Article

Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a population-based study in routine clinical practice

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD 20882, USA.
The Lancet Oncology (Impact Factor: 24.73). 07/2011; 12(7):663-72. DOI: 10.1016/S1470-2045(11)70145-0
Source: PubMed

ABSTRACT Concurrent testing for human papillomavirus (HPV) and cervical cytology (co-testing) is an approved alternative to cytology alone in women aged 30 years and older. We aimed to assess the safety in routine clinical practice of 3-year screening intervals for women testing negative for HPV with normal cytology and to assess if co-testing can identify women at high risk of cervical cancer or cervical intraepithelial neoplasia grade 3 (CIN3) or worse over 5 years.
We assessed the 5-year cumulative incidence, starting in 2003-05, of cervical cancer and CIN3 or worse for 331,818 women aged 30 years and older who enrolled in co-testing at Kaiser Permanente Northern California (Berkeley, CA, USA) and had adequate enrolment co-test results. Follow-up continued until Dec 31, 2009. We defined cumulative incidence to include prevalence at enrolment and incidence after enrolment. Prevalence at enrolment was defined as the ratio of women diagnosed with each outcome on the biopsy visit immediately after their enrolment screening visit to the total enrolled women. At screening visits only HPV test and Pap smear samples were collected, and at biopsy visits colposcopically directed biopsies were taken. To estimate post-enrolment incidence, we used Weibull survival models.
In 315,061 women negative by HPV testing, the 5-year cumulative incidence of cancer was 3.8 per 100,000 women per year, slightly higher than for the 306,969 who were both negative by HPV and Pap testing (3.2 per 100,000), and half the cancer risk of the 319,177 who were negative by Pap testing (7.5 per 100,000). 313,465 (99.5%) women negative by HPV testing had either normal cytology or equivocal abnormalities. Abnormal cytology greatly increased cumulative incidence of CIN3 or worse over 5 years for the 16,757 positive by HPV testing (12.1%vs 5.9%; p<0.0001). By contrast, although statistically significant, abnormal cytology did not increase 5-year risk of CIN3 or worse for women negative by HPV testing to a substantial level (0.86%vs 0.16%; p=0.004). 12,208 (73%) of the women positive by HPV testing had no cytological abnormality, and these women had 258 (35%) of 747 CIN3 or adenocarcinoma in situ, [corrected] 25 (29%) of 87 cancers, and 17 (63%) of 27 adenocarcinomas.
For women aged 30 years and older in routine clinical practice who are negative by co-testing (both HPV and cytology), 3-year screening intervals were safe because a single negative test for HPV was sufficient to reassure against cervical cancer over 5 years. Incorporating HPV testing with cytology also resulted in earlier identification of women at high risk of cervical cancer, especially adenocarcinoma. Testing for HPV without adjunctive cytology might be sufficiently sensitive for primary screening for cervical cancer.
Intramural Research Program of the US National Cancer Institute/NIH/DHHS, and the American Cancer Society.

1 Follower
 · 
137 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: Combining HPV and Pap screening achieves very good risk stratification and sensitive detection of CIN3 and cancer (CIN3+), but poorer specificity, and may result in an increased risk of glandular and new lesions during follow-up. We examined if this phenomenon may compromise the accuracy of colposcopy. METHODS: As part of a primary HPV screening pilot project comprising 19,624 participants aged over 30years, the failure rate to detect CIN3 at first visit was measured over a five-year period to assess the quality of colposcopy as an overall management concept. Management relied on excisional biopsies in all HSIL cytology or major findings on colposcopy, endocervical assessment in type 3 transformation zones (TZ) and guided biopsies in type 1 or 2 TZ. RESULTS: Of 667 women referred for colposcopy because of atypical Pap smears and/or HPV persistency, 171 were diagnosed with CIN3+. All 18 cancers and 140/153 CIN3 cases were diagnosed at the first visit. Of 13 CIN3 observed during follow-up, five were classified as new cases, five as definite and three as probably colposcopy failures, giving a failure rate of 4.7% (8/171). Only three failures were related to false-negative punch biopsies while five occurred because of false-negative endocervical assessment in type 3 TZ. CONCLUSIONS: Colposcopy management following defined pathways was safe in this HPV screening programme with an acceptable failure rate. Further improvements may depend on developing better methods for endocervical assessment rather than for ectocervical biopsies.
    Gynecologic Oncology 10/2012; DOI:10.1016/j.ygyno.2012.10.017 · 3.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Many studies have examined the short-term value of high-risk human papillomavirus (hrHPV) testing in predicting cumulative risk of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+). This study focuses on long-term CIN3+ risk after initial wait and see policy. A total of 342 women with abnormal cytology of borderline/mild dyskaryosis (BMD) or worse (>BMD), included between 1990 and 1992, were followed-up by cytology and hrHPV testing until 1996 and monitored by cytology thereafter. Primary endpoint was cumulative CIN3+ risk by December 2009. Women with BMD had a 5-year CIN3+ risk of 22.5% (95% confidence interval (CI) 17.0-29.1) and of 0.7% (0.1-4.5) in the subsequent 5 years. High-risk human papillomavirus-negative women with BMD had a 5-year risk of <0.01% (95% CI 0.0-5.1) and of <0.01% (0.0-5.7) in the following 5 years, while for hrHPV-positive women these risks were 37.5% (29.0-46.9) and 1.6% (0.2-9.5), respectively. Women with >BMD had a 5-year risk of 45.1% (36.4-54.1) and of 3.5% (0.9-12.2) in the subsequent 5 years. High-risk human papillomavirus-negative women with >BMD had a 5-year risk of 7.3% (2.0-23.6) and hrHPV-positive women of 56.6% (46.4-66.3). Women with BMD have an elevated CIN3+ risk for 5 years only; afterwards their risk is similar to the general population. High-risk human papillomavirus-negative women with BMD may return to regular screening directly. All other women with BMD should be referred for additional testing and/or colposcopy.
    British Journal of Cancer 02/2012; 106(5):817-25. DOI:10.1038/bjc.2012.5 · 4.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Different Human Papilloma Virus (HPV) tests are currently used. An integrated comparison of the Amplicor, Cobas4800, PreTect HPV-Proofer and APTIMA HPV tests has not been done. We compared the high-risk HPV detection power of these HPV tests in 528 consecutive population-based follow-up Liquid-Based Cytology samples (LBC) after ASCUS/LSIL index cytology. Their sensitivity and specificity to detect HPV in LBC, their predictive values of histopathologic CIN2-3 in follow-up punch biopsies and CIN2-3 regression in the subsequent cones was assessed. The HPV subtypes detected by the Linear Array genotyping-test (LA), PreTect HPV-Proofer and Cobas4800 were also compared. The follow-up histopathology was consensus expert-reviewed and Ki67/p16-supported. The predictive values of the HPV results in LBC by the different tests for presence of CIN2-3 in follow-up biopsies, and regression in subsequent cones, was assessed. Amplicor, Cobas4800 and APTIMA show good agreement for HPV-positivity/negativity. PreTect HPV-Proofer has many discrepancies versus any of the other methods. The sensitivities for Amplicor, Cobas4800 and APTIMA to detect CIN2-3 were very high (96-100%), but rather low for PreTect HPV-Proofer (53%). Specificity in case of CIN1 or less in follow-up biopsies of Amplicor and Cobas4800 is lower than APTIMA and highest for PreTect HPV-Proofer. HPV subtyping by LA agreed in 90% with Cobas4800 but 70% with PreTect HPV-Proofer. The Amplicor, Cobas4800 and APTIMA give comparable results but PreTect HPV-Proofer differs from the other tests, with low sensitivity but higher specificity. None of the methods predicted regression of CIN2-3.
    Gynecologic Oncology 08/2011; 123(2):278-83. DOI:10.1016/j.ygyno.2011.07.024 · 3.69 Impact Factor

Preview

Download
11 Downloads
Available from