Results  The overall HPV prevalence was 26.8% (95% confidence interval [CI], 23.3%-30.9%) among US females aged 14 to 59 years (n = 1921). HPV prevalence was 24.5% (95% CI, 19.6%-30.5%) among females aged 14 to 19 years, 44.8% (95% CI, 36.3%-55.3%) among women aged 20 to 24 years, 27.4% (95% CI, 21.9%-34.2%) among women aged 25 to 29 years, 27.5% (95% CI, 20.8%-36.4%) among women aged 30 to 39 years, 25.2% (95% CI, 19.7%-32.2%) among women aged 40 to 49 years, and 19.6% (95% CI, 14.3%-26.8%) among women aged 50 to 59 years. There was a statistically significant trend for increasing HPV prevalence with each year of age from 14 to 24 years (P<.001), followed by a gradual decline in prevalence through 59 years (P = .06). HPV vaccine types 6 and 11 (low-risk types) and 16 and 18 (high-risk types) were detected in 3.4% of female participants; HPV-6 was detected in 1.3% (95% CI, 0.8%-2.3%), HPV-11 in 0.1% (95% CI, 0.03%-0.3%), HPV-16 in 1.5% (95% CI, 0.9%-2.6%), and HPV-18 in 0.8% (95% CI, 0.4%-1.5%) of female participants. Independent risk factors for HPV detection were age, marital status, and increasing numbers of lifetime and recent sex partners. Conclusions  HPV is common among females in the United States. Our data indicate that the burden of prevalent HPV infection among females was greater than previous estimates and was highest among those aged 20 to 24 years. However, the prevalence of HPV vaccine types was relatively low.      

Screen-and-treat approaches for cervical cancer prevention in low-resource settings: a randomized controlled trial

Context  Non–cytology-based screen-and-treat approaches for cervical cancer prevention have been developed for low-resource settings, but few have directly addressed efficacy. Objective  To determine the safety and efficacy of 2 screen-and-treat approaches for cervical cancer prevention that were designed to be more resource-appropriate than conventional cytology-based screening programs. Design, Setting, and Patients  Randomized clinical trial of 6555 nonpregnant women, aged 35 to 65 years, recruited through community outreach and conducted between June 2000 and December 2002 at ambulatory women’s health clinics in Khayelitsha, South Africa. Interventions  All patients were screened using human papillomavirus (HPV) DNA testing and visual inspection with acetic acid (VIA). Women were subsequently randomized to 1 of 3 groups: cryotherapy if she had a positive HPV DNA test result; cryotherapy if she had a positive VIA test result; or to delayed evaluation. Main Outcome Measures  Biopsy-confirmed high-grade cervical cancer precursor lesions and cancer at 6 and 12 months in the HPV DNA and VIA groups compared with the delayed evaluation (control) group; complications after cryotherapy. Results  The prevalence of high-grade cervical intraepithelial neoplasia and cancer (CIN 2+) was significantly lower in the 2 screen-and-treat groups at 6 months after randomization than in the delayed evaluation group. At 6 months, CIN 2+ was diagnosed in 0.80% (95% confidence interval [CI], 0.40%-1.20%) of the women in the HPV DNA group and 2.23% (95% CI, 1.57%-2.89%) in the VIA group compared with 3.55% (95% CI, 2.71%-4.39%) in the delayed evaluation group (P<.001 and P = .02 for the HPV DNA and VIA groups, respectively). A subset of women underwent a second colposcopy 12 months after enrollment. At 12 months the cumulative detection of CIN 2+ among women in the HPV DNA group was 1.42% (95% CI, 0.88%-1.97%), 2.91% (95% CI, 2.12%-3.69%) in the VIA group, and 5.41% (95% CI, 4.32%-6.50%) in the delayed evaluation group. Although minor complaints, such as discharge and bleeding, were common after cryotherapy, major complications were rare. Conclusion  Both screen-and-treat approaches are safe and result in a lower prevalence of high-grade cervical cancer precursor lesions compared with delayed evaluation at both 6 and 12 months. Trial Registration  http://clinicaltrials.gov Identifier: NCT00233727.      

Incidence of cervical squamous intraepithelial lesions associated with HIV serostatus, CD4 cell counts, and human papillomavirus test results

Context  Recent cervical cancer screening guidelines state that the interval between screenings can be safely extended to 3 years in healthy women 30 years or older who have normal cytology results and have negative test results for oncogenic human papillomavirus (HPV) DNA. Objective  To determine the incidence of squamous intraepithelial lesions (SILs) in HIV-seropositive women with normal cytology results, by baseline HPV DNA results. Design, Setting, and Patients  Participants were HIV-seropositive (n = 855; mean age, 36 years) and HIV-seronegative (n = 343; mean age, 34 years) US women with normal baseline cervical cytology who were enrolled in the Women’s Interagency HIV Study (WIHS), a large, multi-institutional prospective cohort study. Since their recruitment during 1994-1995, WIHS participants have been followed up semi-annually with repeated Pap smears for a median of 7 years. Main Outcome Measure  The cumulative incidence of any SIL and high-grade SIL or cancer (HSIL+) was estimated according to baseline HPV DNA results, stratified by HIV serostatus and CD4 T-cell count. Results  Development of any SIL in women with negative HPV results (both oncogenic and nononcogenic) at 2 years was as follows: in HIV-seropositive women with CD4 counts less than 200/µL, 9% (95% CI, 1%-18%); with CD4 counts between 200/µL and 500/µL, 9% (95% CI, 4%-13%); and with CD4 counts greater than 500/µL, 4% (95% CI, 1%-7%). The CIs for these estimates overlapped with those for HIV-seronegative women with normal baseline cytology who were HPV-negative (3%; 95% CI, 1%-5%), indicating that at 2 years, there were no large absolute differences in the cumulative incidence of any SIL between groups. Furthermore, no HPV-negative participants in any group developed HSIL+ lesions within 3 years. Multivariate Cox models showed that on a relative scale, the incidence of any SIL among HIV-seropositive women with CD4 counts greater than 500/µL (hazard ratio [HR], 1.2; 95% CI, 0.5-3.0), but not those with CD4 counts less than or equal to 500/µL (HR, 2.9; 95% CI, 1.2-7.1), was similar to that in HIV-seronegative women. Conclusion  The similar low cumulative incidence of any SIL among HIV-seronegative and HIV-seropositive women with CD4 counts greater than 500/µL and who had normal cervical cytology and HPV-negative test results suggests that similar cervical cancer screening practices may be applicable to both groups, although this strategy warrants evaluation in an appropriate clinical trial.      

Feasibility of management of high-grade cervical lesions in a single visit: a randomized controlled trial

Context  The incidence of cervical cancer is higher among low-income and minority women who have never undergone a conventional Papanicolaou test or who do not follow up after testing. Screening has been shown to reduce cervical cancer incidence rates. Objectives  To determine the feasibility and acceptability of immediately treating women with severely abnormal Papanicolaou test results by using a single-visit cervical cancer screening and treatment program and to compare treatment rates and 12-month follow-up rates with those of women who received usual care. Design, Setting, and Participants  Randomized controlled trial conducted among 3521 women aged 18 years or older recruited between January 1999 and April 2002 at US community health centers located in predominantly Latino underserved areas. Interventions  Women randomized to usual care (n = 1805) were discharged immediately after examination. Women randomized to the single-visit group (n = 1716) remained at the clinic until the results of their conventional Papanicolaou test were available. Large loop electrosurgical excision procedure was performed in single-visit patients with either a diagnosis of a high-grade squamous intraepithelial lesion (HGSIL)/atypical glandular cells of undetermined significance (AGUS) or suspicion of carcinoma. All other patients with abnormal Papanicolaou test results were referred to abnormal cytology clinics or elected to receive follow-up care outside the study’s medical system. Main Outcome Measures  Treatment rates for HGSIL/AGUS at 6 months, follow-up rates at 6 months for lower-grade lesions, and 1-year follow-up rates for all patients. Results  The rate of abnormal Papanicolaou test results was 4.1%. One percent of results showed high-grade lesions. In the single-visit group, the mean visit time was 2.8 hours and the mean time for delivery and processing of the Papanicolaou tests was 66 minutes. Six months after randomization, 14 (88%) of 16 single-visit and 10 (53%) of 19 usual care patients with HGSIL/AGUS had completed treatment. Fifty percent in the single-visit program and 53% of usual care with less abnormal Papanicolaou tests completed treatment within 6 months. Overall, 36% in each group presented for a follow-up Papanicolaou test 1 year later. Women in the single-visit group with high-grade lesions (10/16; 63%) were significantly more likely to attend follow-up for Papanicolaou tests 12 months later than women with similar lesions in the usual care group (4/19; 21%). Conclusions  For cervical cancer screening, the single-visit program was feasible and the degree of acceptability was high in this underserved population. Single visit programs provide an opportunity to increase the rate of immediate treatment and follow-up of women with severely abnormal Papanicolaou test results. This strategy did not improve follow-up rates for women with less-abnormal results. Trial Registration  http://ClinicalTrials.govIdentifier: NCT00237562      

Evaluation of human papillomavirus testing in primary screening for cervical abnormalities: comparison of sensitivity,specificity, and frequency of referral

Context  Human papillomavirus (HPV) DNA testing of women having Papanicolaou (Pap) smears showing atypical squamous cells of undetermined significance (ASCUS) has clinical usefulness. Whether HPV DNA testing alone is useful in primary screening remains to be determined. Objective  To determine the accuracy of HPV DNA testing for detecting cervical intraepithelial neoplasia (CIN) grade 3 or cancer (the criterion standard). Design, Setting, and Participants  Between December 1997 and October 2000, 4075 women who attended Planned Parenthood clinics in Washington State were screened simultaneously using thin-layer Pap and HPV DNA testing by a polymerase chain reaction (PCR)–based method and by a liquid-based RNA-DNA hybridization capture with signal amplification assay (signal amplification). Women who were positive for high-risk HPV types, or had Pap results of ASCUS or higher, were considered to have positive screening test results and were referred for colposcopy and biopsy. Additionally, a random sample of women with negative screening test results was referred for colposcopy. Based on individual and combined thin-layer Pap, HPV PCR, and HPV signal amplification test results from the screening and the colposcopy visits, 7 colposcopy triage strategies were defined and evaluated. Main Outcome Measure  Sensitivity and specificity for detecting cervical lesions graded CIN 3 or higher for each of the 7 triage strategies. Results  The estimated prevalence of CIN 3 or higher was 3.2%. The sensitivity (95% confidence interval) of thin-layer Pap (with a result of ASCUS) for identifying women with CIN 3 or higher was only 61.3% (48.5%-70.9%) compared with 88.2% (78.9%-93.8%) for HPV testing by PCR and 90.8% (83.1%-95.8%) by signal amplification. Differences in specificities were also observed: 82.4% (81.8%-83.1%) for thin-layer Pap (with a result of ASCUS), 78.8% (77.9%-79.7%) for PCR, and 72.6% (69.4%-75.0%) for signal amplification. Compared with referral for colposcopy of all women with ASCUS or higher, signal amplification testing of women with ASCUS and referral of those with a positive result was about as sensitive (61.3% vs 60.3%, respectively) and significantly more specific (82.4% vs 88.9%, respectively). The strategy requiring repeat positive PCR tests on 2 visits had a sensitivity of 84.2% (75.3%-91.0%) and a specificity of 86.2% (85.1%-87.3%). All tests were more specific and less sensitive in older (30 years) vs younger women. Conclusions  Testing for HPV has higher sensitivity but lower specificity than thin-layer Pap screening. In some settings, particularly where screening intervals are long or haphazard, screening for HPV DNA may be a reasonable alternative to cytology-based screening of reproductive-age women.      

Serotypes of Chlamydia trachomatis and risk for development of cervical squamous cell carcinoma

Context  Human papillomavirus (HPV) infection has been established as a cause of cervical cancer. Epidemiologic studies suggest that Chlamydia trachomatis infection also confers increased risk for cervical squamous cell carcinoma (SCC). Whether this risk is serotype-specific is unknown. Objective  To study the association between exposure to different C trachomatis serotypes and subsequent development of cervical SCC. Design and Setting  Longitudinal, nested case-control study within a cohort of 530 000 women who provided samples to serum banks in Finland, Norway, and Sweden. The data files were linked to respective national cancer registries. Subjects  One hundred twenty-eight women who had developed invasive cervical SCC at least 12 months following serum donation. Each case had 3 matched controls. Main Outcome Measure  Risk for the development of cervical SCC by IgG antibodies to 10 different C trachomatis serotypes, adjusted for antibodies to HPV types 16, 18, and 33 and for serum cotinine levels. Results  Of specific C trachomatis serotypes, serotype G was most strongly associated with SCC (adjusted odds ratio [OR], 6.6; 95% confidence interval [CI], 1.6-27.0). Other serotypes associated with SCC were I (OR, 3.8; 95% CI, 1.3-11.0) and D (OR, 2.7; 95% CI, 1.3-5.6). Presence of serum IgG antibodies to more than 1 serotype increased the adjusted ORs for SCC (P<.001 for trend). Conclusions  Chlamydia trachomatis serotype G is most strongly associated with subsequent development of cervical SCC. Increasing numbers of exposures to different C trachomatis serotypes also increases risk. Our results strengthen the evidence that there is a link between past C trachomatis infection and cervical SCC.      

Medicine residents' understanding of the biostatistics and results in the medical literature

Context  Physicians depend on the medical literature to keep current with clinical information. Little is known about residents' ability to understand statistical methods or how to appropriately interpret research outcomes. Objective  To evaluate residents' understanding of biostatistics and interpretation of research results. Design, Setting, and Participants  Multiprogram cross-sectional survey of internal medicine residents. Main Outcome Measure  Percentage of questions correct on a biostatistics/study design multiple-choice knowledge test. Results  The survey was completed by 277 of 367 residents (75.5%) in 11 residency programs. The overall mean percentage correct on statistical knowledge and interpretation of results was 41.4% (95% confidence interval [CI], 39.7%-43.3%) vs 71.5% (95% CI, 57.5%-85.5%) for fellows and general medicine faculty with research training (P < .001). Higher scores in residents were associated with additional advanced degrees (50.0% [95% CI, 44.5%-55.5%] vs 40.1% [95% CI, 38.3%-42.0%]; P < .001); prior biostatistics training (45.2% [95% CI, 42.7%-47.8%] vs 37.9% [95% CI, 35.4%-40.3%]; P = .001); enrollment in a university-based training program (43.0% [95% CI, 41.0%-45.1%] vs 36.3% [95% CI, 32.6%-40.0%]; P = .002); and male sex (44.0% [95% CI, 41.4%-46.7%] vs 38.8% [95% CI, 36.4%-41.1%]; P = .004). On individual knowledge questions, 81.6% correctly interpreted a relative risk. Residents were less likely to know how to interpret an adjusted odds ratio from a multivariate regression analysis (37.4%) or the results of a Kaplan-Meier analysis (10.5%). Seventy-five percent indicated they did not understand all of the statistics they encountered in journal articles, but 95% felt it was important to understand these concepts to be an intelligent reader of the literature. Conclusions  Most residents in this study lacked the knowledge in biostatistics needed to interpret many of the results in published clinical research. Residency programs should include more effective biostatistics training in their curricula to successfully prepare residents for this important lifelong learning skill.      

Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among young women with preexisting infection: a randomized trial

Context  Viruslike particle human papillomavirus (HPV) vaccines were designed to prevent HPV infection and development of cervical precancers and cancer. Women with oncogenic HPV infections might consider vaccination as therapy. Objective  To determine whether vaccination against HPV types 16 and 18 increases the rate of viral clearance in women already infected with HPV. Design and Setting  Phase 3, masked, community-based randomized trial conducted in 2 provinces of Costa Rica. Participants  A total of 2189 women aged 18 to 25 years who were recruited between June 2004 and December 2005. Participants were positive for HPV DNA at enrollment, had at least 6 months of follow-up, and had follow-up HPV DNA results. Intervention  Participants were randomly assigned to receive 3 doses of a bivalent HPV-16/18 L1 protein viruslike particle AS04 candidate vaccine (n = 1088) or a control hepatitis A vaccine (n = 1101) over 6 months. Main Outcome Measures  Presence of HPV DNA was determined in cervical specimins by a molecular hybridization assay using chemiluminescence with HPV RNA probes and by polymerase chain reaction using SPF10 primers and a line probe assay detection system before vaccination and by polymerase chain reaction after vaccination. We compared rates of type-specific viral clearance using generalized estimating equations methods at the 6-month visit (after 2 doses) and 12-month visit (after 3 doses) in the 2 study groups. Results  There was no evidence of increased viral clearance at 6 or 12 months in the group who received HPV vaccine compared with the control group. Clearance rates for HPV-16/18 infections at 6 months were 33.4% (82/248) in the HPV vaccine group and 31.6% (95/298) in the control group (vaccine efficacy for viral clearance, 2.5%; 95% confidence interval, –9.8% to 13.5%). Human papillomavirus 16/18 clearance rates at 12 months were 48.8% (86/177) in the HPV vaccine group and 49.8% (110/220) in the control group (vaccine efficacy for viral clearance, –2.0%; 95% confidence interval, –24.3% to 16.3%). There was no evidence of a therapeutic effect for other oncogenic or nononcogenic HPV categories, among women receiving all vaccine doses, among women with single infections, or among women stratified by the following entry variables: HPV-16/18 serology, cytologic results, HPV DNA viral load, time since sexual debut, Chlamydia trachomatis or Neisseria gonorrhoeae infection, hormonal contraceptive use, or smoking. Conclusion  In women positive for HPV DNA, HPV-16/18 vaccination does not accelerate clearance of the virus and should not be used to treat prevalent infections. Trial Registration  clinicaltrials.gov Identifier: NCT00128661      

Prevalence of symptomatic pelvic floor disorders in US women

Ingrid Nygaard, MD, MS; Matthew D. Barber, MD, MHS; Kathryn L. Burgio, PhD; Kimberly Kenton, MD, MS; Susan Meikle, MD, MSPH; Joseph Schaffer, MD; Cathie Spino, DSc; William E. Whitehead, PhD; Jennifer Wu, MD, MPH; Debra J. Brody, MPH; for the Pelvic Floor Disorders Network

JAMA. 2008;300(11):1311-1316.

Context  Pelvic floor disorders (urinary incontinence, fecal incontinence, and pelvic organ prolapse) affect many women. No national prevalence estimates derived from the same population-based sample exists for multiple pelvic floor disorders in women in the United States.

Objective  To provide national prevalence estimates of symptomatic pelvic floor disorders in US women.

Design, Setting, and Participants  A cross-sectional analysis of 1961 nonpregnant women (20 years) who participated in the 2005-2006 National Health and Nutrition Examination Survey, a nationally representative survey of the US noninstitutionalized population. Women were interviewed in their homes and then underwent standardized physical examinations in a mobile examination center. Urinary incontinence (score of 3 on a validated incontinence severity index, constituting moderate to severe leakage), fecal incontinence (at least monthly leakage of solid, liquid, or mucous stool), and pelvic organ prolapse (seeing/feeling a bulge in or outside the vagina) symptoms were assessed.

Main Outcome Measures  Weighted prevalence estimates of urinary incontinence, fecal incontinence, and pelvic organ prolapse symptoms.

Results  The weighted prevalence of at least 1 pelvic floor disorder was 23.7% (95% confidence interval [CI], 21.2%-26.2%), with 15.7% of women (95% CI, 13.2%-18.2%) experiencing urinary incontinence, 9.0% of women (95% CI, 7.3%-10.7%) experiencing fecal incontinence, and 2.9% of women (95% CI, 2.1%-3.7%) experiencing pelvic organ prolapse. The proportion of women reporting at least 1 disorder increased incrementally with age, ranging from 9.7% (95% CI, 7.8%-11.7%) in women between ages 20 and 39 years to 49.7% (95% CI, 40.3%-59.1%) in those aged 80 years or older (P < .001), and parity (12.8% [95% CI, 9.0%-16.6%], 18.4% [95% CI, 12.9%-23.9%], 24.6% [95% CI, 19.5%-29.8%], and 32.4% [95% CI, 27.8%-37.1%] for 0, 1, 2, and 3 or more deliveries, respectively; P < .001). Overweight and obese women were more likely to report at least 1 pelvic floor disorder than normal weight women (26.3% [95% CI, 21.7%-30.9%], 30.4% [95% CI, 25.8%-35.0%], and 15.1% [95% CI, 11.6%-18.7%], respectively; P < .001). We detected no differences in prevalence by racial/ethnic group.

Conclusion  Pelvic floor disorders affect a substantial proportion of women and increase with age.

     

Effect of breast augmentation on the accuracy of mammography and cancer characteristics

Context  Breast augmentation is not associated with an increased risk of breast cancer; however, implants may interfere with the detection of breast cancer thereby delaying cancer diagnosis in women with augmentation. Objective  To determine whether mammography accuracy and tumor characteristics are different for women with and without augmentation. Design, Setting, and Participants  A prospective cohort of 137 women with augmentation and 685 women without augmentation diagnosed with breast cancer between January 1, 1995, and October 15, 2002, matched (1:5) by age, race/ethnicity, previous mammography screening, and mammography registry, and 10 533 women with augmentation and 974 915 women without augmentation and without breast cancer among 7 mammography registries in Denver, Colo; Lebanon, NH; Albuquerque, NM; Chapel Hill, NC; San Francisco, Calif; Seattle, Wash; and Burlington, Vt. Main Outcome Measures  Comparison between women with and without augmentation of mammography performance measures and cancer characteristics, including invasive carcinoma or ductal carcinoma in situ, tumor stage, nodal status, size, grade, and estrogen-receptor status. Results  Among asymptomatic women, the sensitivity of screening mammography based on the final assessment was lower in women with breast augmentation vs women without (45.0% [95% confidence interval {CI}, 29.3%-61.5%] vs 66.8% [95% CI, 60.4%-72.8%]; P = .008), and specificity was slightly higher in women with augmentation (97.7% [95% CI, 97.4%-98.0%] vs 96.7% [95% CI, 96.6%-96.7%]; P<.001). Among symptomatic women, both sensitivity and specificity were lower for women with augmentation compared with women without but these differences were not significant. Tumors were of similar stage, size, estrogen-receptor status, and nodal status but tended to be lower grade (P = .052) for women with breast augmentation vs without. Conclusions  Breast augmentation decreases the sensitivity of screening mammography among asymptomatic women but does not increase the false-positive rate. Despite the lower accuracy of mammography in women with augmentation, the prognostic characteristics of tumors are not influenced by augmentation.