Importance

Many cervical cancer screening strategies are now recommended in the United States, but the benefits, harms, and costs of each option are unclear.

Objective

To estimate the cost-effectiveness of 12 cervical cancer screening strategies.

Design, setting, and participants

The cross-sectional portion of this study enrolled a convenience sample of 451 English-speaking or Spanish-speaking women aged 21 to 65 years from September 22, 2014, to June 16, 2016, identified at women's health clinics in San Francisco. In this group, utilities (preferences) were measured for 23 cervical cancer screening-associated health states and were applied to a decision model of type-specific high-risk human papillomavirus (hrHPV)-induced cervical carcinogenesis. Test accuracy estimates were abstracted from systematic reviews. The evaluated strategies were cytologic testing every 3 years for women aged 21 to 65 years with either repeat cytologic testing in 1 year or immediate hrHPV triage for atypical squamous cells of undetermined significance (ASC-US), cytologic testing every 3 years for women age 21 to 29 years followed by cytologic testing plus hrHPV testing (cotesting), or primary hrHPV testing alone for women aged 30 to 65 years. Screening frequency, abnormal test result management, and the age to switch from cytologic testing to hrHPV testing (25 or 30 years) were varied. Analyses were conducted from both the societal and health care sector perspectives.

Main outcomes and measures

Utilities for 23 cervical cancer screening-associated health states (cross-sectional study) and quality-adjusted life-years (QALYs) and total costs for each strategy.

Results

Utilities were measured in a sociodemographically diverse group of 451 women (mean [SD] age, 38.2 [10.7] years; 258 nonwhite [57.2%]). Cytologic testing every 3 years with repeat cytologic testing for ASC-US yielded the most lifetime QALYs and conferred more QALYs at higher costs ($2166 per QALY) than the lowest-cost strategy (cytologic testing every 3 years with hrHPV triage of ASC-US). All cytologic testing plus hrHPV testing (cotesting) and primary hrHPV testing strategies provided fewer QALYs at higher costs. Adding indirect costs did not change the conclusions. In sensitivity analyses, hrHPV testing every 5 years with genotyping triage beginning at age 30 years was the lowest-cost strategy when hrHPV test sensitivity was markedly higher than cytologic test sensitivity or when hrHPV test cost was equated to the lowest reported cytologic test cost ($14).

Conclusions and relevance

Cytologic testing every 3 years for women aged 21 to 29 years with either continued cytologic testing every 3 years or switching to a low-cost hrHPV test every 5 years confers a reasonable balance of benefits, harms, and costs. Comparative modeling is needed to confirm the association of these novel utilities with cost-effectiveness.

Objective

To estimate the risk of cervical intraepithelial neoplasia grade 2, 2-3, 3, adenocarcinoma in situ, or cancer (CIN 2 or worse) among women with human immunodeficiency virus (HIV)- and non-HIV-associated immunosuppression.

Methods

We performed a case-control study of 20,146 women with incident CIN 2 or worse and 5:1 age-matched, incidence-density selected women in a control group (n=100,144) enrolled in an integrated health care system from 1996 to 2014. Adjusted rate ratios (RRs) from conditional logistic regression were obtained for HIV status (stratified by CD4 T-cells), solid organ transplant history, and immunosuppressive medication use.

Results

Risk of CIN 2 or worse was increased among women with HIV (n=36 women in the case group and 79 women in the control group; adjusted RR 2.0, 95% CI 1.3-3.0) compared with those without HIV and in solid organ transplant recipients (n=51 women in the case group and 68 women in the control group; RR 3.3, 95% CI 2.3-4.8) compared with women without a prior transplant. The highest risks were among women with HIV and less than 200 CD4 T-cells/microliter (n=9 women in the case group and eight women in the control group; RR 5.6, 95% CI 2.1-14.7) compared with those without HIV and in solid organ transplant recipients prescribed three or greater immunosuppressive medication classes (n=32 women in the case group and 33 women in the control group; RR 4.1, 95% CI 2.5-6.8) compared with women without a prior transplant and zero medication classes. No increased risks were observed for women with HIV and 500 or greater CD4 T-cells/microliter (n=9 women in the case group and 43 women in the control group; RR 0.8, 95% CI 0.4-1.7) compared with those without HIV or women without prior solid organ transplantation prescribed two or fewer immunosuppressive medication classes (n=1,262 women in the case group and 6,100 women in the control group; RR 0.95, 95% CI 0.89-1.01) compared with women without and a prior transplant and zero medication classes.

Conclusion

Risk of CIN 2 or worse is increased in women with a prior solid organ transplant or who have HIV and CD4 cells/microliter less than 500 but not in women with HIV and higher CD4 levels or in women without a prior solid organ transplant but who are prescribed only one or two immunosuppressive medication classes.

It is unknown whether the HPV vaccine is effective in immunocompromised women during catch-up ages. We performed a case-control study of 4,357 women with incident CIN2+ (cases) and 5:1 age-matched, incidence-density selected controls (N = 21,773) enrolled in an integrated health care system from 2006 to 2014. Vaccine effectiveness was estimated from multivariable conditional logistic regression models, with results stratified by immunosuppression history, defined as prior HIV infection, solid organ transplant history, or recently prescribed immunosuppressive medications. HPV vaccination resulted in a 19% reduction in CIN2+ rates for women without an immunosuppression history but a nonsignificant 4% reduction for women with an immunosuppression history. Further research is needed to evaluate whether catch-up HPV vaccine effectiveness varies by immunosuppression status, especially given the recent approval of the HPV vaccine for adults up to 45 years of age.

Background

The population effectiveness of human papillomavirus (HPV) catch-up vaccination, defined in the USA as first vaccination at ages 13-26 years, has not been studied extensively. We aimed to assess the risk of cervical intraepithelial neoplasia (CIN) 2, CIN3, adenocarcinoma in situ, or cancer (CIN2+ and CIN3+) by prior HPV vaccination status, age at first dose, and number of doses in women participating in a screening programme within a large integrated health-care system.

Methods

We performed a nested case-control study of women enrolled in Kaiser Permanente Northern California (an integrated health-care delivery system in California, USA). Cases were women with CIN2+ or CIN3+ confirmed by histology between Jan 1, 1995, and June 30, 2014, and incidence density-selected controls were age-matched women without CIN2+ or CIN3+ at the time each case occurred. For each case, we randomly selected five controls. Cases and controls were aged 26 years or younger when the HPV quadrivalent vaccine became available in 2006. Rate ratios (RRs) from conditional logistic regression were estimated by age at time of first HPV quadrivalent vaccine dose (14-17 years, 18-20 years, and ≥21 years), and number of doses (one, two, and three or more doses) compared with no prior vaccination, with adjustment for smoking, hormonal contraceptive prescription, race or ethnicity, sexually transmitted infections, immunosuppression, parity, and number of outpatient visits.

Findings

4357 incident CIN2+ cases and 21 773 matched controls were included in the study. Of these, 1849 were incident CIN3+ cases with 9242 matched controls. The youngest age at time of first vaccination was 14 years. One or more HPV vaccine doses conferred protection against CIN2+ (RR 0·82, 95% CI 0·73-0·93) and CIN3+ (0·77, 0·64-0·94). We found the strongest protection against CIN2+ in women who had received at least three vaccine doses and had received their first dose aged 14-17 years (0·52, 0·36-0·74) or aged 18-20 years (0·65, 0·49-0·88). No significant protection was found in women aged 21 years or older at time of first dose (0·94, 0·81-1·09). Inferences were similar for CIN3+, but with stronger effects for women who received at least three vaccine doses and had received their first dose aged 14-17 years (0·27, 0·13-0·56) or aged 18-20 years (0·59, 0·36-0·97).

Interpretation

Catch-up quadrivalent HPV vaccination with three doses was effective against CIN2+ and CIN3+ in girls and women aged 14-20 years at time of first vaccine dose but not for women aged 21 years and older at first dose.

Funding

US National Cancer Institute.

Transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is possible among symptom-free individuals. Patients are avoiding medically necessary healthcare visits for fear of becoming infected in the healthcare setting. We screened 489 symptom-free healthcare workers for SARS-CoV-2 and found no positive results, strongly suggesting that the prevalence of SARS-CoV-2 was <1%.

BACKGROUND: Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is possible among symptom-free individuals and some patients are avoiding medically necessary healthcare visits for fear of becoming infected in the healthcare setting. Limited data are available on the point prevalence of SARS-CoV-2 infection in symptom-free U.S. healthcare workers (HCW). METHODS: A cross-sectional convenience sample of symptom-free HCWs from the metropolitan area surrounding Minneapolis and St. Paul, Minnesota was enrolled between April 20 th and June 24 th , 2020. A participant self-collected nasopharyngeal swab (NPS) was obtained. SARS-CoV-2 infection was assessed via polymerase chain reaction. Participants were queried about their willingness to repeat a self-collection NPS for diagnostic purposes. We had >95% power to detect at least one positive test if the true underlying prevalence of SARS-CoV2 was ≥1%. RESULTS: Among n=489 participants 80% were female and mean age±SD was 41±11. Participants reported being physicians (14%), nurse practitioners (8%), physician's assistants (4%), nurses (51%), medics (3%), or other which predominantly included laboratory technicians and administrative roles (22%). Exposure to a known/suspected COVID-19 case in the 14 days prior to enrollment was reported in 40% of participants. SARS-CoV-2 was not detected in any participant. Over 95% of participants reported a willingness to repeat a self-collected NP swab in the future. CONCLUSIONS: The point prevalence of SARS-CoV-2 infection was likely <1% in a convenience sample of symptom-free Minnesota healthcare workers from April 20 th and June 24 th , 2020. Self-collected NP swabs are well-tolerated and a viable alternative to provider-collected swabs to preserve PPE.