Randomized Trial of In-Home Cervical Cancer Screening in Underscreened Women

• ClinicalTrials.gov Identifier: NCT02005510
• Recruitment Status: Completed
• First Posted: December 9, 2013
• Results First Posted: September 16, 2020
• Last Update Posted: September 16, 2020
• Sponsor: University of Washington
• Collaborators: Kaiser Permanente; University of Texas Southwestern Medical Center; National Cancer Institute (NCI); University of California, Davis
• Information provided by (Responsible Party): Rachel Winer, University of Washington

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Investigator); Primary Purpose: Screening
• Condition: Cervical Cancer
• Interventions: Behavioral: Mailed in-home high-risk HPV testing kit; Other: Usual care
• Enrollment: 19851

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	In-home HPV Screening	Usual Care
Arm/Group Description	Usual care PLUS a mailed in-home high-risk HPV testing kit (accompanied by an invitational letter, research information sheet, and illustrated instructions for using the kit). "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Mailed in-home high-risk HPV testing kit Usual care	Usual care. "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Usual care
Period Title: Randomized (Round 1)
Started	8120 [1]	8111 [2]
Completed	8120	8111
Not Completed	0	0
[1] Excludes 163 determined to be ineligible post-randomization due to delays in data warehouse update.; [2] Excludes 196 determined to be ineligible post-randomization due to delays in data warehouse update.
Period Title: Rerandomized (Round 2)
Started	1631 [1]	1585 [2]
Completed	1631	1585
Not Completed	0	0
[1] Excludes 10 determined to be ineligible post-randomization due to delays in data warehouse update.; [2] Excludes 5 determined to be ineligible post-randomization due to delays in data warehouse update.
Period Title: Rerandomized (Round 3)
Started	209 [1]	195
Completed	209	195
Not Completed	0	0
[1] Excludes 5 determined to be ineligible post-randomization due to delays in data warehouse update.

Baseline Characteristics

Arm/Group Title		In-home HPV Screening	Usual Care	Total
Arm/Group Description		Usual care PLUS a mailed in-home high-risk HPV testing kit (accompanied by an invitational letter, research information sheet, and illustrated instructions for using the kit). "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Mailed in-home high-risk HPV testing kit Usual care	Usual care. "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Usual care	Total of all reporting groups
Overall Number of Baseline Participants		9843	9891	19734
Baseline Analysis Population Description		Baseline characteristics are not available for 117 participants in the intervention arm who opted out of electronic medical record review.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	9843 participants	9891 participants	19734 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	9843 100.0%	9891 100.0%	19734 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	9843 participants	9891 participants	19734 participants
	Female	9843 100.0%	9891 100.0%	19734 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	9843 participants	9891 participants	19734 participants
	Hispanic or Latino	486 4.9%	8761 88.6%	9247 46.9%
	Not Hispanic or Latino	8710 88.5%	480 4.9%	9190 46.6%
	Unknown or Not Reported	647 6.6%	650 6.6%	1297 6.6%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	9843 participants	9891 participants	19734 participants
	American Indian or Alaska Native	147 1.5%	145 1.5%	292 1.5%
	Asian	893 9.1%	880 8.9%	1773 9.0%
	Native Hawaiian or Other Pacific Islander	151 1.5%	139 1.4%	290 1.5%
	Black or African American	438 4.4%	431 4.4%	869 4.4%
	White	7018 71.3%	7111 71.9%	14129 71.6%
	More than one race	285 2.9%	283 2.9%	568 2.9%
	Unknown or Not Reported	911 9.3%	902 9.1%	1813 9.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	9843 participants	9891 participants	19734 participants
		9843	9891	19734

Outcome Measures

1. Primary Outcome

Title	Number of Participants Diagnosed With Cervical Epithelial Neoplasia Grade 2 or Worse
Description	Histologic diagnosis of cervical intraepithelial neoplasia grade 2 or worse
Time Frame	Assessed for up to 12 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	In-home HPV Screening	Usual Care
Arm/Group Description:	Usual care PLUS a mailed in-home high-risk HPV testing kit (accompanied by an invitational letter, research information sheet, and illustrated instructions for using the kit). "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Mailed in-home high-risk HPV testing kit Usual care	Usual care. "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Usual care
Overall Number of Participants Analyzed	9960	9891
Measure Type: Count of Participants; Unit of Measure: Participants
	12 0.1%	8 0.1%

2. Primary Outcome

Title	Number of Participants That Received Treatment for Cervical Intraepithelial Neoplasia Grade 2 or Worse
Description	Receipt of treatment for cervical intraepithelial neoplasia grade 2 or worse
Time Frame	Assessed for up to 18 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	In-home HPV Screening	Usual Care
Arm/Group Description:	Usual care PLUS a mailed in-home high-risk HPV testing kit (accompanied by an invitational letter, research information sheet, and illustrated instructions for using the kit). "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Mailed in-home high-risk HPV testing kit Usual care	Usual care. "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Usual care
Overall Number of Participants Analyzed	9960	9891
Measure Type: Count of Participants; Unit of Measure: Participants
	12 0.1%	7 0.1%

3. Secondary Outcome

Title	Number of Participants That Completed Uptake of Cervical Cancer Screening
Description	Uptake of cervical cancer screening is defined as either: [1] receipt of a Pap or co-test; [2] self-sample hrHPV-positive (16/18-negative) OR unsatisfactory AND receipt of follow-up diagnostic testing (Pap or co-test or colposcopy); [3] self-sample HPV16/18-positive; or [4] self-sample hrHPV-negative) Using an intent-to-treat approach, we will use log-binomial regression to estimate the relative risk for cervical cancer screening uptake for the in-home HPV screening arm versus the usual care arm. We will also use log-binomial regression to estimate the effects of EMR-derived patient characteristics (e.g. age, race/ethnicity, geocoded socioeconomic status, geocoded distance form primary care clinic, insurance type, time since last Pap test, tobacco use, obesity, and Charlson comorbidity score) on cervical cancer screening uptake, stratified subdivided by randomization arm.
Time Frame	Assessed for up to 6 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	In-home HPV Screening	Usual Care
Arm/Group Description:	Usual care PLUS a mailed in-home high-risk HPV testing kit (accompanied by an invitational letter, research information sheet, and illustrated instructions for using the kit). "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Mailed in-home high-risk HPV testing kit Usual care	Usual care. "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Usual care
Overall Number of Participants Analyzed	9960	9891
Measure Type: Count of Participants; Unit of Measure: Participants
	2618 26.3%	1719 17.4%

4. Secondary Outcome

Title	Number of Participants With an Abnormal Screening Result
Description	Screening result that warrants repeat testing, surveillance, or immediate colposcopy (per current guidelines) before returning to a routine screening schedule Using an intent-to-treat approach, we will use log-binomial regression to estimate the relative risk for an abnormal screening result for the in-home HPV screening arm versus the usual care arm.
Time Frame	Assessed for up to 6 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	In-home HPV Screening	Usual Care
Arm/Group Description:	Usual care PLUS a mailed in-home high-risk HPV testing kit (accompanied by an invitational letter, research information sheet, and illustrated instructions for using the kit). "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Mailed in-home high-risk HPV testing kit Usual care	Usual care. "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Usual care
Overall Number of Participants Analyzed	9960	9891
Measure Type: Count of Participants; Unit of Measure: Participants
	225 2.3%	114 1.2%

5. Secondary Outcome

Title	Experiences and Attitudes Associated With In-home HPV Testing Uptake
Description	Experiences and attitudes will be measured with online surveys. A subset of intervention arm participants who do and do not return the in-home HPV kit will be invited to complete a survey (target n=200). We will examine psychosocial factors (e.g., cervical cancer/HPV knowledge, attitudes toward screening), experiences, and reactions to kits. We will compare responses in women who do versus do not return a mailed HPV kit.
Time Frame	Survey invitation mailed 6 months post-randomization

Outcome Measure Data

Analysis Population Description

A subset of intervention arm participants who do and do not return the in-home HPV kit will be invited to complete a survey.

Arm/Group Title	In-home HPV Screening	Usual Care
Arm/Group Description:	Usual care PLUS a mailed in-home high-risk HPV testing kit (accompanied by an invitational letter, research information sheet, and illustrated instructions for using the kit). "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Mailed in-home high-risk HPV testing kit Usual care	Usual care. "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Usual care
Overall Number of Participants Analyzed	1355	0
Measure Type: Count of Participants; Unit of Measure: Participants
Kit returner and responded	116 8.6%
Kit returner and did not respond	156 11.5%
Kit non-returner and responded	119 8.8%
Kit non-returner and did not respond	964 71.1%

6. Secondary Outcome

Title	Experiences and Attitudes Associated With Follow-up of Positive In-home HPV Testing Results
Description	Intervention arm participants who return in-home HPV kits and test positive for HPV will be invited to complete an in-depth semi-structured interview (target n=50). We will explore patient perspectives following a positive human papillomavirus (HPV) self-sampling result to describe experiences and information needs for this home-based screening modality.
Time Frame	Interview invitation mailed after all recommended clinical follow-up complete OR study follow-up window complete, up to 12 months post-randomization

Outcome Measure Data

Analysis Population Description

Intervention arm participants who return in-home HPV kits and test positive for HPV will be invited to complete an in-depth semi-structured interview.

Arm/Group Title	In-home HPV Screening	Usual Care
Arm/Group Description:	Usual care PLUS a mailed in-home high-risk HPV testing kit (accompanied by an invitational letter, research information sheet, and illustrated instructions for using the kit). "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Mailed in-home high-risk HPV testing kit Usual care	Usual care. "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Usual care
Overall Number of Participants Analyzed	75	0
Measure Type: Count of Participants; Unit of Measure: Participants
Kit HPV positive and interviewed	46 61.3%
Kit HPV positive and not-interviewed	29 38.7%

Adverse Events

Time Frame	Up to 6 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	In-home HPV Screening		Usual Care
Arm/Group Description	Usual care PLUS a mailed in-home high-risk HPV testing kit (accompanied by an invitational letter, research information sheet, and illustrated instructions for using the kit). "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Mailed in-home high-risk HPV testing kit Usual care		Usual care. "Usual care" consists of patient-, provider-, clinic- and systems-level services to promote adherence to Pap screening, including an annual birthday letter with Pap screening reminders, telephone outreach from primary care providers, and automatic alerts in the electronic medical record for overdue women. Usual care
All-Cause Mortality
	In-home HPV Screening		Usual Care
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/9960 (0.00%)		0/9891 (0.00%)
Serious Adverse Events
	In-home HPV Screening		Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9960 (0.00%)		0/9891 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	In-home HPV Screening		Usual Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/9960 (0.05%)		0/9891 (0.00%)
General disorders
Light bleeding *	2/9960 (0.02%)	2	0/9891 (0.00%)	0
Discomfort *	3/9960 (0.03%)	3	0/9891 (0.00%)	0
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Rachel Winer
• Organization: University of Washington
• Phone: 2066165081
• EMail: rlw@uw.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Winer RL, Lin J, Tiro JA, Miglioretti DL, Beatty T, Gao H, Kimbel K, Thayer C, Buist DSM. Effect of Mailed Human Papillomavirus Test Kits vs Usual Care Reminders on Cervical Cancer Screening Uptake, Precancer Detection, and Treatment: A Randomized Clinical Trial. JAMA Netw Open. 2019 Nov 1;2(11):e1914729. doi: 10.1001/jamanetworkopen.2019.14729.

• Responsible Party: Rachel Winer, University of Washington
• ClinicalTrials.gov Identifier: NCT02005510
• Other Study ID Numbers: 44731; R01CA168598 ( U.S. NIH Grant/Contract )
• First Submitted: December 3, 2013
• First Posted: December 9, 2013
• Results First Submitted: January 20, 2020
• Results First Posted: September 16, 2020
• Last Update Posted: September 16, 2020