Numerous national guidelines now include primary human papillomavirus (HPV) testing as a recommended screening option for cervical cancer in the United States yet little is known regarding screening intentions for this specific screening strategy or interventions that may increase uptake. Gain- and loss-framed messaging can positively impact health behaviors; however, there is mixed evidence on which is more effective for cervical cancer screening, with no published evidence examining HPV testing. To help address this gap, this study compared the effects of message framing on screening knowledge and intentions related to primary HPV testing. We randomized females aged 21–65 (n = 365) to receive brief messaging about cervical cancer screening with either gain- or loss-framing. In January–February 2020, participants completed pretest and posttest measures evaluating cervical cancer knowledge, beliefs, and intentions to be screened using HPV testing. We used generalized estimating equations to model message and framing effects on screening outcomes, controlling for age, education, race, and baseline measures. In comparison to pretest, messaging significantly increased HPV-related screening intentions [adjusted OR (aOR): 2.4 (1–3.5)] and knowledge [aOR: 1.7 (1.2–2.4)], perceived effectiveness of HPV testing [aOR: 4.3 (2.8–6.5)], and preference for primary HPV screening [aOR: 3.2 (1.2–8.5)], regardless of message framing. For all outcomes, no significant interaction by message framing was observed. Brief public health messaging positively impacted HPV-related screening intentions, knowledge, and beliefs, independent of message framing. In conjunction with other strategies, these results suggest that messaging could be an effective tool to increase uptake of primary HPV testing.

Prevention Relevance:

Primary HPV tests are more sensitive and offer greater reassurance than Pap tests alone yet use for routine cervical cancer screening remains low. Brief public health messaging can positively impact awareness, knowledge, and screening intention regarding primary HPV testing. Messaging campaigns paired with other strategies can increase uptake across populations.

See related Spotlight, p. 823

Population-based cervical cancer screening guidelines have evolved in the last two decades from annual screening with cytology (or Pap testing) to less frequent screening using human papillomavirus (HPV) testing with or without cytology (1). Building upon growing evidence that HPV tests are more sensitive and offer greater reassurance than cytology alone (2), numerous national guidelines now include primary HPV testing as a recommended or even preferred option for screening: beginning with 2015 interim guidelines (3) that included it as an option for screening, followed by 2018 United States Preventive Services Task Force (USPSTF) guidelines that added it as a recommended option for women aged 30–65 (1), and most recently with 2020 American Cancer Society (ACS) guidelines that stated it as the preferred screening modality for cervical cancer screening for females aged 25 through 65 (4). Little is known regarding population awareness and knowledge of primary HPV testing or other factors that may shape screening intentions for this modality (5, 6).

Public health messaging can increase cancer screening, with mixed evidence indicating that message framing can differentially affect behavioral outcomes (7). Guided by prospect theory (8), messaging can be framed to communicate the benefits of engaging in a preventive behavior (gain-framed), risks of not completing a behavior (loss-framed), or simply the facts (neutral). Prior research suggests that individuals may be more likely to respond favorably to gain-framed messages than loss-framed for behaviors perceived as low-risk (9). For cancer screening, there is mixed evidence on which is more effective to increase screening intentions (10, 11), with no published evidence examining message framing effects on intentions to be screened using primary HPV testing.

Given the rapidly changing field of cervical cancer screening, spurred by new screening technologies and steadily increasing HPV vaccination, there is a key need to identify effective and low-touch strategies to increase awareness of changes in guidelines and ensure the benefits of population-based cervical cancer screening across the population. Even nearly a decade after 2012 consensus guidelines, which recommended against annual screening, research continues to show persistent challenges with changing established cervical cancer screening practices, with many studies indicating patients' limited knowledge of guidelines and lack of provider recommendation as barriers to adoption of extended screening guidelines using 3-year Pap testing or 5-year co-testing (screening simultaneously using cytology and HPV testing) (5, 6, 12). Given the more recent inclusion of primary HPV testing alone as a preferred screening strategy, there is a great need to explore messaging strategies to inform patients of the current evidence-based recommendations to increase the uptake of primary HPV testing. To address this gap, we aimed to test the effect of message framing on HPV-related screening knowledge, beliefs, and intentions among females eligible for routine cervical cancer screening.

Recruitment

We utilized the online crowdsourcing platform Amazon Mechanical Turk (MTurk), which is increasingly used for behavioral research (13), to identify and recruit respondents who met the following criteria: (i) English-speaking adult females in the United States; (ii) eligible for routine cervical cancer screening (no history of CIN2+, cervical cancer, or in utero diethylstilbestrol exposure; not HIV+ or otherwise immunocompromised); and (iii) held Master MTurk Qualifications (determined by Amazon to those who consistently submit reliable results). Following recruitment (January–February 2020), eligible respondents continued to the secure survey platform (Qualtrics). Interested respondents were then asked to review the consent form in the survey platform and provide written informed consent electronically before enrolling in the study.

Enrolled participants first completed the pretest questionnaire assessing demographics, cervical cancer screening history, and screening outcomes (knowledge, beliefs, and intentions). Participants then viewed a randomly assigned message (gain- or loss-framed) and completed the posttest questionnaire. Participants completed all study procedures in 25 minutes on average and were compensated $5 for their time. The survey was designed to assess the effect of messaging on changes in screening guidelines overall including, but not limited to, primary HPV testing. As such, the study was powered to detect a minimum difference of 20% decrease in either arm of experiment (200 participants each) based on our prior study where 63% of participants believed they should receive annual Pap testing (5). This approach is similar to other studies testing effects of message framing on multicomponent guidelines (10, 11, 14, 15). All activities were conducted after approval by the University of Pennsylvania Institutional Review Board and in accordance with the U.S. Common Rule. Messaging content and outcomes We drafted the messaging using publicly available CDC materials (https://www.cdc.gov/cancer/cervical/basic_info/screening.htm) and refined it for clarity, burden, and comprehension following pilot testing. The message consisted of neutral information about cervical cancer and screening recommendations, and began and ended with either gain-framed or loss-framed phrases (see Supplementary Table S1). Participants reported HPV testing intention by responding to the statement: “I intend to have an HPV test in the next 12 months” (Yes, No, or I don't know). Screening preference was evaluated by the question: “If given the option by your doctor, what type of cervical cancer screening test would you choose to have?” (Pap smear only, HPV test only, Pap smear and HPV test at the same time, Whichever test my doctor recommended, or I don't know). To assess perceived effectiveness, participants answered the question: “In your opinion, how successful is the HPV test at detecting cervical cancer in its earliest stages?” (5-point scale; 1 = Not successful at all; 5 = Very successful). To assess likelihood of following their doctor's recommendation for HPV testing and concern over not having a Pap test, we asked participants to consider: “If your doctor recommended HPV testing alone as the best option for cervical cancer screening for you, how likely would you be to follow her or his recommendation?” (4-point scale; 1 = Very unlikely; 4 = Very likely) and “how much concern would you feel about not having a Pap smear?” (4-point scale; 1 = No concern; 4 = Much concern). We assessed screening knowledge using 10 items, adapted from previous surveys (12, 16). All outcomes were assessed at pretest and posttest and dichotomized for analysis following similar studies. Analysis From the full study sample (n = 398), we excluded participants who are not eligible based on their age for routine cervical cancer screening based on USPSTF and ACS screening guidelines (n = 48; ref. 1). Women over 65 who are still eligible for cervical cancer screening are not recommended to be screened using primary HPV testing every 5 years (1, 4). While USPSTF guidelines do not recommend primary HPV testing for females under age 30, we included this group as they will be eligible as they age and ACS guidelines include ages 25 through 65 (4). We assessed baseline characteristics and differences between randomized groups using descriptive statistics and Fisher exact test. We used generalized estimating equations to model population-level effects of messaging on screening outcomes, accounting for age, education, race, and repeated measures. We tested for effect modification by frame based on significance of the interaction term. All tests were considered statistically significant at P < 0.05 and analyses were performed in Stata 15 (StataCorp LP). Participant characteristics The demographic characteristics of the 365 participants are displayed in Table 1. The majority of respondents (74.0%) identified as white with 9.3% and 6.0% identifying as Black and Asian, respectively. About half (50.1%) had a bachelor's degree or higher, 36.8% lived in a small city or rural location, and nearly all U.S. states (46/50) were represented. Similar to national estimates of ever-screening (17), most of the participants (88.8%) had received a Pap test before, but only 36.2% had ever received an HPV test. Randomization of messaging was nearly equal with 49.6% (n = 181) and 50.4% (n = 184) of participants receiving gain- or loss-framed messaging, respectively. There were no significant differences by baseline sociodemographics or screening between randomized groups. Table 1. Participant baseline characteristics by received message framing, n (%). CharacteristicsGain-framed (n = 181)Loss-framed (n = 184)Total (n = 365) Age (years) 21–29 27 (14.9) 21 (11.4) 48 (13.2) 30–39 67 (37.0) 78 (42.4) 145 (39.7) 40–49 58 (32.0) 55 (29.9) 113 (31.0) 50–59 21 (11.6) 26 (14.1) 47 (12.9) 60–65 8 (4.4) 4 (2.2) 12 (3.3) Race/Ethnicity Asian 10 (5.5) 12 (6.5) 22 (6.0) Hispanic/Latina/Latinx 7 (3.9) 11 (6.0) 18 (4.9) Non-Hispanic Black 18 (9.9) 16 (8.7) 34 (9.3) Non-Hispanic White 135 (74.6) 135 (73.4) 270 (74.0) Multiracial/Other 11 (6.1) 10 (5.4) 21 (5.6) Gender identity Female 173 (95.6) 180 (97.8) 353 (96.7) Other gender 8 (4.4) 4 (2.2) 12 (3.3) Sexual identity Heterosexual 162 (90.0) 154 (86.7) 316 (86.8) Bisexual 15 (8.3) 18 (9.8) 33 (9.1) Lesbian, Gay, or Queer 1 (0.6) 7 (3.8) 8 (2.2) Other/Prefer Not to Say 2 (1.1) 5 (2.7) 7 (1.9) Education High school 26 (14.4) 18 (9.8) 44 (12.1) Some college 34 (18.8) 42 (22.8) 76 (20.8) Associate's degree 32 (17.7) 30 (16.3) 62 (17.0) Bachelor's degree 71 (39.2) 74 (40.2) 145 (39.7) Graduate degree 18 (9.9) 20 (10.9) 38 (10.4) Annual income ($)
<30,000 33 (18.2) 40 (21.7) 73 (20.0)
30,000–49,999 42 (23.2) 46 (25.0) 88 (24.1)
50,000–99,999 77 (42.5) 69 (37.5) 146 (40.0)
≥100,000 29 (16.0) 29 (15.8) 58 (15.9)
Health insurance
Private 138 (76.2) 113 (61.4) 251 (68.8)
Public/Medicare/Veteran 27 (14.9) 43 (23.3) 70 (19.2)
Uninsured 16 (8.8) 28 (15.2) 44 (12.1)
Place of residence
Large city 51 (28.2) 52 (28.3) 103 (28.2)
Suburban 63 (34.8) 65 (35.3) 128 (35.1)
Small city/town 46 (25.4) 48 (26.1) 94 (25.8)
Rural 21 (11.6) 19 (10.3) 40 (11.0)
Health history (% yes)
Routine check-up in past 2 yrs 143 (79.0) 146 (79.4) 289 (79.2)
Currently smokes every day* 44 (24.3) 29 (15.9) 73 (20.1)
Ever had Pap test 159 (87.9) 165 (89.7) 324 (88.8)
Ever had HPV test 64 (35.4) 68 (37.0) 132 (36.2)
CharacteristicsGain-framed (n = 181)Loss-framed (n = 184)Total (n = 365)
Age (years)
21–29 27 (14.9) 21 (11.4) 48 (13.2)
30–39 67 (37.0) 78 (42.4) 145 (39.7)
40–49 58 (32.0) 55 (29.9) 113 (31.0)
50–59 21 (11.6) 26 (14.1) 47 (12.9)
60–65 8 (4.4) 4 (2.2) 12 (3.3)
Race/Ethnicity
Asian 10 (5.5) 12 (6.5) 22 (6.0)
Hispanic/Latina/Latinx 7 (3.9) 11 (6.0) 18 (4.9)
Non-Hispanic Black 18 (9.9) 16 (8.7) 34 (9.3)
Non-Hispanic White 135 (74.6) 135 (73.4) 270 (74.0)
Multiracial/Other 11 (6.1) 10 (5.4) 21 (5.6)
Gender identity
Female 173 (95.6) 180 (97.8) 353 (96.7)
Other gender 8 (4.4) 4 (2.2) 12 (3.3)
Sexual identity
Heterosexual 162 (90.0) 154 (86.7) 316 (86.8)
Bisexual 15 (8.3) 18 (9.8) 33 (9.1)
Lesbian, Gay, or Queer 1 (0.6) 7 (3.8) 8 (2.2)
Other/Prefer Not to Say 2 (1.1) 5 (2.7) 7 (1.9)
Education
High school 26 (14.4) 18 (9.8) 44 (12.1)
Some college 34 (18.8) 42 (22.8) 76 (20.8)
Associate's degree 32 (17.7) 30 (16.3) 62 (17.0)
Bachelor's degree 71 (39.2) 74 (40.2) 145 (39.7)
Graduate degree 18 (9.9) 20 (10.9) 38 (10.4)
Annual income (\$)
<30,000 33 (18.2) 40 (21.7) 73 (20.0)
30,000–49,999 42 (23.2) 46 (25.0) 88 (24.1)
50,000–99,999 77 (42.5) 69 (37.5) 146 (40.0)
≥100,000 29 (16.0) 29 (15.8) 58 (15.9)
Health insurance
Private 138 (76.2) 113 (61.4) 251 (68.8)
Public/Medicare/Veteran 27 (14.9) 43 (23.3) 70 (19.2)
Uninsured 16 (8.8) 28 (15.2) 44 (12.1)
Place of residence
Large city 51 (28.2) 52 (28.3) 103 (28.2)
Suburban 63 (34.8) 65 (35.3) 128 (35.1)
Small city/town 46 (25.4) 48 (26.1) 94 (25.8)
Rural 21 (11.6) 19 (10.3) 40 (11.0)
Health history (% yes)
Routine check-up in past 2 yrs 143 (79.0) 146 (79.4) 289 (79.2)
Currently smokes every day* 44 (24.3) 29 (15.9) 73 (20.1)
Ever had Pap test 159 (87.9) 165 (89.7) 324 (88.8)
Ever had HPV test 64 (35.4) 68 (37.0) 132 (36.2)

Note: All percentages may not total to 100% due to missingness. No statistically significant (P < 0.05) differences by frame except for current smoking status (indicated by asterisk).

Effects of messaging

Relative to pretest, exposure to messaging significantly increased intentions to receive HPV testing [adjusted OR (aOR): 2.4 (1.6–3.5)], preference for HPV testing alone [aOR: 3.2 (1.2–8.5)], and perceived effectiveness of HPV testing against cervical cancer [aOR: 4.3 (2.8, 6.5)]. Guideline-related knowledge on Pap testing, cotesting, primary HPV testing, and recommended stopping age all increased significantly from pretest to posttest (Table 2). General cervical cancer knowledge also increased significantly for four of the six items. We found no significant differences in likelihood to undergo HPV testing if recommended by their provider or concern over not receiving a Pap test. For all outcomes, message framing did not have any significant moderating effects.

Table 2.

Effect of messaging on women's screening intentions, beliefs, and knowledge related to primary HPV testing for routine cervical cancer screening (n = 365).

Pretest n (%)Posttest n (%)aORa (95% CI)
Gain-Framed n = 181Loss-Framed n = 184Gain-Framed n = 181Loss-Framed n = 184Posttest difference
Screening intention
HPV testing intention (% Yes) 42 (23.2) 43 (23.4) 73 (40.3) 68 (37.0) 2.4 (1.6–3.5)
Screening beliefs
Screening preference (% HPV test only) 6 (3.31) 7 (3.8) 16 (8.8) 20 (10.9) 3.2 (1.2–8.5)
Effectiveness of HPV testing (% Pretty/Very Successful) 89 (49.2) 88 (47.8) 146 (80.7) 142 (77.2) 4.3 (2.8–6.5)
Likelihood of undergoing primary HPV testing, if recommended by provider (% Likely/Very Likely) 131 (72.4) 120 (65.2) 122 (67.4) 122 (66.3) 0.8 (0.6–1.1)
Concerned about not having a Pap test (% Moderate/Much concern) 55 (30.4) 68 (37.0) 52 (28.7) 50 (27.2) 0.8 (0.6–1.2)
Screening knowledge
How often is a female your age recommended to be screened for cervical cancer if tested using Pap smear alone? (% Correct: Every 3 yrs) 35 (19.3) 38 (20.7) 157 (86.7) 156 (84.8) 33.9 (18.8–61.2)
How often is a female your age recommended to be screened for cervical cancer if tested using Pap smear and HPV testing at the same time? (% Correct: Every 5 yrs) 15 (8.3) 19 (10.3) 106 (58.6) 122 (66.3) 19.6 (10.6–36.5)
How often is a female your age recommended to be screened for cervical cancer if tested using HPV testing alone? (% Correct: Every 5 yrs) 12 (6.6) 17 (9.2) 106 (58.6) 125 (67.9) 24.7 (12.2–50.2)
At what age are most females recommended to stop being screening for cervical cancer? (% Correct: Age 65) 46 (25.4) 48 (26.1) 169 (93.4) 173 (94.0) 45.6 (22.9–90.8)
Females should get screened for cervical cancer only if they have symptoms. (% Correct: False) 169 (93.4) 166 (90.2) 172 (95.0) 176 (95.7) 1.1 (0.7–1.8)
Screening tests can help prevent cervical cancer. (% Correct: True) 118 (65.2) 141 (76.6) 142 (78.5) 146 (79.4) 1.9 (1.3–2.8)
There is no treatment for cervical cancer. (% Correct: False) 154 (85.1) 152 (82.6) 165 (91.2) 166 (90.2) 1.8 (1.0–3.3)
HPV causes cervical cancer. (% Correct: True) 132 (72.9) 132 (71.7) 148 (81.8) 151 (82.1) 1.7 (1.2–2.4)
HPV can cause abnormal Pap smears. (% Correct: True) 122 (67.4) 128 (69.6) 131 (72.4) 146 (79.4) 1.2 (0.8–1.7)
Pap smears look for changes on your cervix that indicate you are at risk for cancer. (% Correct: True) 148 (81.8) 155 (84.2) 169 (93.4) 170 (92.4) 3.1 (1.7–5.6)
Pretest n (%)Posttest n (%)aORa (95% CI)
Gain-Framed n = 181Loss-Framed n = 184Gain-Framed n = 181Loss-Framed n = 184Posttest difference
Screening intention
HPV testing intention (% Yes) 42 (23.2) 43 (23.4) 73 (40.3) 68 (37.0) 2.4 (1.6–3.5)
Screening beliefs
Screening preference (% HPV test only) 6 (3.31) 7 (3.8) 16 (8.8) 20 (10.9) 3.2 (1.2–8.5)
Effectiveness of HPV testing (% Pretty/Very Successful) 89 (49.2) 88 (47.8) 146 (80.7) 142 (77.2) 4.3 (2.8–6.5)
Likelihood of undergoing primary HPV testing, if recommended by provider (% Likely/Very Likely) 131 (72.4) 120 (65.2) 122 (67.4) 122 (66.3) 0.8 (0.6–1.1)
Concerned about not having a Pap test (% Moderate/Much concern) 55 (30.4) 68 (37.0) 52 (28.7) 50 (27.2) 0.8 (0.6–1.2)
Screening knowledge
How often is a female your age recommended to be screened for cervical cancer if tested using Pap smear alone? (% Correct: Every 3 yrs) 35 (19.3) 38 (20.7) 157 (86.7) 156 (84.8) 33.9 (18.8–61.2)
How often is a female your age recommended to be screened for cervical cancer if tested using Pap smear and HPV testing at the same time? (% Correct: Every 5 yrs) 15 (8.3) 19 (10.3) 106 (58.6) 122 (66.3) 19.6 (10.6–36.5)
How often is a female your age recommended to be screened for cervical cancer if tested using HPV testing alone? (% Correct: Every 5 yrs) 12 (6.6) 17 (9.2) 106 (58.6) 125 (67.9) 24.7 (12.2–50.2)
At what age are most females recommended to stop being screening for cervical cancer? (% Correct: Age 65) 46 (25.4) 48 (26.1) 169 (93.4) 173 (94.0) 45.6 (22.9–90.8)
Females should get screened for cervical cancer only if they have symptoms. (% Correct: False) 169 (93.4) 166 (90.2) 172 (95.0) 176 (95.7) 1.1 (0.7–1.8)
Screening tests can help prevent cervical cancer. (% Correct: True) 118 (65.2) 141 (76.6) 142 (78.5) 146 (79.4) 1.9 (1.3–2.8)
There is no treatment for cervical cancer. (% Correct: False) 154 (85.1) 152 (82.6) 165 (91.2) 166 (90.2) 1.8 (1.0–3.3)
HPV causes cervical cancer. (% Correct: True) 132 (72.9) 132 (71.7) 148 (81.8) 151 (82.1) 1.7 (1.2–2.4)
HPV can cause abnormal Pap smears. (% Correct: True) 122 (67.4) 128 (69.6) 131 (72.4) 146 (79.4) 1.2 (0.8–1.7)
Pap smears look for changes on your cervix that indicate you are at risk for cancer. (% Correct: True) 148 (81.8) 155 (84.2) 169 (93.4) 170 (92.4) 3.1 (1.7–5.6)

aEach GEE model assesses the adjusted odds of the average outcome at posttest in reference to average outcome at pretest and includes an interaction term for the frame. All models accounted for age, education, race, and repeated measures.

This study highlights the continued importance of public health messaging for increasing evidence-based HPV testing for cervical cancer screening. Half of our sample completed higher education and the majority had been screened before using cytology, but only a minority had accurate baseline knowledge of HPV testing or recommended guidelines. About two-thirds of the sample would undergo primary HPV testing if recommended by their provider; however, about 30% of participants remained concerned about not receiving a Pap test and may need additional counseling from their providers. Similar to a previous study (11) on message framing for cytology-based cervical cancer screening, we did not observe any significant framing effects; however, this may be because both gain- and loss-framed messaging substantially increased screening knowledge and other outcomes. Findings indicate that brief messaging can influence women to consider utilizing a newer, more effective screening modality, along with an increased understanding as to the reason behind the change in screening recommendations.

This study is not without limitations but begins to address a significant gap in how to address patients' limited knowledge and uptake of primary HPV testing. Although this study relies on self-report data and is therefore limited by lack of direct measurement of screening behaviors, self-reported screening intentions have been shown to predict screening behaviors (18), suggesting that our messaging could dramatically increase uptake of primary HPV testing. The majority of the sample had been screened for cervical cancer before; however, this reflects the general population of women eligible for screening in the United States, with about 93% of women aged 21–65 ever being screened with cytology (17), and it does not retract from the study purpose of understanding how we could utilize message framing to increase uptake of newer screening strategies—namely primary HPV testing alone—among screened and never screened populations. While the sample may not reflect all populations of women in the United States, our recruitment strategy enabled us to gather perspectives from a geographically diverse sample rather than being restricted to a single area or institution. Future research is needed to test the effect of messaging on screening behaviors and beliefs across diverse populations.

Given the rapidly changing landscape of cervical cancer screening, effective strategies that increase awareness and uptake of evidence-based screening are needed. Lags in screening knowledge can decrease timely uptake and therefore effectiveness of population-based screening, particularly in populations with greater cervical cancer burden (6). Our findings suggest that providing brief messaging can increase awareness, knowledge, and intentions of primary HPV testing, regardless of frame. Although messaging is an important public health tool that can be deployed widely and at relatively low-cost, additional research is needed to identify other strategies to ensure all females are aware of the importance of cervical cancer screening and available screening modalities and receive recommended screening.

No disclosures were reported.

S.N. Ogden: Conceptualization, resources, validation, investigation, visualization, methodology, writing–original draft, project administration, writing–review and editing. E.A. Leskinen: Conceptualization, resources, data curation, validation, investigation, visualization, methodology, project administration, writing–review and editing. E.A. Sarma: Conceptualization, resources, validation, investigation, visualization, methodology, project administration, writing–review and editing. J.V. Wainwright: Conceptualization, resources, validation, investigation, visualization, methodology, project administration, writing–review and editing. K.A. Rendle: Conceptualization, resources, data curation, software, formal analysis, supervision, funding acquisition, validation, investigation, visualization, methodology, project administration, writing–review and editing.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the NCI. This research was partially funded by the University of Pennsylvania Perelman School of Medicine Patient-Centered Outcomes Research Pilot Program (to K.A. Rendle, principal investigator). S.N. Ogden is supported by a training grant from the National Institute on Drug Abuse (T32DA041898).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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