Impact of the human papillomavirus status on the development of high-grade cervical intraepithelial neoplasia in women negative for intraepithelial lesions or malignancy at the baseline: A 9-year Swedish nested case-control follow-up study.

BACKGROUND: The causal relation between high-risk human papillomavirus (HPV) and cervical cancer and its precursor lesions has led to the use of sensitive HPV molecular tests for screening. This study examined the impact of the baseline HPV status on the future risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with cytology negative for intraepithelial lesions or malignancy (NILM). METHODS: This was a nested case-control study including women with NILM baseline cytology participating in the Swedish cervical screening program in 2005-2007. Ninety-six cases of CIN2+ and 5 age-matched controls per case were identified through the National Cervical Screening Registry by follow-up through 2014. Baseline liquid-based cytology samples were tested for HPV. Conditional logistic regression analysis was used to calculate odds ratios (ORs) with confidence intervals (CIs). RESULTS: The risk of future high-grade cervical intraepithelial neoplasia (CIN) was strongly associated with the baseline HPV status. For women younger than 30 years, HPV-16/18 showed a significant association with future risk for CIN2+ (OR, 9.44; 95% CI, 3.37-26.4). Other HPV types were not significantly associated with future CIN2+ in these younger women. For women 30 years old or older, both HPV-16/18 and other HPV subtypes conferred a significant risk. CONCLUSIONS: The presence of HPV-16/18 among women with NILM cytology is associated with an elevated future risk of high-grade CIN. HPV types other than HPV-16/18 seem to have a greater impact on women 30 years old or older than younger women. Women with NILM cytology and HPV-16/18 need specific follow-up management within screening.

Cost of Preventing, Managing, and Treating Human Papillomavirus (HPV)-Related Diseases in Sweden before the Introduction of Quadrivalent HPV Vaccination.

OBJECTIVE: Costs associated with HPV-related diseases such as cervical dysplasia, cervical cancer, and genital warts have not been evaluated in Sweden. These costs must be estimated in order to determine the potential savings if these diseases were eradicated and to assess the combined cost-effectiveness of HPV vaccination and cervical cancer screening. The present study aimed to estimate prevention, management, and treatment costs associated with cervical dysplasia, cervical cancer, and genital warts from a societal perspective in Sweden in 2009, 1 year before the quadrivalent HPV vaccination program was implemented. METHODS AND MATERIALS: Data from the Swedish cervical cancer screening program was used to calculate the costs associated with prevention (cytological cervical cancer screening), management (colposcopy and biopsy following inadequate/abnormal cytological results), and treatment of CIN. Swedish official statistics were used to estimate treatment costs associated with cervical cancer. Published epidemiological data were used to estimate the number of incident, recurrent, and persistent cases of genital warts; a clinical expert panel assessed management and treatment procedures. Estimated visits, procedures, and use of medications were used to calculate the annual cost associated with genital warts. RESULTS: From a societal perspective, total estimated costs associated with cervical cancer and genital warts in 2009 were €106.6 million, of which €81.4 million (76%) were direct medical costs. Costs associated with prevention, management, and treatment of CIN were €74 million; screening and management costs for women with normal and inadequate cytology alone accounted for 76% of this sum. The treatment costs associated with incident and prevalent cervical cancer and palliative care were €23 million. Estimated costs for incident, recurrent and persistent cases of genital warts were €9.8 million. CONCLUSION: Prevention, management, and treatment costs associated with cervical dysplasia, cervical cancer, and genital warts are substantial. Defining these costs is important for future cost-effectiveness analyses of the quadrivalent HPV vaccination program in Sweden.

Liquid-based cytology with HPV triage of low-grade cytological abnormalities versus conventional cytology in cervical cancer screening.

OBJECTIVE: Liquid-based cytology with supplementary human papillomavirus triage (LBC+HPV triage) of low-grade cytological abnormalities may improve the detection of cervical intraepithelial neoplasia (CIN) compared with conventional cytology. To investigate this subject, LBC+HPV triage and conventional cytology were alternated in a population-based screening setting. Cases with abnormal cytology were referred for colposcopy. METHODS: We compared the performance of LBC+HPV triage [n=4059] and conventional cytology [n=4261] in detecting CIN2 or worse [CIN2+] and CIN3 or worse [CIN3+]. We used logistic regression to assess CIN detection rates and abnormal cytology rates, which yielded unadjusted odds ratios (OR) and corresponding 95% confidence intervals (CI). We computed adjusted ORs from a multivariate logistic regression model that included potential confounders such as age, screening centre and time period. RESULTS: We found similar detection rates of CIN2+ by LBC+HPV triage and conventional cytology; the adjusted OR for the comparison of CIN detection rates was 0.87 (95% CI: 0.60-1.26) for CIN2+ and 1.00 (95% CI: 0.64-1.58) for CIN3+. We also found similar positive predictive values between methods. Thus, there was no advantage in using LBC+HPV triage as compared to conventional cytology in terms of sensitivity, specificity and positive and negative predictive value to detect histologically confirmed CIN2+ and CIN3+. CONCLUSIONS: LBC+HPV triage may lead to a reduction in unnecessary work-ups for women with abnormal cytological lesions who are negative for high-risk HPV. It is important to continuously monitor abnormal cytology rates, both when testing a new method, and after the new method has become routine.

Economic analysis of human papillomavirus triage, repeat cytology, and immediate colposcopy in management of women with minor cytological abnormalities in Sweden.

OBJECTIVE: To assess the cost-effectiveness of using human papillomavirus testing (HPV triage) in the management of women with minor cytological abnormalities in Sweden. DESIGN: An economic analysis based on a clinical trial, complemented with data from published meta-analyses on accuracy of HPV triage. The study takes perspective of the Swedish healthcare system. SETTING: The Swedish population-based cervical cancer screening program. METHODS: A decision analytic model was constructed to evaluate cost-effectiveness of HPV triage compared to repeat cytology and immediate colposcopy with biopsy, stratifying by index cytology (ASCUS = atypical squamous cells of undetermined significance, and LSIL = low-grade squamous intraepithelial lesion) and age (23-60 years, <30 years and ≥30 years). MAIN OUTCOME MEASURES: Costs, incremental cost, incremental effectiveness and incremental cost per additional high-grade lesion (CIN2+) detected. RESULTS: For women with ASCUS ≥30 years, HPV triage is the least costly alternative, whereas immediate colposcopy with biopsy provides the most effective option at an incremental cost-effectiveness ratio (ICER) of SEK 2,056 per additional case of CIN2+ detected. For LSIL (all age groups) and ASCUS (23-60 years and <30 years), HPV triage is dominated by immediate colposcopy and biopsy. Model results were sensitive to HPV test cost changes. CONCLUSION: With improved HPV testing techniques at lower costs, HPV triage can become a cost-effective alternative for follow-up of minor cytological abnormalities. Today, immediate colposcopy with biopsy is a cost-effective alternative compared to HPV triage and repeat cytology.