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1.  Screening for Cervical Cancer: A Modeling Study for the U.S. Preventive Services Task Force 
Objective
This study addresses three questions posed by the United States Preventive Services Task Force (USPSTF): 1) At what age should screening for cervical cancer begin; 2) At what age should screening for cervical cancer end; and 3) How do the benefits and potential harms of screening strategies that use human papillomavirus (HPV) DNA testing in conjunction with cytology (co-testing) compare to those strategies that use cytology only?
Methods
A Markov model was updated and used to quantify clinical outcomes (i.e. colposcopies, cancers, life expectancy) associated with different screening strategies.
Results
Screening in the teenage years is associated with a high number of colposcopies small differences in cancers detected and, as a result, small gains in life expectancy. Screening women beginning in the early 20s provides a reasonable balance of the harms and benefits of screening. Among women who have been screened according to the current recommendations for cervical cancer (beginning at age 21, and conducted every 3 years with cytology), screening beyond age 65 is associated with small additional gains in life expectancy but large increases in colposcopies. In terms of co-testing, a strategy of cytology only conducted every 3 years, followed by co-testing conducted every 5 years (for women aged 30+ years) is associated with fewer colposcopies and greater gains in life-expectancy compared to screening with cytology-only conducted every 3 years.
Conclusions
The results of this modeling study support current USPSTF recommendations for cervical cancer screening.
doi:10.1097/LGT.0b013e3182616241
PMCID: PMC3608928  PMID: 23519288
cervical cancer screening; colposcopies; modeling
2.  Modeling Preventative Strategies against HPV-Related Disease in Developed Countries 
Vaccine  2012;30(0 5):F157-F167.
Over the last five years, prophylactic vaccination against Human Papillomavirus (HPV) in pre-adolescent females has been introduced in most developed countries, supported by modeled evaluations which have almost universally found vaccination of pre-adolescent females to be cost-effective. Studies to date suggest that vaccination of pre-adolescent males may also be cost-effective at a cost per vaccinated individual ~US$400–500 if vaccination coverage in females cannot be increased above ~50%; but if it is possible, increasing coverage in females appears to be a better return on investment. Comparative evaluation of the quadrivalent (HPV16,18,6,11) and bivalent (HPV16,18) vaccines centers around the potential tradeoff between protection against anogenital warts and vaccine-specific levels of cross-protection against infections not targeted by the vaccines. Future evaluations will also need to consider the cost-effectiveness of a next generation nonavalent vaccine designed to protect against ~90% of cervical cancers. The timing of the effect of vaccination on cervical screening programs will be country-specific and will depend on vaccination catch-up age range and coverage and the age at which screening starts. Initial evaluations suggest that if screening remains unchanged it will be less cost-effective in vaccinated compared to unvaccinated women but, in the context of current vaccines, will remain an important prevention method. Comprehensive evaluation of new approaches to screening will need to consider the population-level effects of vaccination over time. New screening strategies of particular interest include delaying the start age of screening, increasing the screening interval and switching to primary HPV screening. Future evaluations of screening will also need to focus on the effects of disparities in screening and vaccination uptake, the potential effects of vaccination on screening participation, and the effects of imperfect compliance with screening recommendations.
doi:10.1016/j.vaccine.2012.06.091
PMCID: PMC3783354  PMID: 23199959
HPV; Intraepithelial neoplasia; Uterine cervical neoplasms; Vulvar; vaginal; anal; oral cavity and oropharyngeal cancer; Anogenital warts; Recurrent Respiratory Papillomatoses; Vaccines; Mathematical models; Cervical cancer screening; Cost-effectiveness analysis; Developed countries
3.  Accuracy and Cost-Effectiveness of Cervical Cancer Screening by High-Risk HPV DNA Testing of Self-Collected Vaginal Samples 
Objective
Estimate the accuracy and cost-effectiveness of cervical cancer screening strategies based on high-risk HPV DNA testing of self-collected vaginal samples.
Materials and Methods
A subset of 1,665 women (18-50 years of age) participating in a cervical cancer screening study were screened by liquid-based cytology and by high-risk HPV DNA testing of both self-collected vaginal swab samples and clinician-collected cervical samples. Women with positive/abnormal screening test results and a subset of women with negative screening test results were triaged to colposcopy. Based on individual and combined test results, five screening strategies were defined. Estimates of sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or worse were calculated and a Markov model was used to estimate the incremental cost-effectiveness ratios (ICERs) for each strategy.
Results
Compared to cytology-based screening, high-risk HPV DNA testing of self-collected vaginal samples was more sensitive (68%, 95%CI=58%-78% versus 85%, 95%CI=76%-94%) but less specific (89%, 95%CI=86%-91% versus 73%, 95%CI=67%-79%). A strategy of high-risk HPV DNA testing of self-collected vaginal samples followed by cytology triage of HPV positive women, was comparably sensitive (75%, 95%CI=64%-86%) and specific (88%, 95%CI=85%-92%) to cytology-based screening. In-home self-collection for high-risk HPV DNA detection followed by in-clinic cytology triage had a slightly lower lifetime cost and a slightly higher quality-adjusted life expectancy than did cytology-based screening (ICER of triennial screening compared to no screening was $9,871/QALY and $12,878/QALY, respectively).
Conclusions
Triennial screening by high-risk HPV DNA testing of in-home, self-collected vaginal samples followed by in-clinic cytology triage was cost-effective.
doi:10.1097/LGT.0b013e3181cd6d36
PMCID: PMC2898894  PMID: 20592553
cervical cancer; screening; hpv; self-collect; cost-effectiveness
4.  Depot-medroxyprogesterone Acetate and Combined Oral Contraceptive Use and Cervical Neoplasia among Women with Oncogenic Human Papillomavirus Infection 
Objective
Examine the relationship of depot-medroxyprogesterone acetate (DMPA) and combined oral contraceptive (COC) use with cervical intraepithelial neoplasia (CIN).
Study Design
Two case-control studies of women who presented for gynecological care and underwent cytologic and human papillomavirus (HPV) testing were performed. The first included oncogenic HPV-positive women grouped based on histology: negative(n=152), CIN1(n=133), and ≥CIN2-3(n=173). For the second, two groups were identified: negative HPV/negative histology(n=107) and positive oncogenic HPV/negative histology(n=152).
Results
Among oncogenic HPV-positive women, DMPA use was inversely associated with ≥CIN2-3 (adjusted odds ratio[ORadj]=0.4;95% confidence interval[CI]=0.2–1.1) and CIN1 (ORadj=0.1;95% CI=0.01–0.6); COC use was not associated with either. Among histologically negative women, DMPA use was associated with oncogenic HPV (ORadj=4.7;95% CI=1.4–15.8).
Conclusions
Among women with oncogenic HPV, hormonal contraceptive use was not associated with an increased risk of ≥CIN2-3. Longer-term DMPA use may attenuate the colposcopic and histologic features of CIN as women reporting such use were more likely than others to have cervical oncogenic HPV without evidence of CIN.
doi:10.1016/j.ajog.2009.01.030
PMCID: PMC2713031  PMID: 19375566
CIN; hormonal contraception; DMPA; Oncogenic HPV infection
5.  Human papillomavirus testing with Pap triage for cervical cancer prevention in Canada: a cost-effectiveness analysis 
BMC Medicine  2009;7:69.
Background
Recently published results from a large randomized trial (Canadian Cervical Cancer Screening Trial study group) suggest that human papillomavirus testing followed by Pap smear-based triage for human papillomavirus positive women may be an effective way to screen women for cervical cancer. We determined the potential cost-effectiveness of including human papillomavirus tests for cervical cancer screening for Canada and three provinces: Alberta, Newfoundland and Ontario.
Methods
We developed four Markov decision models using data from relevant Canadian and provincial studies and databases. The models were used to determine the number of false positive test results, cancers, lifetime costs and life-expectancy for 27 different screening strategies that varied by age to begin screening (18 or 25 years), screening interval (one, two, three, or five years) and whether the currently recommended strategy (screening every year from age 18 until 21 and then every three years afterwards with conventional Paps) was conducted prior to age 25. Strategies were compared using incremental cost-effectiveness ratios.
Results
Screening strategies beginning at age 18 were associated with a substantial increase in the number of false-positive test results but only small differences in the number of cancers compared to the same strategy conducted beginning at age 25. Strategies of human papillomavirus testing first, followed by triage with Pap smears were associated with lower costs and greater increases in life-expectancy than the currently recommended screening strategy in Canada.
Conclusion
A strategy of human papillomavirus testing beginning at age 25, with Pap triage for women with positive human papillomavirus results may be more effective at reducing cervical cancer at a lower cost than the current recommended strategy for screening in Canada.
doi:10.1186/1741-7015-7-69
PMCID: PMC2780455  PMID: 19900264
6.  Adding a quadrivalent human papillomavirus vaccine to the UK cervical cancer screening programme: A cost-effectiveness analysis 
Background
We assessed the cost-effectiveness of adding a quadrivalent (6/11/16/18) human papillomavirus (HPV) vaccine to the current screening programme in the UK compared to screening alone.
Methods
A Markov model of the natural history of HPV infection incorporating screening and vaccination was developed. A vaccine that prevents 98% of HPV 6, 11, 16 and 18-associated disease, with a lifetime duration and 85% coverage, in conjunction with current screening was considered.
Results
Vaccination with screening, compared to screening alone, was associated with an incremental cost-effectiveness ratio of £21,059 per quality adjusted life year (QALY) and £34,687 per life year saved (LYS). More than 400 cases of cervical cancer, 6700 cases of cervical intraepithelial neoplasia and 4750 cases of genital warts could be avoided per 100,000 vaccinated girls. Results were sensitive to assumptions about the need for a booster, the duration of vaccine efficacy and discount rate.
Conclusion
These analyses suggest that adding a quadrivalent HPV vaccine to current screening in the UK could be a cost-effective method for further reducing the burden of cervical cancer.
doi:10.1186/1478-7547-6-4
PMCID: PMC2290741  PMID: 18279515

Results 1-6 (6)