Prevalence of high-risk HPV by RNA assay in home self-collected samples among underscreened people in North Carolina

SUMMARY

High-risk HPV prevalence was 16% using an oncogenic RNA assay in home-collected samples among low-income, underscreened individuals in North Carolina.

Background:

Low-income and uninsured people with a cervix (PWC) are at highest risk of being underscreened for cervical cancer. We evaluated the prevalence of high-risk HPV (hrHPV) on home self-collected samples, as well as rates of in-clinic follow-up and risk factors associated with hrHPV positivity in this at-risk population.

Methods:

My-Body-My-Test-3 was conducted between 2016-2019 in North Carolina among individuals aged 25-64 years, overdue for cervical cancer screening, and with incomes of <250% of the U.S. Federal Poverty Level. Our analytic sample included participants randomized to the self-collection arm who returned self-collected cervico-vaginal brush samples for HPV testing (n=329). Samples were tested for 14 hrHPV types by an HPV RNA assay and further genotyped for HPV 16 and HPV 18/45. We examined behavioral risk factors for hrHPV positivity using logistic regression and between-subjects t-tests.

Results:

HrHPV RNA prevalence was 16% (n=52/329) in self-collected samples. Of the hrHPV-positive participants, 24 (46%) presented for in-clinic cervical cancer screening, compared to 56 (20%) of hrHPV-negative participants. Those with ≥2 sexual partners in the past year were twice as likely to be hrHPV positive in adjusted analyses (adjusted OR=2.00 (95% CI: 1.03-3.88). HrHPV-positive and negative participants had similar attitudes towards screening, with the exception of hrHPV-positive participants who reported a lower perceived risk of cervical cancer than those who were hrHPV-negative (p<.05).

Conclusion:

The hrHPV RNA prevalence was similar to findings in other underscreened PWC in the US. Efforts to reach underscreened PWC is critical for cervical cancer prevention. Future studies aimed at home self-collection should address methods of increasing clinic attendance and completion of treatment among those with HPV-positive results.

INTRODUCTION

Invasive cervical cancer (ICC) is preventable with routine screening. However, an estimated one in five people with a cervix (PWC) in the United States (US) are overdue for screening. [1] Despite efforts to increase screening uptake, over 12,000 ICC diagnoses are made annually in the US, and over 50% of these are among underscreened individuals. [2]

Low-income, uninsured and publicly insured PWC are at highest risk of being underscreened. [3] A promising new screening method is the home-based self-collection kit that screens for the 14 types of high-risk HPV (hrHPV), the causal agent of almost all ICC. When mailed to homes, HPV self-collection has the potential to reach individuals who do not readily access healthcare. Robust data show comparable sensitivity for self-collected home testing relative to provider-collected hrHPV testing for the detection of high-grade cervical precancer. [4] Home testing is also highly acceptable in diverse communities, [5,6] including in low-income, underscreened PWC in North Carolina (NC). [7-9] However, few studies have evaluated the prevalence of hrHPV and risk factors for infection specific to underscreened US populations through self-collected sampling. [10,11] Most studies are from clinic-based populations, which generally reflect a more regularly screened population with access to healthcare rather than underscreened individuals. Furthermore, no studies to date directly compare attitudes and perceptions towards cervical cancer and screening of PWC with hrHPV infection with those who are uninfected. Therefore, we present baseline survey data from My-Body-My-Test-3 (MBMT-3), a randomized control trial (RCT) that assessed impact of mailed HPV self-collection on completion of cervical cancer screening, to better understand the prevalence of hrHPV and factors associated with hrHPV positivity in self-collected samples in a group of low-income, underscreened PWC.

METHODS

Study participants and procedures

MBMT-3 was conducted in NC between 2016-2019. Recruitment procedures and enrollment protocols were described previously. [12] Briefly, participants were recruited by advertisements on printed materials (flyers, posters, roadside signs, buses and newspaper), online (primarily on Cragistlis.org) and on the radio. Information was also disseminated at community events that provided services to low-income individuals. Those who called the toll-free study hotline run by American Sexual Health Association (ASHA) were screened for eligibility over the phone, while those recruited in person by study staff at community events completed eligibility in person. The study website also had a short online eligibility questionnaire where study staff can review the information and follow-up by phone with potentially eligible individuals. Eligibility criteria were being one year overdue for screening per U.S. national guidelines [13] (self-reported as not having had a Pap smear in the past 4 years or HPV test in the past 6 years), age 25-64 years, income <250% of the U.S. Federal Poverty Level, uninsured, or enrolled in Medicaid or Medicare and living within the catchment area of a study-associated clinic.

Demographic and behavioral data were collected through a pre-intervention eligibility screener and baseline questionnaire.. Once signed informed consent and health information privacy forms were returned via mail, participants randomized to the intervention arm were mailed HPV test kits with instructions to self-collect a cervico-vaginal sample and return it by mail for testing.

The Viba brush (Rover Medical Devices, B.V., The Netherlands) was used for self-collection, and each sample was suspended in Aptima specimen transfer medium (STM, Hologic, Inc, San Diego, CA), a transport medium approved for mailing via US Postal Service and validated to keep specimens stable for HPV RNA testing up to 60 days at room temperature. [14] Self-collection kits were mailed back to University of North Carolina, de-identified, and sent to LabCorp in Burlington, NC, for laboratory testing. Samples were tested for positivity with 14 hrHPV types using Aptima HPV assay, an FDA-approved transcription mediated amplification assay that detects hrHPV E6/E7 mRNA with comparable sensitivity and increased specificity as DNA tests for detecting clinically relevant high-grade cervical intraepithelial neoplasia or more severe (CIN2+) disease. [15] HrHPV-positive samples were then tested for E6/E7 mRNA for both HPV16 and HPV18/45, [16] the HPV types most prevalent in ICC. [17]

Trained interviewers delivered hrHPV results to participants by phone and provided brief counseling. While all study participants were offered assistance in scheduling in-clinic appointments, counseling was specific to participants’ hrHPV results. Those who tested negative received counseling that it is “probably safe for you to wait 2 years before you get screened for cervical cancer again,” however it was recommended that they confirm self-collected results with a free in-clinic screening with Pap and HPV testing. Those who tested positive were “strongly recommended to go in for Pap smear as soon as possible” to determine next steps in clinical management. [12] Study partner clinics offered provider-collected hrHPV and Pap cytology co-screening using ThinPrep cervical spatula and endocervical brush with samples preserved in PreservCyt solution (Hologic, Bedford, MA). In-clinic screening completion was tracked for 6 months following study enrollment using clinic medical records, as permitted by participants’ authorization. Study staff also requested medical records from clinics for participants who reported attending a non-study affiliated clinic. Participants received US$25 for completing baseline questionnaire regardless of whether participants completed screening.

The UNC Institutional Review Board approved all study procedures.

Measures

We utilized data from the eligibility screener and baseline questionnaire on screening history and sociodemographic characteristics. The baseline questionnaire included behavioral questions that assessed attitudes towards cervical cancer and screening, which was verified through cognitive interviewing prior to study initiation. The 4-point response scale was coded 4 for strongly agree, 3 for somewhat agree, 2 for somewhat disagree and 1 for strongly disagree. We coded responses of “don’t know” or “refuses” as missing. Question selection was guided by the Health Belief Model [18] and informed by prior literature on associations with between cancer perception and screening behavior. [19] In-clinic screening outcomes for participants, including completion of in-clinic screening and pathology results were collected.

Of 4,256 people who contacted the study to participate in MBMT3, 2,771 (65%) did not meet inclusion criteria and 587 (14%) did not fully complete eligibility screening, resulting in 898 PWC who were determined to be study eligible. Of those, 790 (88%) completed the baseline survey, of which 30 (3.3%) were excluded after being found screening ineligible post-randomization (n=22) or to the trial being halted due to the COVID-19 pandemic (n=8). This left a total of 760 PWC included for baseline analyses, of which 461 were randomly assigned to the intervention arm and included in this analysis.

Statistical Analysis

Self-collected hrHPV results are reported as positive or negative. HrHPV-positive tests are further categorized as positive for types 16, 18/45, or non-16/18/45. Descriptive statistics were used to describe clinic follow-up rates. Bivariate and multivariate logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for associations between baseline demographic characteristics and hrHPV-positivity. We used independent groups t-tests to assess differences in attitudes toward cervical cancer and screening responses between hrHPV-positive and -negative groups.

RESULTS

Of 461 participants assigned to the intervention arm (self-collection) of the MBMT-3 RCT, 377 received mailed HPV self-collection kits (those who did not receive kits were due to ineligibility after randomization, COVID-19 pandemic related issues and incorrect mailing address or contact number). 341 (90.5%) returned cervico-vaginal samples for hrHPV testing and 329 had valid results. The median age of participants was 42 years and the median time since last Pap smear was 5 years (Table 1). Most participants were uninsured (78%), with a median annual household income of $15,000 and about half (49%) received some form of social assistance. Almost half (41%) reported having a history of abnormal Pap smear(s). Participants self-identified as non-Hispanic Black (46%), non-Hispanic White (43%), Hispanic or Latina (4%) and other (5%). Most lived in urban areas (92%) and with a high proportion (41%) who are current smokers. Most (60%) reported age of first sexual intercourse as ≥16 and the median number of sexual partners in the past year was 1 (range 0-3).

Table 1:

Participant characteristics of 329^* under-screened people with a cervix in North Carolina

Characteristics	n (%)
Median age in years (range)	42 (25-63)
Median time since last Pap smear in years (range)	5 (4-25)
Never had a Pap smear	12 (4%)
Median age of those who never had Pap smear in years (range)	27 (25-56)
History of abnormal Pap result(s)	134 (42%)†
Health insurance
Uninsured	259 (78%)
Insured (Medicaid/Medicare)	70 (21%)
Median annual household income (range)	$15000 ($0-$60000)
Receives social assistance‡	162 (49%)
Lived in urban area (vs. rural)**	302 (92%)
Race/ethnicity††
White, non-Hispanic or Latina	143 (43%)
Black, non-Hispanic or Latina	151 (46%)
Hispanic or Latina	13 (4%)
Other‡‡	18 (5%)
Marital Status
Single / Never married	153 (47%)
Married / Living with partner	81 (25%)
Divorced / Separated / Widowed	92 (28%)
Education
High school diploma, GED§§or less	138 (42%)
Sexual Orientation
Heterosexual	299 (91%)
Gay/Lesbian or Bisexual	28 (9%)
Age of first intercourse ≥16 years old	199 (60%)
Median number of sexual partners in the last year (range)	1 (0-3)
Current smoker	136 (41%)

^*Totals may not add up to full sample size due to missing data

^†This percentage is out of the 317 reported ever having a Pap test before

^‡Includes food stamps, housing assistance, welfare payments, social security, supplemental security income, disability payments.

^**Derived from 2006 Rural-Urban Commuting Area (RUCA) codes

^††Hispanic identification based on participant response to question “are you Hispanic or Latina?” Followed by “what is your race or ethnicity?” with self-classification options for “White,” “Black or African American” etc.

^‡‡Other races include those who identified as Asian (n=3), American Indian or Alaska Native (n=3) and more than one of the following: American Indian, Asian, Pacific Islander, black/African American and White (n=12).

^§§GED=General Education Development or Diploma

The overall prevalence of hrHPV was 16% (n=52) (Table 2). Type-prevalence of hrHPV type 16 was 1.2% (n=4) and types 18/45 was 1.5% (n=5, Table 2). Of 52 hrHPV-positive participants, 24 (46%) presented to clinic for cervical cancer screening, compared to 56 (20%) of 277 hrHPV-negative participants. Pap cytology results for these 24 hrHPV-positive participants included 17 negative for intraepithelial lesions (NILM), five atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (ASCUS/LSIL) and two high grade squamous intraepithelial lesion (HSIL). One participant with ASCUS Pap had a clinic co-test positive for HPV-18/45, and therefore underwent colposcopy evaluation per screening guidelines. [14] Work-up ultimately revealed CIN2 on cervical biopsy and this participant underwent Loop Electrosurgical Excision Procedure (LEEP) with a final pathology of CIN2. The 2 participants with HSIL also underwent colposcopy evaluation with the following findings: The first had a clinic co-test positive for HPV-16 & 18/45 and high grade squamous intraepithelial lesion (HSIL) on Pap, ultimately with benign pathology on cervical biopsy. The second had a clinic co-test positive for hrHPV (non-16/18/45), HSIL on Pap, CIN3 on biopsy, and subsequently underwent LEEP with a final pathology of CIN2/3.

Table 2:

Bivariate and multivariate analysis of characteristics associated with high-risk HPV (hrHPV) detection on home self-collection in under-screened women in North Carolina.

Characteristics	Total	hrHPV pos n (% positive)	Crude OR (95% CI)	Adjusted OR (95% CI)*
Total	329†	52 (16%)§§	-	-
Age
24-34 years	91	17 (19%)	1.38 (0.64-3.00)	-
35-49 years	142	21 (15%)	1.03 (0.50-2.14)	-
50-65 years	97	14 (14%)	REF	-
Time since last Pap smear (years)‡
4-5 years ago	157	23 (15%)	REF	-
6 or more years ago / Never had a Pap	151	28 (19%)	1.31 (0.72-2.41)	-
Don’t know	22	1 (5%)	-	-
Has a history of abnormal Pap smear(s)‡
No	167	25 (15%)	REF	-
Yes	135	22 (16%)	1.12 (0.60-2.08)	-
Don’t know	2	1 (50%)	-	-
Health insurance
Insured (Medicaid/Medicare)	70	13 (19%)	REF	-
Uninsured	260	39 (15%)	1.23 (0.64-2.57)	-
Income, annual household
$0-$9,999	103	22 (21%)	2.32(1.01-5.36)	1.93 (0.82-4.56)
$10,000-$24,999	126	20 (16%)	1.61 (0.70-3.74)	1.59 (0.67-3.63)
≥$25,000	87	9 (10%)	REF	REF
Race/ethnicity§
Non-Hispanic white	143	20 (40%)	REF	-
Non-Hispanic black	152	25 (16%)	1.22 (0.64-2.31)	-
Hispanic	13	2 (15%)	1.12 (0.23-5.42)	-
Other**	18	5 (28%)	2.37 (0.76-7.36)	-
Marital status
Married or living with partner	81	11 (14%)	REF	-
Single or never married	154	24 (16%)	1.18 (0.56-2.56)	-
Divorced, separated or widowed	92	17 (18%)	1.44 (0.63-3.29)	-
Sexual orientation
Heterosexual	300	47 (16%)	REF	-
Gay/Lesbian or Bisexual	28	5 (18%)	1.17 (0.42-3.22)	-
Age of first sexual intercourse
Never had sex	2	0	-	-
<16 years	126	18 (14%)	REF	-
≥16 years	199	33 (17%)	1.20 (0.64-2.24)	-
Number of sexual partners in the last year
Never had sex	2	0	-	-
0-1 partner	250	33 (13%)	REF	REF
2 or more partners	74	18 (24%)	2.15 (1.13-4.11)	2.00 (1.03-3.88)
Current smoking
Non-smoker	189	24 (13%)	REF	-
Smoker	137	28 (20%)	1.78 (0.98-3.23)	-

^*Adjusted for Income, annual household and number of sexual partners in the last year

^†Totals may not add up to full sample size due to missing data

^‡26 reported not having had a Pap smear in the past

^§Hispanic identification based on participant response to question “are you Hispanic or Latina?” Followed by “what is your race or ethnicity?” with self-classification options for “White,” “Black or African American” etc

^**Other races include those who identified as Asian (n=3), American Indian or Alaska Native (n=3) and more than one of the following: American Indian, Asian, Pacific Islander, black/African American and White (n=12).

^§§Prevalence of HPV type 16 was 1.2% (n=4), HPV type 18/45 was 1.5% (n=5) and hrHPV non-16/18/45 was 13% (n=42). 1 invalid genotyping result

In bivariate analyses (Table 2), two risk factors for hrHPV-positivity on self-collection were identified: annual household income less than $10,000 (crude OR (cOR)=2.32, 95% CI: 1.01-5.36 versus $25,000 or greater) and having ≥2 sexual partners in the past year (cOR=2.15, 95% CI: 1.13-4.11 versus ≤1 sexual partner). When both factors were adjusted for in the multivariate analysis, having ≥2 partners in the last year remained a risk factor with adjust OR (aOR) of 2.00 (95% CI: 1.03-3.88).

Comparing attitudes towards cervical cancer and screening, hrHPV-positive individuals were more likely to agree with the statement “I have almost no chance of getting cervical cancer” than those who screened negative (mean ± SD: 2.2 ± 1.1 and 1.9± 1.0, respectively; p=0.02, Table 3). In both groups, majority responded that they were more likely to go the doctor only when sick (78% for hrHPV-positive and 78% for hrHPV-negatives), felt they were at risk of cervical cancer (59%, 75%), felt that getting cervical cancer would affect their lives (92%, 87%) and did not think there was a promiscuity stigma to cervical cancer (94%, 88%) (Figure 1). In terms of screening attitudes, most participants in both groups felt strongly that screening can lower the chances of getting cervical cancer (62%, 67%) and almost all participants thought it is important to get regular screening (100%, 97%). Perceived barriers identified by both groups were that cervical cancer screening was not affordable (80%, 76%) and that clinics hours are not accessible (72%, 61%). Neither group identified being too busy (18%, 20%) as significant barriers to screening.

Table 3:

Perceptions of and attitudes towards cervical cancer and screening stratified by high-risk HPV (hrHPV) detection on home self-collection.

Behavioral Questions	hrHPV-positive Mean ± SD*	hrHPV-negative Mean ± SD*	p-value†
Healthcare utilization
I go to the doctor only when I am sick	3.3 ± 1.1	3.2 ± 1.0	0.80
Perceived risk of cervical cancer
I have almost no chance of getting cervical cancer	2.2 ± 1.1	1.9 ± 1.0	0.02‡
If I got cervical cancer, it would affect my life§	1.4 ± 0.7	1.4 ± 0.8	0.59
Perception of cervical cancer
If I had cervical cancer, people would think I slept around	1.5 ± 1.0	1.4 ± 0.8	0.16
Attitudes towards cervical cancer screening
Getting screened will lower my chances of getting cervical cancer	2.8 ± 1.3	3.0 ± 1.2	0.55
It is important to get regular cervical cancer screening	3.9 ± 0.3	3.8 ± 0.6	0.30
Perceived barriers to cervical cancer screening
If I needed to get cervical cancer screening, it would cost more than I can pay	3.3 ± 1.1	3.1 ± 1.1	0.22
I am too busy to go for cervical cancer screening	1.5 ± 1.0	1.6 ± 1.0	0.51
Clinics where I can get cervical cancer screening are only open when I can’t go	3.0 ± 1.3	2.7 ± 1.4	0.15

^*Mean of 4 point response-scale answers coded as 4 (strongly agree), 3 (somewhat agree), 2 (somewhat disagree) and 1 (strongly disagree).

^†Student’s t-test used to calculate p-value

^‡statistically significant at p < 0.05

^§Original question: If you get cervical cancer, how much would it affect your life? 1=not at all, 2=a little, 3=moderate amount, 4=a lot

Figure 1.

Association of attitudes towards cervical cancer and screening and home high-risk HPV (hrHPV) self-collection result. (hrHPV negative n=277, hrHPV positive n=52).

*p<.05

‡Original question was “If you get cervical cancer, how much would it affect your life?” with answer choices of: 1=not at all, 2=a little, 3=moderate amount, 4=a lot.

DISCUSSION

Cervical cancer is preventable when caught early and self-collection for hrHPV testing is a promising screening tool. Among low-income PWC who were largely uninsured, the hrHPV RNA prevalence in self-collected samples was 16% and having ≥2 sexual partners in the past year was associated with increased risk of hrHPV infection. Follow-up in-clinic attendance for cervical cancer screening was higher for hrHPV-positive than hrHPV-negative participants, however the two groups appeared to have similar attitudes and beliefs about cervical cancer and screening, with the exception that hrHPV-positive participants reported a lower perceived risk of cervical cancer.

The 16% hrHPV prevalence rate by RNA assay found among rarely-screened PWC is consistent with our prior pilot studies in NC that found a 12% hrHPV prevalence by Aptima RNA detection [8] and 15% by DNA detection. [7] While studies of hrHPV prevalence in underscreened populations in the US are rare and predominantly utilize DNA assays, our observed hrHPV RNA prevalence was similar. [20, 21] For example, a hrHPV DNA prevalence rate of 16.6% was detected among participants in Appalachian Virginia with similar demographic characteristics as those participating in our study (56% smokers and 44% receiving social assistance) [21] and 19% among underscreened among women who self-identified as Hispanic, Black or Haitian in Florida. [11] However, a relatively higher hrHPV prevalence with self-collected samples was reported in underscreened populations in Appalachian Ohio among predominantly insured population (26% by DNA assay), [22] and in the Mississippi Delta (27% by DNA assay). [23]

When comparing RNA and DNA assays for HPV detection, it is important to note that RNA tests have a relatively higher specificity than DNA tests for CIN2+ detection, which can contribute to a lower overall hrHPV detection rate. [16,17] HrHPV types 16, 18 and 45 together account for over 75% of squamous cell carcinoma and 94% of adenocarcinoma. [24] Our observed prevalence of hrHPV types 16 and 18/45 together was 2.7%, comparable to a U.S. 2007 population-based prevalence of 3.4% for HPV 16/18 by self-collection using a DNA assay. [25]

Less than half of hrHPV-positive participants (46%) presented to clinic, despite receiving a strong recommendations from our study staff to seek in-clinic screening. While in-clinic screening completion could be an underestimate given that some participants may have presented to non-study affiliated clinics, it highlights the ongoing challenge of ensuring follow-up for participants with HPV-positive self-collection results. However, our observed in-clinic screening attendance of hrHPV-positive participants was notably higher than those with hrHPV-negative results (20%). These results are similar to those in Appalachian Ohio, US, where Pap test attendance was higher in women with positive self-collection HPV results (33%) compared to negative (7%), [22]. The stronger message to attend screening provided to PWC with hrHPV positive results may have contributed to the higher observed in-clinic screening uptake than hrHPV negative participants. However, it is also possible that HPV-positive home-screening with result-specific counseling can serve as a motivation for in-clinic screening attendance.

While participants reported a relatively low number of sexual partners (median=1), those who reported having multiple sexual partners (≥2) in the last year had a 2-fold increased risk of hrHPV infection, consistent with well-established literature. [26] Studies have shown that both lifetime and recent sexual partners are positively associated with hrHPV detection in PWC in clinic [28] and self-collected samples. [10, 11] Younger age of first sexual intercourse has also been shown to increase the risk of acquiring hrHPV infection, [26,27] however this was not seen in our sample. We also expected to find associations of hrHPV risk with younger age, current smoker and history of abnormal Pap as reported in prior studies, [10, 28] however while we observed trends consistent with literature, our estimates were relatively imprecise, thus limiting interpretation.

As suggested by the Health Belief Model, attitudes regarding a disease and a screening process can affect an individual’s motivation for screening. [29] HrHPV-positive PWC appeared to have a lower perceived risk of getting cervical cancer than their hrHPV-negative peers. This is consistent with the idea that low perceived risk can be associated with increased engagement in at-risk behaviors. [29] No other differences in attitudes towards screening were found between the groups. And overall, participants’ responses were consistent with positive screening behavior, such as perceiving self-risk for the disease and belief that screening is important. However, most participants said they only went to the doctor when sick, reflecting a healthcare-seeking attitude that could contribute to non-participation in clinic screening in this cohort. Lastly, cost was reported by most participants as a barrier to screening. This may be attributed to the characteristics of our target population, as all participants were low-income and predominantly uninsured.

One clear strength of our study is the focus on under-insured and low-income PWC who represent a population not typically captured in healthcare-based cohorts, but who would benefit most from accessible interventions such as mailed home HPV self-collection kits. This study also benefited from having both behavioral and clinical information, which allows a more in-depth evaluation of predictors of hrHPV positivity, increases understanding of our target population and guides responsive interventions to increase screening uptake.

Limitations of this study include the cross-sectional design, which cannot support causal inference about the temporal relationship between identified risk factors and hrHPV infection. This assessment only measures current infection and does not indicate past exposure to HPV. As such, hrHPV prevalence may underestimate cumulative incidence as many infections clear. Our sample size may have limited power to detect associations between some risk factors and hrHPV-positivity, notably for less common factors with relatively small sample sizes.

In conclusion, among a population of underscreened PWC, we found a relatively high hrHPV RNA prevalence, and rather low in-clinic follow-up among participants with primary HPV screen-positive results. Efforts to reach underscreened PWC is critical in cervical cancer prevention and home self-collection kits for hrHPV testing is a promising modality. Though at present, HPV self-collection of cervico-vaginal cells is not yet FDA approved in the US, HPV self-collection is being used in several national screening programs in Europe [30] based on substantive evidence on the there is growing evidence validity of self-collection for detection of high-grade cervical precancer. [4] Future studies aimed at home self-collection should address methods of increasing follow-up clinic attendance for those with hrHPV positive self-collection results.