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Results of cytology and high-risk human papillomavirus testing in females with cervical adenocarcinoma in situ.

ABSTRACT: The incidence rates of cervical adenocarcinoma have been increasing over the last two decades, contrary to those of squamous cell carcinoma. This trend is particularly evident among females aged <40 years and has occurred despite extensive cytology-based screening programs. The aim of the present retrospective database study was to investigate adenocarcinoma in situ (AIS) with respect to previous cytological results, high-risk (HR) human papillomavirus (HPV) infections and histological results from AIS-adjacent squamous mucosa. Databases were used to identify 32 female patients with AIS treated for various conditions between 2009 and 2012 at the Department of Gynecology, Uppsala University Hospital (Uppsala, Sweden) and previous cytological, HPV and histological results. Of the individuals in the study, 64.3% had a previously recorded cytological result showing squamous cell abnormalities; five had glandular cell abnormalities (18%) and two had AIS (7.1%). Among the patients with available HPV results, 95% were HR-HPV-positive; HPV18/45 predominated (77%), followed by HPV16 (27%). The patients with multiple HPV infections were aged ?32 years, while patients aged ?38 years were only infected with HPV18/45. All but three patients had cervical intraepithelial neoplasia (CIN) in the AIS-adjacent squamous mucosa, 79% of which was CIN2 or worse. The present retrospective database study suggests that AIS is detected at screening mainly due to simultaneous squamous precursor lesions and that HPV18/45 infection is an increasing cofactor for AIS in older patients. HPV analyses of glandular precursor lesions aid in the identification of female individuals at risk of progression to invasive disease, and thus have a favorable effect on adenocarcinoma prevention, together with vaccination.

SUBMITTER: Andersson S

PROVIDER: S-EPMC3742506 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Results of cytology and high-risk human papillomavirus testing in females with cervical adenocarcinoma <i>in situ.</i>

Andersson Sonia S Mints Miriam M Wilander Erik E

Oncology letters 20130515 1

The incidence rates of cervical adenocarcinoma have been increasing over the last two decades, contrary to those of squamous cell carcinoma. This trend is particularly evident among females aged <40 years and has occurred despite extensive cytology-based screening programs. The aim of the present retrospective database study was to investigate adenocarcinoma <i>in situ</i> (AIS) with respect to previous cytological results, high-risk (HR) human papillomavirus (HPV) infections and histological re ...[more]

PMID: 23946807

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Project description:ObjectiveTo provide the first report on the main outcomes from the prevalence and incidence rounds of a large pilot of routine primary high risk human papillomavirus (hrHPV) testing in England, compared with contemporaneous primary liquid based cytology screening.DesignObservational study.SettingThe English Cervical Screening Programme.Participants578 547 women undergoing cervical screening in primary care between May 2013 and December 2014, with follow-up until May 2017; 183 970 (32%) were screened with hrHPV testing.InterventionsRoutine cervical screening with hrHPV testing with liquid based cytology triage and two early recalls for women who were hrHPV positive and cytology negative, following the national screening age and interval recommendations.Main outcome measuresFrequency of referral for a colposcopy; adherence to early recall; and relative detection of cervical intraepithelial neoplasia grade 2 or worse from hrHPV testing compared with liquid based cytology in two consecutive screening rounds.ResultsBaseline hrHPV testing and early recall required approximately 80% more colposcopies, (adjusted odds ratio 1.77, 95% confidence interval 1.73 to 1.82), but detected substantially more cervical intraepithelial neoplasia than liquid based cytology (1.49 for cervical intraepithelial neoplasia grade 2 or worse, 1.43 to 1.55; 1.44 for cervical intraepithelial neoplasia grade 3 or worse, 1.36 to 1.51) and for cervical cancer (1.27, 0.99 to 1.63). Attendance at early recall and colposcopy referral were 80% and 95%, respectively. At the incidence screen, the 33 506 women screened with hrHPV testing had substantially less cervical intraepithelial neoplasia grade 3 or worse than the 77 017 women screened with liquid based cytology (0.14, 0.09 to 0.23).ConclusionsIn England, routine primary hrHPV screening increased the detection of cervical intraepithelial neoplasia grade 3 or worse and cervical cancer by approximately 40% and 30%, respectively, compared with liquid based cytology. The very low incidence of cervical intraepithelial neoplasia grade 3 or worse after three years supports extending the screening interval.

Project description:BACKGROUND: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. METHODS: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. FINDINGS: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. INTERPRETATION: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. FUNDING:Intramural Research Program of the US National Cancer Institute/NIH/DHHS, and the American Cancer Society.

Project description:ObjectiveHigh-risk human papillomavirus (HrHPV)-positive women detected by self-sampling require an extra visit at the general practitioner for additional cytology testing, but the loss to follow up within this triage is substantial. The aim of this study was to evaluate the clinical utility of reflex cytology on hrHPV-positive self-samples for immediate stratification of women who need referral for colposcopy.DesignA prospective cohort study.SettingTwo Dutch cervical cancer-screening laboratories.Population1014 screenees who tested hrHPV-positive on self-samples between 1 December 2018 and 1 August 2019.MethodsSelf-samples were directly used for cytological analysis. Cytological and histological outcomes during follow up were obtained from the Dutch Pathology Registry (PALGA).Main outcome measuresTest performance of reflex cytology on self-samples was determined for different thresholds and compared with physician-taken cytology and histological outcomes.ResultsReflex cytology on self-samples for detecting abnormal cytology showed a sensitivity of 26.4% (95% CI 21.8-31.3) and specificity of 90.5% (95% CI 87.7-92.8). Of all ≥CIN2 cases, 29.4% (95% CI 22.5-37.1) were detected with reflex cytology on self-samples. The positive predictive value for detection of ≥CIN2 was higher with cytology on self-collected samples than on physician-collected samples. Of women who were lost to follow up, 12.9% were found to have abnormal cytology on their self-sampled material.ConclusionCytology testing is achievable on hrHPV-positive self-samples, could decrease the loss to follow up in screening and is easily implementable in the current clinical practice. Of all hrHPV-positive women with abnormal cytology on additional physician-collected samples, 26.4% could have been directly referred for colposcopy if triage with reflex cytology on self-sampled material had been performed.Tweetable abstractReflex cytology for triage of hrHPV+ self-samples is of added value for direct referral of women for colposcopy.

Dataset Information

Results of cytology and high-risk human papillomavirus testing in females with cervical adenocarcinoma in situ.

Publications

Results of cytology and high-risk human papillomavirus testing in females with cervical adenocarcinoma <i>in situ.</i>

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