Diagnostic Accuracy of the Daye Diagnostic Tampon Compared to Clinician-Collected and Self-Collected Vaginal Swabs for Detecting HPV: A Comparative Study

Diagnostic Accuracy of the Daye Diagnostic Tampon Compared to Clinician-Collected and Self-Collected Vaginal Swabs for Detecting HPV: A Comparative Study | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Diagnostic Accuracy of the Daye Diagnostic Tampon Compared to Clinician-Collected and Self-Collected Vaginal Swabs for Detecting HPV: A Comparative Study Valentina Milanova , Michelle Gomes , Kalina Mihaylova , John Luke Twelves , Jan Multmeier , Hana McMahon , View ORCID Profile Hannah McCulloch , Kate Cuschieri doi: https://doi.org/10.1101/2024.12.02.24318200 Valentina Milanova 1 Daye , London, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site Michelle Gomes 1 Daye , London, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: michelle.gomes{at}yourdaye.com Kalina Mihaylova 1 Daye , London, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site John Luke Twelves 2 Lindus Health , London, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jan Multmeier 3 TotalEffects GmbH , Oranienburg, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site Hana McMahon 4 University of Edinburgh , Scotland, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site Hannah McCulloch 5 Independent consultant , London, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Hannah McCulloch Kate Cuschieri 4 University of Edinburgh , Scotland, United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abstract Full Text Info/History Metrics Data/Code Preview PDF Abstract Introduction Cervical cancer screening is vital for achieving global elimination of this preventable disease. Vaginal self-sampling (VSS) for human papillomavirus (HPV) has the potential to increase screening uptake, particularly among individuals who may be underserved by clinician collection. Expanding self-sampling options with accurate, acceptable collection devices is essential. The Daye Diagnostic Tampon (DDT) offers an innovative approach, utilising a menstrual tampon to collect vaginal and cervical fluid for HPV screening. This study assessed the diagnostic accuracy of the DDT in detecting high-risk HPV infections, using clinician-collected swabs (CCS) as the reference standard. Methods In this UK-based study, 260 participants provided CCS, VSS, and DDT samples for HPV testing. Samples were analysed using a clinically validated assay for 14 high-risk HPV types. Sensitivity, specificity, positive predictive value, and negative predictive value of the DDT were evaluated against CCS. Invalidity rates—HPV-negative results with negative internal controls—were compared across sampling methods. Results The DDT showed a sensitivity of 82.9% (95% CI:72.4–89.9%), specificity of 91.6% (CI:86.4–94.9%), and overall accuracy of 89.0% (CI:84.4–92.4%) relative to CCS. McNemar’s test showed no significant difference between CCS and DDT results (p = 0.845). Valid result rates were highest for DDT (99.2%), followed by VSS (95.4%) and CCS (90.8%). Conclusion The DDT demonstrates comparable accuracy to CCS for detecting high-risk HPV. This novel device shows promise as a self-sampling method. Further, complementary research should focus on assessing DDT’s clinical performance in detecting HPV associated with cervical disease endpoints. INTRODUCTION Cervical cancer is the fourth most common cancer amongst women worldwide, with an estimated 570,000 new cases and 311,000 deaths annually ( 1 ). This preventable cancer is caused by certain types of human papillomavirus (HPV). Cervical cancer screening programs are increasingly based on HPV testing, with a growing trend towards the use of self-sampling methods to identify high-risk HPV. HPV self-sampling can enhance participation rates and provides a less invasive means to engage women than traditional clinician-collected sampling (CSS) methods ( 2 – 8 ). Studies have demonstrated that self-sampling is cost-effective compared to clinician sampling, with potential cost savings due to reduced need for clinical visits and staff time, supporting its implementation as a viable option in both high-income and low- and middle-income countries ( 2 – 4 ). A randomised study by Aarnio et.al found that self-sampling for HPV testing led to higher participation rates and more cases of high-grade cervical intraepithelial neoplasia (CIN2+) detected at a significantly lower cost compared to clinician based sampling ( 5 ). Recent research in the United Kingdom (UK) found that 86% of women preferred having a choice between self-sampling and clinician sampling for cervical screenings, with 69% expressing a preference for self-sampling at home ( 8 ). The WHO have set an ambitious goal to eliminate cervical cancer by the end of the century ( 9 ). However, this target faces significant challenges. In the UK, a high income country that offers organised cervical screening, recent data show that only 68.7% of eligible individuals were adequately screened in 2021-2022, well below the 80% target ( 10 ). Additionally,iIn low and middle income countries where the majority of cancers manifest, screening programmes are often absent. To achieve the goal of cervical cancer elimination, innovative approaches to screening are urgently needed. These must address both the barriers to participation and the resource limitations within healthcare systems. Whilst vaginal self-sampling (VSS) has been shown to be an effective strategy for increasing cervical cancer screening participation, particularly among underscreened populations ( 9 ), some patients also report low self-confidence in obtaining a good quality vaginal sample with self-administered swabs, highlighting the need for more user-friendly self-sampling options ( 7 ). Menstrual tampons could offer a promising alternative for HPV sample collection due to their familiarity ( 10 ). Tampons may also have an advantage as screening tools due to their ability to remain in the vaginal canal for an extended period and their larger size compared to other options ( 11 – 12 ). Yet whilst there are several studies which have assessed the analytical and clinical performance of VSS for HPV testing ( 6 ), limited research has been conducted on the performance of menstrual tampons as a self-collection device. A systematic review and meta-analysis by Arbyn et al. highlighted the need for further research to validate the use of menstrual tampons for HPV testing ( 6 ). The Daye Diagnostic Tampon (DDT) is an innovative at-home gynaecological test kit that utilises a menstrual tampon for vaginal and cervical sample collection for high-risk HPV testing. Preliminary research has shown that self-collected tampons exhibit accuracy comparable to CCS for detecting HPV and other sexually transmitted infections ( 13 ). The present technical study builds on this preliminary data and was designed to compare the performance of the DDT to CSS for the detection of high-risk HPV; the influence of sample collection order on performance and associated comparison(s) was also assessed. METHODS Study design and setting This study employed a prospective diagnostic trial design to assess the diagnostic accuracy of the DDT compared to clinician-collected vaginal swabs (CSS) and self-collected vaginal self-swabs (VSS) for the detection of high-risk HPV. As the performance of VSS and DDT may be affected by sampling order, block randomisation was used to assign order of self-sampling with DDT or VSS. Usability and acceptability were determined through questionnaires at baseline and after sampling. To further explore acceptability, participants were offered the opportunity to participate in focus groups after trial completion. The trial was conducted in the UK between 19th December 2023 and 18th October 2024. Ethical approval was obtained from London Camberwell St Giles Ethics Committee (reference 23-LO-0882). We report against the Standards for Reporting of Diagnostic Accuracy Studies (STARD) guidelines ( 14 ). See supplementary 1 for the completed checklist. Study population The study enrolled sexually active individuals assigned female at birth (AFAB) aged 25-65 years. Participants were divided into two groups, with Group 1 consisting of individuals who had received a confirmed HPV-positive screening result within the past four weeks and could provide evidence through the trial ePRO system. All participants were required to be sexually active, defined as having penetrative vaginal sex, and willing to provide informed consent and adhere to trial procedures. Individuals were ineligible if they had undergone a previous hysterectomy or total hysterectomy with cervix removal, had known allergies or sensitivities to tampons, or had a history of Toxic Shock Syndrome (TSS). The study also excluded pregnant or breastfeeding individuals, those participating in other interventional clinical trials, and anyone using investigational drugs within the previous 30 days. Recruitment Figure 1 depicts the central recruitment flow for the trial. Participants were primarily recruited via social media. Advertising on Meta and other platforms was used to highlight the trial. Between 15th January 2024 - 16th February 2024, adverts directed potential participants to the trial website (see supplementary material 2). If interested in taking part, they completed an online pre-screening form to assess their eligibility for the trial. If potentially eligible, the Participant Information Sheet (PIS) and Informed Consent Form (ICF) were sent directly to the participant. Once enrolled, participants booked an in-person clinic appointment to see a trial nurse at a clinic. Participants self-sampled the day before their in-person clinic appointment. Participants were offered £50 to participate in the trial. Download figure Open in new tab Figure 1 Central Recruitment Flow, showing the participant flow from recruitment from patient outreach (e.g. social media, advertising to patient networks, clinic outreach to patient lists) Study procedures and sample collection Participants underwent pre-screening, informed consent, screening, and eligibility assessments online, where baseline demographic information and medical history were collected. Participants were then randomly assigned to Group A (self-swab followed by DDT) or Group B (DDT followed by self-swab) using block randomisation. Each participant received a trial kit by post, containing both the DDT and self-swab, along with sterile containers with transport medium, and detailed sampling instructions. Participants were instructed to use the DDT by inserting it into their vagina, leaving it in place for at least 20 minutes, then removing it before placement in a sterile container with 10 ml of transport medium (Copan UTM). The self-swab was also inserted vaginally and rotated before also being placed into a sterile container with 10ml of transport medium, following the manufacturer’s instructions. Sampling order was specified in the instructions, and participants were asked to allow an hour between the first and second samples. At a clinic visit the following day, participants provided their self-collected DDT and VSS samples to a nurse, and a clinician-collected vaginal swab was also obtained. After completing all samples, participants filled out additional questionnaires directly in an electronic data capture platform. Participants were offered the opportunity to participate in focus groups, to discuss their experience of using the DDT and preferences for HPV testing. The trial period lasted approximately 2-4 weeks, with all samples sent to an accredited central UK laboratory for analysis. Sample Collection Devices The swabs used for VSS and CSS were Copan FLOQSwabs® which consist of a customisable moulded plastic shaft and a tip coated with perpendicular short Nylon® fibres. Sterile containers for DDT and swab transportation contained 10 ml (DDT) and 3ml (Swab) of transport medium (Copan UTM). Diagnostic tampons used for self-sampling were sterile, 100% organic cotton, featuring a ’W’ wadding design with a protective sleeve and a bio-based polyethylene applicator ( Figure 2 ). The applicator ensures the patient can collect a sample from the cervical area, as well as from the vaginal canal. A withdrawal cord, made from mercerized organic cotton, is attached to the pledget. Download figure Open in new tab Figure 2 Structure, dimensions, and characteristics of the tampon as well as its raw materials HPV testing The Aptima® HPV assay was utilised for HPV detection. This assay targets the expression of E6/E7 mRNA of 14 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68). While the assay was performed according to manufacturer’s instructions the bio-samples used in the evaluation were not formally validated by the manufacturer; Reference and index sampling methods In this study, the gold standard or reference sampling method used was CCS, as used in many other self-sampling diagnostic accuracy studies. Our primary index sampling method of investigation was the DDT, however we also calculated the accuracy of VSS as an alternate index. As an exploratory sensitivity analysis, we also explored a collated measure of results from CCS, VSS and DDT as an alternative reference sampling method. With this collated measure, a positive result was recorded only when at least two sampling methods showed positive results. If only one of the three methods showed a positive result, the outcome was considered inconclusive. A negative result required all three samples to test negative. Statistical analyses Diagnostic accuracy parameters (sensitivity, specificity, overall accuracy, positive and negative predictive values) were calculated from all complete and conclusive results and reported with Wilson score 95% confidence intervals. Invalidity rates—HPV-negative results with negative internal controls—were compared across sampling methods. Additional sensitivity analyses were conducted. To compensate for variation in conclusive results, diagnostic accuracy parameters were repeated using the collated measure as the gold standard. McNemar tests were conducted to assess whether diagnostic accuracy differed significantly between CCS and collated results as gold standards. To understand the impact of sampling order, a sensitivity analysis was conducted assessing diagnostic accuracy for tampon swabs and self-swabs when the respective sampling method was used first vs. second. McNemar tests were conducted to compare diagnostic accuracy between DDT vs. VSS first orders for VSS and DDT, respectively. Sample size A sample size of 420 participants was calculated to provide a statistical power of 90% to test whether the sensitivity of DDT is above 70% when the assumed true sensitivity is 95% and the prevalence of HPV in the recruited patient population is 5%. This was assumed to yield 21 cases of HPV to evaluate the sensitivity of HPV. Focus groups Focus groups were held online via Google meet, a video calling platform. Participants invited to participate via email following their completion of their clinic visit. Participants were offered an additional £25 to take part in these groups. Informed consent was taken before participation. The groups were facilitated by VM and MG, with support from another facilitator (MT). The topic guide can be found in supplementary material (supplementary 3). RESULTS Sample From an initial screening of 489 participants, 437 were enrolled, with 52 screen failures. Of the 329 booked in for a clinic visit, 263 participants attended a clinic visit for CSS, having completed DDT and VSS and all questionnaires for acceptability outcomes. As three participants either did not complete CSS in clinic or had missing CSS results, the final sample used for diagnostic accuracy results consisted of 260 participants who successfully completed all study requirements, with results from all three sampling methods (CSS, VSS and DDT). In the final diagnostic accuracy sample, 26 participants had a confirmed HPV+ screening result within the previous 4 weeks (Group 1). See figure three for the participant flow chart. Download figure Open in new tab Figure 3 Participant flowchart Participant Characteristics The median age was 31.0 years, with an interquartile range between 28.0 and 36.0 years. Most participants were white (69%), heterosexual (75%), and single (59%, see Table 1 ). Characteristics of the sample used for diagnostic accuracy results (n=260), as a whole and broken down by randomisation arm, can be found in supplementary material 4, table 1 . View this table: View inline View popup Download powerpoint Table 1 Participant characteristics Diagnostic Accuracy: CSS as the gold standard A total of 780 samples (one sample per sampling method) from 260 participants were analysed. As the primary outcome, diagnostic accuracy was determined using CCS as the gold standard. For the CCS, 70 participants tested positive for HPV (26.7%) 168 participants tested negative (64.6%). For 22 participants, the test result was invalid (8.5%). Of the 22 samples that were invalid with the CCS, 21 were evaluated as positive (n = 3) or negative (n = 18) using the DDT, with 1 sample also returning an invalid result. DDT produced 2 invalid sample results, 1 of which was evaluated as negative in CCS, the other as invalid (see supplementary material 5, Table 2 ). Comparing results from VSS, 5 of the 22 invalid CCS results were also evaluated as invalid, while 14 were assessed as negative and 3 as positive for HPV. An additional 9 samples yielded invalid results in VSS ((See supplementary material 6, Table 3 ). Diagnostic accuracy metrics for both DDT and VSS vs CCS are reported in Table 2 . Using the CCS as gold standard yields a sensitivity of DDT of 82.9% (95% CI: 72.4% - 89.9%), specificity of 91.6% (86.4 % - 94.9%), PPV of 80.6% (70.0% - 88.0%), NPV of 92.7% (87.7% - 95.8%), and overall accuracy of 89.0% (84.4% - 92.4%). McNemar’s tests did not reveal a significant deviation of CCS and DTT results (χ 2 = 0.04, df = 1, p = 0.845), nor of CCS and VSS results (χ 2 = 0.03, df = 1, p = 0.860), suggesting results do not differ in terms of sensitivity and specificity. View this table: View inline View popup Download powerpoint Table 2: Diagnostic accuracy of DDT and VSS compared to CCS Sensitivity analysis: Using collated results as the gold standard The proportion of conclusive results varied between the three sampling methods – CCS yielded results in 238 samples (90.8%), DDT in 258 (99.2%), and VSS in 248 (95.4%) out of 260 samples. Therefore, as an exploratory sensitivity analysis, we explored using a collated measure as the gold standard. Using the collated results as a reference, 67 participants were classified as positive for HPV (25.8%), 178 participants were categorised as negative (68.4%), and for 2 participants, the test result was invalid (0.8%), inconclusive (n = 14, 5.4%), or missing (n = 1, 0.4%). CCS detected 62 of the 67 HPV-positive cases and 156 of the 178 HPV-negative samples (see supplementary 7, Table 4 ). Compared to the collated as a reference, CSS yielded a sensitivity of 95.4% (87.3% - 98.4%), specificity of 96.3% (92.2% - 98.3%), PPV of 91.2% (82.1% - 95.9%), NPV of 98.1% (94.6% - 99.4%), and overall accuracy of 96.0% (92.6% - 97.9%) [see table 3 ]. A McNemar’s test did not reveal a significant deviation of CCS and collated results (χ 2 = 0.44, df = 1, p = 0.504). View this table: View inline View popup Download powerpoint Table 3: Diagnostic accuracy of CCS, DDT and VSS compared to collated results as reference Using DDT as a sampling method yielded correct positive results in 62 of 67 participants categorised as HPV-positive, and correct negative results in 167 out of 176 HPV-negative participants, when using the collated measure as a reference (see supplementary 8, Table 5 ). DDT sensitivity was 92.5% (95% CI: 83.7% - 96.8%), specificity 96.0% (91.9% - 98.1%), PPV 89.9% (80.5% - 95.0%), NPV 97.1% (93.4% - 98.8%), and overall accuracy 95.0% (91.5% - 97.1%), see Table 3 . A McNemar’s test did not reveal a significant deviation of DDT and collated results (χ 2 = 0.08, df = 1, p = 0.773).For VSS, diagnostic accuracy metrics are reported in supplementary material 9, Table 6 . A McNemar’s test did also not indicate a significant deviation of VSS and collated results (χ 2 0.999). Sensitivity analysis: Sampling order Vaginal self-sampling (VVS) Sensitivity of VSS was higher when sampled first vs. second (88.9% vs. 79.3%, χ2 = 16.45, p < 0.001). See Table 4 . Specificity was slightly but significantly higher when DDT were sampled first compared to VSS first (self-swabs first: 93.3%, DDT first: 95.7%, χ2 = 57.10, p < 0.001). View this table: View inline View popup Download powerpoint Table 4: Diagnostic accuracy for VSS by sampling order Daye diagnostic tampon (DDT) For DDT, sensitivity and specificity improved significantly when DDT were sampled first vs. second (sensitivity: 100% vs. 86.5%, χ2 = 30.03, p < 0.001; specificity: 96.8% vs. 95.0%, χ2 = 65.62, p< 0.001). See Table 5 . View this table: View inline View popup Download powerpoint Table 5: Diagnostic accuracy for tampon swabs by sampling order Acceptability Questionnaire data Participant questionnaire responses (n=263) revealed high acceptance of tampon-based testing HPV. Prior to sampling, 98.5% (259/263) had used tampons, but only 29.7% (78/263) were aware of their potential for diagnostic testing. Post-sampling, tampons became the preferred testing method (46%), followed by self-swabs (33%). Comfort levels with tampon use for testing remained high (Very comfortable: 206/263, 78.3% pre-sampling; 192/263 73.0% post-sampling), and perceived ease of use increased from 63.5% (167/263) to 74.5% (196/263). While moderate or extreme concerns about accuracy slightly increased post-sampling (10.2% [27/263] to 13.6% [36/263], p < 0.05), overall acceptance remained strong. Trust in tampon results compared to clinician swabs remained stable. View this table: View inline View popup Download powerpoint Table 9. Acceptability results Focus groups Four focus groups were held with a total of 24 participants (5-7 participants in each group). Sessions lasted 60 minutes. Of the 17 unique participants who stated preferences for HPV sampling methods during focus group discussions, 12 (70.5%) shared a strong preference for DDT. Four participants held more neutral positions, sharing mixed views and preferences between DDT, VSS and visiting a clinic for sampling. One participant strongly preferred using clinic services. The participant who preferred clinic-based testing related this to their concerns about the accuracy and comfort of the DDT. Two other participants also had initial concerns about the accuracy of the DDT, despite their preference for it over other sampling methods. Other concerns raised in the group related to the convenience ( 1 ), cost ( 1 ) or sustainability ( 1 ) of the DDT, or to the clarity of information provided around self-sampling with the DDT. More extensive acceptability results from questionnaires and focus groups will be reported in a future publication. DISCUSSION The primary objective of this study was to assess the accuracy of the DDT for detecting HPV infection. We found that, when using CCS as the reference standard, DDT exhibited a sensitivity of 82.9%, specificity of 91.6%, and overall accuracy of 89.0%. DDT diagnostic performance was as good as that of VSS, which had a sensitivity of 75.4%, a specificity of 90.6% and an overall accuracy of 86.0% when compared with CSS. Results from questionnaires and focus groups suggest that tampons are an acceptable method of self-sampling for HPV, although comfort and perceived accuracy may be concerns for some. The findings of this study align with the vast body of literature that exists about the comparable accuracy of VSS vs CCS ( 15 , 16 ). A meta-analysis of six comparable studies to ours, where VSS sought to identify the presence of HPV, rather than of precancerous cell changes (CIN2+), found a pooled sensitivity of 74% (61-84%) and specificity of 88% (83- 92%), when compared to CCS ( 15 ). Limited published evidence exists on the diagnostic performance of tampons as self-sampling devices for high-risk HPV. We know of two relevant studies in South Africa which assessed the acceptability and accuracy of tampon-based self-collection for high-risk HPV testing, compared to CSS, one study with women living with HIV ( 17 ), another with gynaecology clinic attendees ( 18 ). Tampon self-sampling in Adamsnon’s study exhibited a sensitivity of 77% and specificity of 77% for detecting high-risk HPV, whilst the comparable sensitivity and specificity in Tito’s study were 86% and 88%, respectively. Unlike another older study of a different device which found tampons to have a high proportion of insufficient quality specimens ( 19 ), the DDT only yielded 0.8% (2/260) invalid results, when compared to CSS results. We found the DDT to be an acceptable method for HPV self-sampling. This echoes the few other UK-based and global studies conducted, which have found it to be an acceptable, convenient and easy to use option ( 17 , 18 , 20 ). Though potentially a more supportive sample, a study in London (n=501) where women were recruited from colposcopy units, found the majority of participants (98%) approved of tampons being used as a self-collection tool to test for HPV infection ( 20 ). The above-mentioned South African studies also reported high levels of acceptability. Adamson’s study of women living with HIV (n=325) found that over 90% of participants reported no difficulties in collecting HPV samples with a tampon, and 82% were willing to self-collect with a tampon at home ( 17 ). Another study in South Africa (n=527) found very similar results showing self-sampling with a tampon to be a comfortable, painless option, preferable for many ( 18 ). Sensitivity analyses showed that the diagnostic performance of the DDT increased to a sensitivity of 92.5% (83.7 – 96.8), a specificity of 96.0% (91.9 – 98.1) and an overall accuracy of 95.0% (91.5 – 97.1) when using the collated measure as the reference standard, rather than CCS. We conducted the sensitivity analysis with a collated measure to mitigate against solely relying on the CCS given that it produced the highest invalidity rate. We suspect that the robustness of CSS in our study is limited by the fact that the copan swab used for both clinician and self collection is not formally approved for use for APTIMA testing. As the APTIMA HPV test used does not include an endogenous cellular control, invalidity was driven by other reasons beyond a lack of available cellular material which likely included inhibition. The novel approach of using a composite measure leverages all available information and mitigates against the high invalidity rate from CSS alone. Notably, DDT and CCS performed very similarly when using the collated results. Sensitivity analyses also suggest that sampling order may have had an impact on DDT’s diagnostic performance. The analysis of sampling order revealed significant effects of the order of sampling on diagnostic accuracy for VSS and DDT. Sensitivity increased for both methods when sampled first, which is consistent with expectation and published evidence. Specificity decreased slightly (but significantly) for VSS when the VSS was sampled first; interestingly, specificity was increased when the DDT was taken first. Reasons for the specificity observations are not entirely clear; whilst the dimensions and absorbency of the different devices are likely to play a role, these data underline the importance of the evaluation and validation of individual devices. Study strengths and limitations This is a timely study of an innovative device that could broaden choice within HPV self-sampling ( 9 – 10 ). It is important to note the contribution this study makes to a gap in evidence, as there are limited data on the acceptability and performance of tampons as biospecimens for HPV testing, in particular where the impact of sampling order is assessed ( 17 , 18 , 20 ). Consequently, we hope these data act as a grounding for further development and evaluation of the DDT. Some limitations should be considered. We experienced greater loss to follow up than anticipated, resulting in a smaller sample than planned of 260. However, due to targeted recruitment of those with a confirmed HPV result, which enriched our population, we superseded the required number of cases to confidently evaluate the DDT sensitivity if greater than 70%, compared to CSS. In this study, we only used one HPV assay; further work could enhance findings by evaluating other DDT and HPV assay combinations, increasing reliability. As mentioned, despite being the commonly referenced gold-standard, CCS produced the highest invalidity rate amongst the three sampling methods. To mitigate against this, we conducted a sensitivity analysis with a collated measure, leveraging all available results. Most importantly, we recognize that our assessment focused on diagnostic accuracy for HPV detection, rather than HPV associated with histologically confirmed disease, specifically CIN2+. The absence of follow-up limits our ability to assess the sampling methods’ longitudinal performance ( 21 ). To address this, ongoing work is evaluating the clinical performance of the DDT relative to CIN2+, which will naturally extend the data presented here. Additionally, it is crucial to assess the effectiveness of DDT in diverse populations, considering various age groups, ethnicities, and socioeconomic backgrounds, to ensure broad applicability and address potential confounding factors ( 22 ). Whilst we did achieve a diverse sample in terms of ethnicity and sexuality, which is of particular importance due to lower screening in these groups ( 23 , 24 ) , future studies could be repeated with older participants. This is particularly important given that cervical cancer screening programmes in the UK suggest screening until women and individuals AFAB reach 64-years-old ( 25 ). Conclusion This study confirms the value of diagnostic tampons as an alternate method to CCS for detecting high-risk HPV infection, with high levels of diagnostic accuracy. Notably, DDT performed similarly to CCS when using the collated results as the reference standard. The performance and ease of use of DDT highlight its potential as a valuable self-collection method for cervical cancer screening. Further research is needed to validate these findings in longitudinal cohorts and relative to clinical endpoints. Understanding practical challenges and logistical considerations of DDT implementation, as well as comprehensive cost-effectiveness analyses, will help determine the financial viability of integrating DDT into screening programs, particularly in low-income countries ( 26 ). Data availability Both the full study protocol and the study data are available on reasonable request, with requests made to the corresponding author. Ethical Approval Ethical approval was obtained from London Camberwell St Giles Ethics Committee (reference 23-LO-0882). Funding This study was supported by funding from the European Innovation Council (EIC) awarded to Daye. The EIC had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflicts of interest VM is the CEO of DAYE, where MG is the Head of Global Health Policy and KM is Head of Medical Innovation. HMcC and JM were paid as consultants for DAYE; JM was also paid as a consultant for Lindus Health. HE and KC are researchers at the University of Edinburgh; HMcM received research funding from DAYE. KC’s institution has received research funding or gratis consumables to support research from the following commercial entities in the last 3 years: Abbott, Euroimmun, GeneFirst, Qiagen, Hiantis, Seegene, Roche, Hologic, Barinthus Biotherapeutics PLC & Daye. KC has attended advisory board meetings for Hologic, Becton Dickinson and Barinthus Biotherapeutics PLC (no personal remuneration received; UK travel supported for Hologic). Supplementary material Supplementary material 1. STARD checklist View this table: View inline View popup Bossuyt, P.M., Reitsma, J.B., Bruns, D.E., Gatsonis, C.A., Glasziou, P.P., Irwig, L., et al. (2015). STARD 2015: An updated list of essential items for reporting diagnostic accuracy studies Supplementary material 2. Social media recruitment adverts Download figure Open in new tab Supplementary material 3. Focus group topic guide Motivation for Joining: What motivated you to participate in the STAMP trial? What is your previous experience with HPV testing? What was your experience with the communication and logistics surrounding the trial? Experience with Collection Methods: Can you describe your experience with the self-collected tampon? Compared to the other two methods are you familiar with tampons already? Applicator vs non applicator? What challenges did you face during the sample collection process? Usability of the DT: How did you find the instructions for using the tampon? do you have experience with at home testing kits? what are your perceptions of at home testing kits? did you have any concerns about doing the self sampling yourself? What improvements would you suggest for the sample collection process with the DT? Comfort Using the DT: How comfortable were you using the tampon for sample collection? What could be done to improve your comfort level? Did you feel anxious prior to sample collection? Acceptability and Perceptions: How confident do you feel about using a tampon for sample collection in terms of accuracy? If the tampon was offered by the NHS, would you be more confident about it? Which sample collection method would you prefer for future tests? Factors that influence Would you recommend the tampon-based sampling to others? Why or why not? Supplementary material 4 View this table: View inline View popup Download powerpoint Table 1. Participant characteristics of diagnostic accuracy analyses (n=260), as a whole and by randomisation arm Supplementary material 5 View this table: View inline View popup Download powerpoint Table 2: DDT vs. CCS results Supplementary material 6 View this table: View inline View popup Download powerpoint Table 3: VSS vs. CCS results Supplementary material 7 View this table: View inline View popup Download powerpoint Table 4: CCS vs. collated results Supplementary material 8 View this table: View inline View popup Table 5: DDT vs. collated results Supplementary material 9 View this table: View inline View popup Download powerpoint Table 6: VSS vs. collated results Acknowledgements This study was made possible through the valuable contributions of Lindus Health for their excellent organisation of the clinical trial, Alderley Lighthouse Labs for their crucial lab work, and Dr. Kate Cuschieri from the University of Edinburgh for her collaboration, scientific consultation, and lab work. The authors express their deepest gratitude to these partners for their instrumental roles in successfully completing this impactful research project. Thank you to Mia Taicher for their support facilitating focus groups. Acronyms CCS Clinician-Collected Swabs CI Confidence Interval DDT Daye Diagnostic Tampon HPV Human Papillomavirus PPV Positive Predictive Value NPV Negative Predictive Value VSS Vaginal Self-Swabs References 1. ↵ Arbyn , M. , Weiderpass , E. , Bruni , L. , De Sanjosé , S. , Saraiya , M. , Ferlay , J. , et al. ( 2020 ). Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis . The Lancet Global Health , 8 ( 2 ), e191 – 203 , doi: 10.1016/ S2214-109X(19)30482-6 OpenUrl CrossRef 2. ↵ Daponte , N. , Valasoulis , G. , Michail , G. , Magaliou , I. , Daponte , A.-I. , Garas , A. , Grivea , I. , Bogdanos , D.P. , & Daponte , A . ( 2023 ). HPV-based self-sampling in cervical cancer screening: An updated review of the current evidence in the literature . Cancers , 15 ( 6 ), 1669 . doi: 10.3390/cancers15061669 OpenUrl CrossRef PubMed 3. Huntington , S. , Sudhir , K.P. , Schneider , V. , Sargent , A. , Turner , K. , Crosbie , E.J. , & Adams , E.J . ( 2023 ). Two self-sampling strategies for HPV primary cervical cancer screening compared with clinician-collected sampling: An economic evaluation . BMJ Open , 13 ( 6 ), e068940 . doi: 10.1136/bmjopen-2022-068940 OpenUrl Abstract / FREE Full Text 4. ↵ Malone , C. , Barnabas , R.V. , Buist , D.S.M. , Tiro , J.A. , & Winer , R.L . ( 2020 ). Cost-effectiveness studies of HPV self-sampling: A systematic review . Preventive Medicine , 132 , 105953 . doi: 10.1016/j.ypmed.2019.105953 OpenUrl CrossRef PubMed 5. ↵ Aarnio , R. , Östensson , E. , Olovsson , M. , et al. ( 2020 ). Cost-effectiveness analysis of repeated self-sampling for HPV testing in primary cervical screening: A randomized study . BMC Cancer , 20 , 645 . doi: 10.1186/s12885-020-07085-9 OpenUrl CrossRef PubMed 6. ↵ Arbyn , M. , Smith , S.B. , Temin , S. , Sultana , F. , & Castle , P . ( 2018 ). Detecting cervical precancer and reaching underscreened women by using HPV tests on self samples: Updated meta-analyses. BMJ , k 4823 . doi: 10.1136/bmj.k4823 OpenUrl Abstract / FREE Full Text 7. ↵ Nishimura , H. , Yeh , P.T. , Oguntade , H. , Kennedy , C.E. , & Narasimhan , M . ( 2021 ). HPV self-sampling for cervical cancer screening: A systematic review of values and preferences . BMJ Global Health , 6 ( 5 ), e003743 . OpenUrl Abstract / FREE Full Text 8. ↵ Waller , J. , Waite , F. , & Marlow , L . ( 2024 ). Awareness and knowledge about HPV and primary HPV screening among women in Great Britain: An online population-based survey . Journal of Medical Screening , 31 ( 2 ), 91 – 98 . doi: 10.1177/09691413231205965 OpenUrl CrossRef PubMed 9. ↵ Costa , S. , Verberckmoes , B. , Castle , P.E. , et al. ( 2023 ). Offering HPV self-sampling kits: An updated meta-analysis of the effectiveness of strategies to increase participation in cervical cancer screening . British Journal of Cancer , 128 , 805 – 813 . doi: 10.1038/s41416-022-02094-w OpenUrl CrossRef PubMed 10. ↵ Efficacy of self-collected diagnostic tampon as a novel tool for vaginal sample collection towards the detection of genital infections . 11. ↵ Turner , F. , Drury , J. , Hapangama , D.K. , & Tempest , N . ( 2023 ). Menstrual tampons are reliable and acceptable tools to self-collect vaginal microbiome samples . International Journal of Molecular Sciences , 24 ( 18 ), 14121 . doi: 10.3390/ijms241814121 OpenUrl CrossRef PubMed 12. ↵ Turner , F. , Drury , J. , Goodfellow , L. , Hill , C. , Baxter , H. , Milanova , V. , Drakeley , A. , Hapangama , D. , & Tempest , N . ( 2022 ). Optimising vaginal biospecimen collection . Human Reproduction , 37 (Supplement_1). doi: 10.1093/humrep/deac107.353 OpenUrl CrossRef 13. ↵ Milanova , V. , Lazarova , I. , Mihaylova , K. , et al. ( 2024 ). Efficacy and acceptability of self-collected medical grade tampon as a novel vaginal sample collection tool for the detection of HPV and STIs . Preprint (Version 1 ) available at Research Square. doi: 10.21203/rs.3.rs-3853448/v1 OpenUrl CrossRef 14. ↵ Bossuyt , P.M. , Reitsma , J.B. , Bruns , D.E. , Gatsonis , C.A. , Glasziou , P.P. , Irwig , L. , et al. ( 2015 ). STARD 2015: An updated list of essential items for reporting diagnostic accuracy studies . 15. ↵ Ogilvie , G.S. , Patrick , D.M. , Schulzer , M. , Sellors , J.W. , Petric , M. , Chambers , K. , White , R. , & FitzGerald , J.M . ( 2005 ). Diagnostic accuracy of self-collected vaginal specimens for human papillomavirus compared to clinician-collected human papillomavirus specimens: A meta-analysis . Sexually Transmitted Infections , 81 ( 3 ), 207 – 212 . doi: 10.1136/sti.2004.011858 OpenUrl Abstract / FREE Full Text 16. ↵ Petignat , P. , Faltin , D. , Bruchim , I. , Tramèr , M. , Franco , E. , & Coutlée , F . ( 2007 ). Are self-collected samples comparable to physician-collected cervical specimens for human papillomavirus DNA testing? A systematic review and meta-analysis . Gynecologic Oncology , 105 ( 2 ), 530 – 535 . OpenUrl CrossRef PubMed Web of Science 17. ↵ Adamson , P.C. , Huchko , M.J. , Moss , A.M. , Kinkel , H.F. , & Medina-Marino , A . ( 2015 ). Acceptability and accuracy of cervical cancer screening using a self-collected tampon for HPV messenger-RNA testing among HIV-infected women in South Africa . PLoS ONE , 10 ( 9 ), e0137299 . doi: 10.1371/journal.pone.0137299 OpenUrl CrossRef PubMed 18. ↵ Tiiti , T.A. , Mashishi , T.L. , Nkwinika , V.V. , Molefi , K.A. , Benoy , I. , Bogers , J. , Selabe , S.G. , & Lebelo , R.L . ( 2021 ). Evaluation of ILEX SelfCerv for detection of high-risk human papillomavirus infection in gynecology clinic attendees at a tertiary hospital in South Africa . Journal of Clinical Medicine , 10 ( 21 ), 4817 . doi: 10.3390/jcm10214817 OpenUrl CrossRef PubMed 19. ↵ McLarty , J.W. , Williams , D.L. , Loyd , S. , & Hagensee , M.E . ( 2019 ). Cervical human papillomavirus testing with two home self-collection methods compared with a standard clinically collected sampling method . Sexually Transmitted Diseases , 46 ( 10 ), 670 – 675 . doi: 10.1097/OLQ.0000000000001045 OpenUrl CrossRef PubMed 20. ↵ Khan , A.M. , Sasieni , P. , & Singer , A . ( 2015 ). A prospective double-blind cross-sectional study of the accuracy of the use of dry vaginal tampons for self-sampling of human papillomaviruses . BJOG , 122 , 388 – 394 . OpenUrl PubMed 21. ↵ Castle , P.E. , Stoler , M.H. , Wright , T.C. , Sharma , A. , Wright , T.L. , & Behrens , C.M . ( 2011 ). Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: A subanalysis of the ATHENA study . The Lancet Oncology , 12 ( 9 ), 880 – 890 . doi: 10.1016/s1470-2045(11)70188-7 OpenUrl CrossRef PubMed Web of Science 22. ↵ Bruni , L. , Diaz , M. , Barrionuevo-Rosas , L. , Herrero , R. , Bray , F. , Bosch , F.X. , et al. ( 2016 ). Global estimates of human papillomavirus vaccination coverage by region and income level: A pooled analysis . The Lancet Global Health , 4 ( 7 ), e453 – e463 . doi: 10.1016/s2214-109x(16)30099-7 OpenUrl CrossRef 23. ↵ Moser K , Patnick J , Beral V . ( 2009 ), Inequalities in reported use of breast and cervical screening in Great Britain: analysis of cross sectional survey data, BMJ , Jun 16 ; 338 : b2025 . doi: 10.1136/bmj.b2025 . OpenUrl CrossRef 24. ↵ Saunders CL , Massou E , Waller J , Meads C , Marlow LA , Usher-Smith JA . ( 2021 ) Cervical screening attendance and cervical cancer risk among women who have sex with women . J Med Screen .; 28 ( 3 ): 349 – 356 . doi: 10.1177/0969141320987271 . OpenUrl CrossRef PubMed 25. ↵ GOV.UK. (n.d.). Cervical screening: Helping you decide . Retrieved November 15, 2024, from https://www.gov.uk/government/publications/cervical-screening-description-in-brief/cervical-screening-helping-you-decide--2#:~:text=Cervical%20screening%20is%20for%20women,months%20before%20people%20turn%2025 26. ↵ Goldhaber-Fiebert , J.D. , Stout , N.K. , Salomon , J.A. , Kuntz , K.M. , & Goldie , S.J . ( 2008 ). Cost-effectiveness of cervical cancer screening with human papillomavirus DNA testing and HPV-16,18 vaccination . JNCI Journal of the National Cancer Institute , 100 ( 5 ), 308 – 320 . doi: 10.1093/jnci/djn019 OpenUrl CrossRef PubMed Web of Science View the discussion thread. Back to top Previous Next Posted December 05, 2024. Download PDF Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Diagnostic Accuracy of the Daye Diagnostic Tampon Compared to Clinician-Collected and Self-Collected Vaginal Swabs for Detecting HPV: A Comparative Study Message Subject (Your Name) has forwarded a page to you from medRxiv Message Body (Your Name) thought you would like to see this page from the medRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Diagnostic Accuracy of the Daye Diagnostic Tampon Compared to Clinician-Collected and Self-Collected Vaginal Swabs for Detecting HPV: A Comparative Study Valentina Milanova , Michelle Gomes , Kalina Mihaylova , John Luke Twelves , Jan Multmeier , Hana McMahon , Hannah McCulloch , Kate Cuschieri medRxiv 2024.12.02.24318200; doi: https://doi.org/10.1101/2024.12.02.24318200 Share This Article: Copy Citation Tools Diagnostic Accuracy of the Daye Diagnostic Tampon Compared to Clinician-Collected and Self-Collected Vaginal Swabs for Detecting HPV: A Comparative Study Valentina Milanova , Michelle Gomes , Kalina Mihaylova , John Luke Twelves , Jan Multmeier , Hana McMahon , Hannah McCulloch , Kate Cuschieri medRxiv 2024.12.02.24318200; doi: https://doi.org/10.1101/2024.12.02.24318200 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Sexual and Reproductive Health Subject Areas All Articles Addiction Medicine (573) Allergy and Immunology (865) Anesthesia (302) Cardiovascular Medicine (4453) Dentistry and Oral Medicine (444) Dermatology (383) Emergency Medicine (609) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1515) Epidemiology (15242) Forensic Medicine (30) Gastroenterology (1131) Genetic and Genomic Medicine (6615) Geriatric Medicine (669) Health Economics (1001) Health Informatics (4552) Health Policy (1372) Health Systems and Quality Improvement (1614) Hematology (543) HIV/AIDS (1270) Infectious Diseases (except HIV/AIDS) (15929) Intensive Care and Critical Care Medicine (1106) Medical Education (624) Medical Ethics (147) Nephrology (670) Neurology (6625) Nursing (346) Nutrition (999) Obstetrics and Gynecology (1148) Occupational and Environmental Health (957) Oncology (3344) Ophthalmology (979) Orthopedics (369) Otolaryngology (421) Pain Medicine (436) Palliative Medicine (130) Pathology (665) Pediatrics (1696) Pharmacology and Therapeutics (693) Primary Care Research (714) Psychiatry and Clinical Psychology (5461) Public and Global Health (9252) Radiology and Imaging (2207) Rehabilitation Medicine and Physical Therapy (1371) Respiratory Medicine (1197) Rheumatology (597) Sexual and Reproductive Health (715) Sports Medicine (530) Surgery (714) Toxicology (99) Transplantation (289) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'a02e88fbb9c752ad',t:'MTc3OTk4NDY4NQ=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();