High-Risk Types of Human Papilloma Virus DNA Testing in Women with False Negative Cytology.

OBJECTIVE: To determine whether high-risk types of human papilloma virus (hrHPV) DNA testing is reliable for selection patients in need of further investigation with colposcopy in women with increased risk of high-grade cervical lesions as a result of false negative cytology. The secondary objective was to compare the sensitivity of hrHPV testing on self-collected versus physician-collected samples for the detection of histological high-grade cervical intraepithelial neoplasia (CIN2+). METHODS: Sixty-three patients identified with a missed abnormality following the re-evaluation of benign cervical cytology were included. A patient-collected and a physician-collected sample for HPV, colposcopy and cervical specimen collection for histology and cytology were performed. RESULTS: The sensitivity of hrHPV testing of physician-collected samples for CIN2+ was 100% (95% CI 82.7-100), and the negative predictive value (NPV) was 100% (95% CI 93.3-100). The sensitivity of the self-sampling device to identify CIN2+ was 84.6% (95% CI 59.1-96.7), and the NPV was 94.4% (95% CI 83.4-98.8). The differences in the sensitivity and NPV between the 2 methods were non-significant. The agreement between the 2 methods regarding the HPV results was good, with a kappa value of 0.74 (95% CI 0.57-0.91). CONCLUSION: The current findings indicate that physician-collected samples for hrHPV DNA testing may be used as triage for the colposcopy of women with false negative cytology.

Screening and cervical cancer cure: population based cohort study.

OBJECTIVE: To determine whether detection of invasive cervical cancer by screening results in better prognosis or merely increases the lead time until death. DESIGN: Nationwide population based cohort study. SETTING: Sweden. PARTICIPANTS: All 1230 women with cervical cancer diagnosed during 1999-2001 in Sweden prospectively followed up for an average of 8.5 years. MAIN OUTCOME MEASURES: Cure proportions and five year relative survival ratios, stratified by screening history, mode of detection, age, histopathological type, and FIGO (International Federation of Gynecology and Obstetrics) stage. RESULTS: In the screening ages, the cure proportion for women with screen detected invasive cancer was 92% (95% confidence interval 75% to 98%) and for symptomatic women was 66% (62% to 70%), a statistically significant difference in cure of 26% (16% to 36%). Among symptomatic women, the cure proportion was significantly higher for those who had been screened according to recommendations (interval cancers) than among those overdue for screening: difference in cure 14% (95% confidence interval 6% to 23%). Cure proportions were similar for all histopathological types except small cell carcinomas and were closely related to FIGO stage. A significantly higher cure proportion for screen detected cancers remained after adjustment for stage at diagnosis (difference 15%, 7% to 22%). CONCLUSIONS: Screening is associated with improved cure of cervical cancer. Confounding cannot be ruled out, but the effect was not attributable to lead time bias and was larger than what is reflected by down-staging. Evaluations of screening programmes should consider the assessment of cure proportions.

Risk of invasive cervical cancer in relation to clinical investigation and treatment after abnormal cytology: a population-based case-control study.

A substantial proportion of women with cervical cancer that have participated in cervical screening have a history of an abnormal cytology result. Our objective was to assess the impact of histological investigation and treatment of women with abnormal cytology on the subsequent risk of invasive cervical cancer. All invasive cervical cancer cases in Sweden 1999-2001 and five population-based control women per case were investigated. Clinical investigations and treatment were analysed in case women (N = 143) and control women (N = 176) below 67 with abnormal cytology results 0.5-6.5 years before the cases' diagnosis. Cervical cancer risk in relation to investigation [histology or not, punch biopsy, cervical curettage or cone/large loop excision of the transformation zone (LLETZ)], and treatment (treatment or not, excisional or ablative) was estimated as odds ratios (ORs) using logistic regression. Absence of histological assessment was associated with increased cancer risk, both after low-grade [OR 2.37; 95% confidence intervals (CI): 1.27-4.43] and high-grade squamous atypia (8.26; 2.37-28.8). Among women with histology, absence of treatment was associated with increased cancer risk (3.68; 1.53-8.84), also when biopsy showed low-grade atypia or normal findings (3.57; 1.18-10.8). Ablative therapy associated with increased risk compared with excisional (3.82; 1.01-14.4), and laser conisation associated with decreased risk compared with LLETZ (0.06; 0.01-0.36). In conclusion, low-grade as well as high-grade squamous atypical cytology results may warrant histological investigation, treatment reduced cancer risk even when histology was negative or showed low-grade atypia indicating a need for improvements in the diagnosis of high-grade lesions, and laser conisation was the most effective treatment.

Risk of invasive cervical cancer in relation to management of abnormal Pap smear results.

OBJECTIVE: We sought to evaluate the management of women with abnormal cytology in terms of subsequent risk of invasive cervical cancer. STUDY DESIGN: The screening histories of all invasive cervical cancer cases diagnosed in Sweden 1999-2001 and of 5 population-based controls per case were reviewed. In all, 159 patients and 258 control subjects aged < 67 years had an abnormal smear result 0.5-6.5 years prior to cancer diagnosis. The cervical cancer risk was estimated in relation to management by calculating odds ratios. RESULTS: Histologic assessment of low-grade squamous abnormalities strongly reduced the risk compared to repeated cytology (odds ratio, 0.46; 95% confidence interval, 0.24-0.89). Delaying histologic assessment was also associated with a higher risk (odds ratio, 5.65; 95% confidence interval, 1.39-23.05). After high-grade squamous atypia, absence of any cytologic or histologic specimen was a major determinant of cancer risk (odds ratio, 12.52; 95% confidence interval, 1.42-infinitive). CONCLUSION: For adequate protection against invasive cervical cancer, further assessment with histology must be recommended also for women with low-grade squamous abnormalities.

Screening-preventable cervical cancer risks: evidence from a nationwide audit in Sweden.

BACKGROUND: The effectiveness of cervical cancer screening programs differs widely in different populations. The reasons for these differences are unclear. Routine and comprehensive audits have been proposed as an ethically required component of screening. We performed a nationwide audit of the effectiveness of the Swedish cervical cancer screening program. METHODS: We identified all invasive cervical cancer cases that were diagnosed in Sweden from January 1, 1999, through December 31, 2001, and had been reported to the Swedish Cancer Registry (n = 1230 cases). We verified the diagnoses by histopathologic rereview and matched each case subject to five (population-based) age-matched control subjects who were identified from the National Population Register. The Pap smear screening histories for case and control subjects were reviewed for a 6-year period using the National Cervical Cancer Screening Register, which contains data on essentially all relevant cytological and histological diagnoses in Sweden. Odds ratios (ORs), and their 95% confidence intervals (CIs), of cervical cancer according to screening history were calculated in conditional logistic regression models. All statistical tests were two-sided. RESULTS: Women who had not had a Pap smear within the recommended screening interval had higher risk of cervical cancer than women who had been screened (OR = 2.52, 95% CI = 2.19 to 2.91). This risk was similarly increased for all age groups (P(homogeneity) = .96). The risk for non-squamous cell cervical cancers (OR = 1.59, 95% CI = 1.20 to 2.11) was also increased. Women who had not had a Pap smear within the recommended screening interval had a particularly high risk of advanced cancers (OR = 4.82, 95% CI = 3.61 to 6.44). Among women who had been screened within the recommended interval, those with abnormal Pap smears had a higher risk of cervical cancer than those with normal smears (OR = 7.55, 95% CI = 5.88 to 9.69) and constituted 11.5% of all women with cervical cancer. CONCLUSIONS: Nonadherence to screening intervals was the major reason for cervical cancer morbidity. The screening program was equally effective for women of all ages and was also effective against non-squamous cancers.

A randomized trial of basing treatment on human papillomavirus and/or cytology results in low-grade cervical lesion triage.

OBJECTIVE: This study was undertaken to compare management algorithms that base treatment with loop electrosurgical excision procedure on human papillomavirus and/or repeat Papanicolaou test smear results. STUDY DESIGN: A randomized trial that referred 674 women with either atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions cytology results, detected in organized screening to treatment either (1) if they were positive in a repeat Papanicolaou test smear and/or a human papillomavirus test or (2) if they were positive in the repeat Papanicolaou test smear test only. Women who tested positive were treated, regardless of colposcopic findings. RESULTS: There were 208 of 337 (62%) women who were treated in the human papillomavirus /Papanicolaou test smear group (187/337 because of HPV positivity) and 138 of 337 (41%) in the Papanicolaou test smear only group. Histopathologically diagnosed cervical intraepithelial neoplasia grade 2 or worse was found among 112 of 337 (33.2%) women in the human papillomavirus/Papanicolaou test smear group compared with 85 of 337 (25.2%) women in the Papanicolaou test smear only group (P < .05). Twenty-one women with cervical intraepithelial neoplasia 2+ had normal colposcopy. CONCLUSION: For adequate cervical intraepithelial neoplasia 2+ sensitivity, the decision to use loop electrosurgical excision procedure needs to be based on human papillomavirus testing results and should not exclude women with normal colposcopy.