Self-Sampling Modality for Cervical Cancer Screening: Overview of the Diagnostic Approaches and Sampling Devices

Abstract

Cervical cancer remains the fourth most common malignancy among women worldwide. Despite well-developed prevention measures, incidence and mortality continue to rise, especially in low- and middle-income countries due to low screening coverage and unavailability of human papillomavirus (HPV) vaccination. The cervical cancer screening coverage could be improved by the implementation of a self-sampling modality for HPV testing. Multiple research pieces support the validity and reliability of a self-sampling modality as an alternative approach to clinician-collected samples for primary cervical cancer screening via HPV genotyping. Moreover, growing research evidence on the self-sampling modality reception shows high acceptance of the method among screened populations. Studies on the self-sampling approach economic efficiency also revealed a high cost-effectiveness of HPV testing through a self-sampling modality compared to other screening modalities for cervical cancer. It is specifically important for low-resource settings, which should use the self-sampling cost advantages to improve cervical cancer screening coverage by attracting underscreened populations. Overall, self-sampling modality has a higher participation rate and better patient satisfaction reported; thus, the method is highly recommended by the World Health Organization for cervical cancer screening.

1. Introduction

Cervical cancer is the fourth most common malignancy among women worldwide, with approximately 660,000 new cases reported in 2022 [1,2]. Despite being one of the preventable cancers through effective human papillomavirus (HPV) vaccination and screening programs, the incidences of cervical cancer continue to increase in many parts of the world. About 703,000 new cervical cancer cases are projected for diagnosis by the end of 2025, with about 373,000 deaths [3,4,5,6].

Persistence of the high-risk HPV types is associated and evidenced by Professor Harald zur Hausen to be the primary etiological factor of cervical cancer, accounting for more than 99% of cases worldwide [7]. Among over 200 HPV genotypes, HPV-16 and HPV-18 are responsible for approximately 70–75% of cervical cancer cases [8]. After initial infection of the basal epithelial cells, viral persistence of high-risk HPV types drives the initiation of carcinogenesis [9]. Integration of high-risk HPV DNA into the host genome leads to overexpression of the E6 and E7 viral oncoproteins, which inactivate the tumor suppressors p53 and retinoblastoma protein (pRb), respectively [9]. This results in cell genomic instability, deregulated cell-cycle progression, and accumulation of genetic and epigenetic alterations. Multiple risk factors, namely early sexual debut, smoking, multiparity, co-infection with other sexually transmitted infections, and compromised host immunity, increase the likelihood of long-term HPV infection persistence leading to initiation and progression of precancerous lesions to invasive carcinoma [7,8,9]. The pathogenesis of cervical cancer is a multiple-step sequence that typically takes years, making cervical cancer’s natural history very long. On the other hand, long-term development of this malignancy makes cervical cancer predictable and preventable through HPV vaccination and early screening/detection. Thus, cervical cancer is one of the avoidable cancers, and cervical cancer elimination could be achieved by proper application of effective prophylactic interventions [2,7]. However, despite the well-investigated etiology and developed prevention measures, cervical cancer remains a major public health challenge worldwide [2].

The World Health Organization (WHO) launched a global strategy for cervical cancer elimination called “Cervical Cancer Elimination Initiative” [10,11,12]. The program aims to decrease the cervical cancer incidence to ≤4 cases per 100,000 women-years and lower [12]. The strategy consists of three main points/requirements: (1) 90% of girls to be vaccinated against HPV by age 15 years; (2) 70% of women to be screened for cervical cancer with a high-performance test at least two times by age 45 years; (3) 90% of women identified with cervical precancerous lesions and/or cervical cancer to be treated according to the proper guidelines (“90-70-90” campaign) [7,10,12]. Investigations suggested that high-performance tests are HPV genotyping or co-testing (HPV + cytology). The “90–70–90” cervical cancer elimination campaign is to be achieved by 2030, which will ensure the elimination of cervical cancer by 2050.

Cervical cancer screening as a secondary prevention measure is one of the important steps for the timely diagnosis of precancerous cervical lesions and their early treatment to prevent invasive cervical cancer development [13,14]. Many cervical cancer screening methods have been developed since the 1950s, when Georgios Papanicolaou invented a cervical cytology test for the identification of atypical cervical epithelia [14,15,16]. Papanicolaou testing (Pap-test) was a “gold standard” test for decades until liquid-based cervical cytology and HPV genotyping were suggested to have a better specificity (SP) and sensitivity (SN) [17,18]. Research evidence shows that the SN of cytological screening with the Pap-test for the identification of high-grade precancerous lesions is no more than 64% [17,18]. Taking into account the concerns about false-negative results that might worsen the prognosis for patients with premalignant cervical lesions, HPV DNA testing was recommended by the WHO as a co-testing measure for cervical cancer screening [14,19,20]. The co-testing modality for cervical cancer screening features higher SP and SN than cervical cytology alone and was implemented into clinical practice by many high-income countries [20,21].

Many studies found that HPV DNA testing (PCR or HC2) for the detection of precancerous cervical lesions has an SN of up to 90% and an SP of >86%. A study from South Africa that assessed panels for cervical intraepithelial neoplasia (CIN) showed an SN of around 84% and SP of 87% [22]. Another study investigating HPV genotyping for high-grade cervical lesions found an SN of 86.7% for HPV genotyping, while the SN for cervical cytology was only 56% [23]. These findings suggest higher sensitivity of HPV genotype tests. Regarding co-testing, which implies HPV testing with cytology, a review from the International Agency for Research on Cancer (IARC) Handbook noted that co-testing had marginally higher sensitivity than HPV testing alone, but lower specificity [24].

Despite approaches to improving testing efficiency, the current cervical cancer screening coverage is considered insufficient to eliminate cervical cancer, and the target coverage of 70% set by the WHO has not been achieved, especially in developing countries with a high incidence of cervical cancer [13,14,25,26]. A review of screening programs in 15 European countries reported that the overall screening coverage was around 45%, with wide variation from 9.2% in Romania up to 86% in Sweden [24]. A report from Australia for 2014–2015 showed that the screening coverage among women aged 20–69 was about 56% [27]. The Organization for Economic Co-operation and Development (OECD) “Health for Everyone” report showed that cervical cancer screening coverage was about 71% among females of the target group in OECD countries [28]. The situation is even more dramatic in low- and middle-income countries (LMICs) [25,29,30]. In a cross-sectional study analyzing the situation with cervical cancer and screening from 55 LMICs, the self-reported coverage of cervical cancer screening was around 44% [31]. Another study from 16 LMICs covering data from 2010 to 2019 also revealed generally low screening coverage, with bottom rates reported among women in rural areas and those with less education or wealth [32]. A study by Bruni and co-authors (2022) analyzed data from 202 countries and estimated that in LMICs, screening coverage among women aged 30–49 years is no more than 11% [25]. Thus, improving cervical cancer screening coverage is essential for both the developed and developing worlds.

There are multiple factors affecting screening coverage, such as social and cultural disparities, lack of access to healthcare facilities and screening, unwillingness to undergo screening, hesitancy to visit healthcare professionals due to fear of expected results, unawareness of screening availability, etc. [13,14,31,32]. The currently implemented cervical cancer screening modalities (Pap-test, visual acetic acid inspection, HPV genotyping) require patients’ attendance at healthcare facilities for cervical sampling [14]. Thus, it is important to have an alternative cervical cancer screening modality that could improve screening coverage.

In recent years, the self-sampling approach, which does not require patients’ presence in the clinic, has become popular [14,33,34]. The self-sampling modality for cervical cancer screening requires the use of self-sampling devices, and the sample should be delivered to a laboratory for further testing. The self-sampling modality could become a good answer to the problem of low screening coverage as it offers a practical and efficient solution to the problem of low coverage of cervical cancer screening, particularly in LMICs. The traditional/conventional approach to screening, when the sample collection is performed by a clinician, usually faces many barriers, including a shortage of healthcare facilities, a lack of trained personnel, stigma, embarrassment, and cultural or logistical complications that prevent women from attending clinics [24,31,32,35,36,37,38,39]. Many studies have found that self-sampling overcomes most of these obstacles by enabling women to self-collect samples in a convenient setting and with minimal discomfort [35,36,37,38,39]. By encouraging females to take an active role in their health, the self-sampling modality could potentially expand screening achievements by promoting early detection of HPV infection and precancerous cervical lesions, thus supporting global efforts toward cervical cancer elimination.

This review aims to critically assess the existing evidence related to the utilization of self-sampling kits/devices for HPV testing as an up-to-date strategy for improving cervical cancer screening coverage. In addition, the review outlines the diagnostic performance of various self-sampling kits/devices, their acceptance by patients, and implementation challenges.

Objectives of the review are as follows:

(1)

To describe the diagnostic accuracy of HPV self-sampling kits/devices regarding their sensitivity and specificity;

(2)

Assess patients’ acceptance, preference for various devices, and experiences of women about self-sampling for HPV testing;

(3)

To identify barriers and facilitators that influence the implementation of the self-sampling modality for cervical cancer screening.

It is important to consider the role that HPV self-sampling can play in improving cervical cancer screening programs and contributing to the WHO “90–70–90” cervical cancer elimination strategy.

2. Materials and Methods

A non-systematic literature review was performed by searching the available publications on self-sampling modalities and various self-sampling devices utilized for cervical cancer screening. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). The narrative type of review was chosen for this study as it offers a general, qualitative synthesis of recent literature without limitations on the types of studies included. It is different from systematic reviews, which require only research papers to be included without flexibility in combining studies of different designs. Moreover, a narrative review allows for the detection of gaps in research, theoretical methodologies, and discussing future scientific directions.

The literature search was conducted in publicly available databases such as Scopus, PubMed, EBSCO, and Google Scholar. The data extraction spanned 10 years, with papers published from 2015 to 2025 being reviewed. The following inclusion criteria were applied: (1) papers published from 2015 to 2025; (2) discussing self-sampling modality for cervical cancer screening; (3) including the self-sampling method sensitivity and specificity, feasibility, and acceptability; and (4) published in English. Papers published before 2015 in languages other than English were excluded for review consistency and transparency. The following keywords and Medical Subject Headings (MeSh) were applied for the literature search: “uterine cervical neoplasm” (MeSH Unique ID: D002583), “cervical cancer”, “self-sampling”, “cervical self-sampling”, “urine self-sampling”, “self-sampling device”, “self-sampling device”, and “prevention” (MeSH Unique ID: Q000517). These keywords were used alone and in combination to cover all possible publications on the topic of the review. The most relevant publications to the subject of the discussion have been retrieved, read, evaluated by the authors, and utilized for the review.

3. Results and Discussion

The literature search, performed according to the set-up criteria, resulted in 122 papers eligible for inclusion in the review (Figure 1).

3.1. Self-Sampling Approaches for Cervical Cancer Screening

Multiple research pieces support the validity and reliability of the self-sampling modality as an alternative approach to clinician-collected samples for primary cervical cancer screening via HPV genotyping [14,21,31,33,35,36,37]. Self-sampling modality allows for reaching underscreened patients and helps to mitigate the effect of various factors on cervical cancer screening coverage. Moreover, an HPV self-sampling modality provides a favorable alternative of screening to the traditional clinician-taken test for religious populations with special requests for privacy [38].

Currently, the self-sampling modality for HPV testing has been found to be an effective and powerful strategy in all settings and conditions: low-, middle-, and high-income countries, all age groups, and any social and cultural clusters [14,21,31,34,35]. A meta-analysis by Arbyn et al. (2018) showed a similar SN for a self-sampling modality compared to conventional clinician-taken samples [39]. This study reported an SN of about 96% for cervical intraepithelial neoplasia (CIN) grade 2 and CIN grade 3+ for self-samples and an SP of 79% for <CIN grades 2 and 3 [39,40].

Currently, different self-collected samples were found to be valid for cervical cancer screening via HPV genotyping, but primarily vaginal and urine, as the cervical self-sampling procedure is difficult to perform [21,40,41].

3.1.1. Vaginal Self-Sampling

Testing for HPV for cervical cancer screening through self-collected vaginal samples could serve as a potentially effective option to increase screening coverage [42,43]. Research evidence has revealed that HPV testing performed by using self-collected vaginal samples demonstrated similar accuracy compared to clinician-collected cervical samples [39,43,44].

The vaginal self-sampling process can be carried out by women themselves at home or in a private or public healthcare facility [41,42]. For vaginal self-sampling, a woman should receive a testing device/kit from a healthcare professional or via mail. It could be a single-use cervical brush, swab, or card to collect a cervicovaginal sample supplied with instructions. The process requires carefully inserting the brush/swab into the vagina, followed by delicate rotation of it to obtain an adequate sample (Figure 2) [41]. After removing it, the swab should be placed either into a special envelope or into the transport medium tube and sent to the laboratory for further analysis.

Researchers report the SN of self-collected vaginal samples to be 85% [38] to 93% [44,45] agreement between the clinician-collected and self-collected vaginal samples of 88% [42]. Moreover, the vaginal self-samples and the clinician-collected samples revealed the same SN of 92.8% and SP for the detection of high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS) [45]. The researchers also reported that self-collected vaginal HPV genotyping is more sensitive compared to urine self-samples for HPV DNA detection [46].

3.1.2. Urine Self-Sampling

Some studies described the use of urine sampling for HPV genotyping as part of cervical cancer screening [39,44,45,47,48,49]. As vaginal self-sample collection has an invasive component, urine self-sampling for HPV testing, which is non-invasive, may be more acceptable to some patients or cultures [40]. Moreover, it is a good alternative for cases when non-invasive testing is preferable [48]. Urine sampling is also used for monitoring HPV prevalence among women to determine the effect of HPV vaccination [45,46].

For urine self-sampling for HPV genotyping purposes, a first-void urine sample is required using a special urine collection kit that is usually prefilled with urine conservation medium [40,41]. Collection of a 20 mL sample, including the conservation medium, is found to be sufficient for HPV genotyping as part of cervical cancer screening [40,41]. Similar to the vaginal self-sampling approach, urine self-sampling could be performed at home or in a clinic (private room) [41].

Several studies have investigated the sensitivity and specificity of vaginal and urine self-samples for HPV detection [45,46]. A study by Asciutto and co-authors (2017) identified a high SN of the vaginal self-samples (more than 96%) and urine self-samples (84%) for the detection of HPV when compared with clinician-collected cervical samples [45]. Another study showed that the SN for HPV DNA detection as a part of cervical cancer screening via urine self-samples was 58% (ranging from 47% to 68%), and the SP was 85% (ranging from 66% to 94%) compared to vaginal self-samples [44,45,46]. The studies concluded that vaginal self-collected samples are more sensitive for HPV testing compared to urine self-collected samples [45,46]. Researchers also reported an SN of 76.3% for HSIL and AIS detection through urine samples [45].

3.2. Self-Sampling Devices/Kits Used for Cervical Cancer Screening

A wide range of convenient devices produced by different companies is available on the market (

Table 1. Self-sampling devices overview.

Self-Sampling Device	Self-Sampling Approach	Producer	Validated HPV Testing Platforms	Studies Testing the Devices
Aptima Multitest Swab Specimen Collection Kit	Vaginal	Hologic Inc., Marlborough, MA, USA	Hologic Aptima	[51,52]
BGI Sentis HPV card	Vaginal	BGI Genomics, Shenzhen, China	Sentis™ HPV Genotyping Test	[53,54]
Catch-All Swab	Vaginal	Epicentre, Madison, WI, USA		[55]
Cervex-Brush®® Combi	Vaginal	Rovers Medical Devices, B. V, Oss, The Netherlands	Roche Cobas 4800, BD Onclarity, Hologic Aptima	[56,57,58,66]
Cepillo Endocervical/Cervical Brush/Cyto-Brush + DNA sample storage card	Vaginal	Ningbo HLS Medical Products Co. Ltd., Ningbo, China BGI Biotechnology (Wuhan) Co. Ltd., Wuhan, China	BD Onclarity	[54]
Colli-Pee™	Urine	Novosanis, Wijnegem, Belgium	Roche Cobas 4800, Abbott Alinity m HR HPV, BD Onclarity, Hologic Aptima	[40,56,57,75]
Copan ESwab®®	Vaginal	Copan Italia, Brescia, Italy	ABI GeneAmp®® 9700 PCR System	[60]
Cytobrush Plus	Vaginal	Medscand, Malmo, Sweden	Roche Cobas 4800, BD On-clarity, Hologic Aptima	[61]
Dacron swab	Vaginal	Invista North America S.a.r.l., Wichita, KS, USA	Hybrid Capture®® 2 High-Risk HPV DNA Test (HC2; Qiagen)	[62,63]
Deplphi Screener	Vaginal	Rovers Medical Devices B.V., Oss, The Netherlands	Roche Cobas 4800, Abbott Alinity m HR HPV, Hologic Aptima	[39,58,64,75]
Digene cervical brush	Vaginal	Digene Corporation, Gaithersburg, MD, USA	HPV DNA Tests by Cervista	[65]
Evalyn brush	Vaginal	Rovers Medical Devices B.V., Oss, The Netherlands	Roche Cobas 4800, Abbott Alinity m HR HPV, BD Onclarity, Hologic Aptima	[39,58,64,65,66,67,75]
FLOQSwab	Vaginal	COPAN Diagnostics Inc., Brescia, Italy	Roche Cobas 4800, Abbott Alinity m HR HPV, Hologic Aptima	[40,67,68]
Elute Micro Card (FTA card)	Vaginal	GE HealthCare, Hatfield, UK	Roche Cobas 4800, Abbott Alinity m HR HPV	[69,70]
Genelock	Urine	ASSAY ASSURE, Sierra Molecular, Princeton, NJ, USA	Roche Cobas 4800	[71]
HerSwab	Vaginal	Eve Medical, Inc., Toronto, Canada	Roche Cobas 4800, Abbott Alinity m HR HPV	[40,55,72]
Home Smear Set Plus®®	Vaginal	Asica Medical Industry Co., Ltd. (global network), Tokyo, Japan	Roche Cobas 4800	[73]
“Just for Me”	Vaginal	Preventive Oncology International Inc., Cleveland Heights, OH, USA	Not reported	[74]
Mía by Xytotest®®	Vaginal	Mel-Mont Medical, LLC, Mexico City, Mexico	BD Onclarity, Hologic Aptima	[57,66]
Multi-Collect swab	Vaginal	Abbott GmbH & Co. KG, Wiesbaden, Germany	Abbott Alinity m HR HPV	[75]
SelfCerv Self-Collection Cervical Health Screening Kit	Vaginal	Ilex Medical Ltd., Johannesburg, South Africa	Roche Cobas 4800, Hologic Aptima	[76]
SelfCervix®®	Vaginal	Not reported	Hologic Aptima	[77]
Qvintip	Vaginal	Aprovix AB, Uppsala, Sweden	Roche Cobas 4800, Hologic Aptima, BD Onclarity	[40,72,75,78]
Urine Sampler	Urine	Any available	Roche Cobas 4800, Abbott Alinity m HR HPV, Hologic Aptima, BD Onclarity	[45,65,71]
Viba brush	Vaginal	Rovers Medical Devices B.V., Oss, The Netherlands	Hologic Aptima	[57]
XytoTest medical device	Vaginal	Mel-Mont Medical, Doral, FL, USA	Abbott RealTime HR HPV test	[78]

). All of them are well-validated in different studies, and their reliability and acceptability are analyzed in a recent systematic review [14,40,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78]. The majority of available devices are designed for vaginal self-sampling (Table 1). However, it is important to note that any of the tools designed for vaginal self-sampling could be used for cervical sampling by a clinician, improving the screening procedures. Moreover, vaginal self-sampling kits are applicable for utilization among the transgender population to implement anal self-sampling for HPV testing [50]. This brands the available devices universal and makes cervical cancer screening procedures easier, more efficient, and effective. A choice of a device for self-sampling could be made by a local healthcare provider based on specific factors such as laboratory infrastructure, screening logistics, target population, climate features, and cultural perspectives [31,42].

There are two types of shipping options: self-specimens could be dissolved in a special transporting medium or sent as a dry sample [42]. Dry devices appear to be more convenient for shipping, as there is no risk of spillage or leakage of the specimen [42]. However, samples shipped in transport media have the advantage of better stability of the specimen, ensuring further reliability of the test.

The most popular self-sampling devices for vaginal use are the Evalyn Brush, Cervex-Brush, FLOQ Swab, Delphi Screener, and Qvintip (Table 1) [14,42]. Many studies have demonstrated that these kits have been found to be reliable in terms of HPV detection compared to conventional clinician-taken samples [14,41,42,64,72,79].

Among the kits designed for urine specimens’ self-collection for HPV genotyping, Colli-Pee™ is the most popular, and its reliability is validated in multiple studies [14,41,59,75].

3.3. Laboratory Tests for HPV Identification from Self-Collected Samples

Various methods are utilized for HPV testing. These methods could be divided into two groups: HPV DNA and HPV RNA assessment (Table 1) [80,81]. The most commonly used are polymerase chain reaction (PCR) with HPV DNA identification [39,80,81]. However, some studies utilize HPV RNA testing as a primary method [36].

In studies investigating PCR accuracy for self-samples to detect HPV DNA, it was found that PCR demonstrates similar accuracy for both self-collected and clinician-collected samples: the SP “to exclude CIN2+ was 2% or 4% lower on self-samples than on clinician samples” [39]. Another systematic review on the efficiency of HPV RNA testing revealed that high-risk HPV testing with an mRNA-based assay had a similar SN for CIN grades 2 and 3 and a slightly higher SP than DNA tests [36].

Currently, the research evidence supports PCR-based tests for use in self-sampling protocols [80], and the majority of cervical screening programs based on a self-sampling modality utilize PCR genotyping for the identification of high-risk HPV types.

3.4. Patients’ Acceptance of Self-Sampling Modality

Although research evidence shows a high reliability of self-sampling modality for cervical cancer screening via HPV genotyping, patients’ acceptance of the method is an important determinant in the implementation of the approach. There are many factors with a potential impact on acceptance of the self-sampling approach (Figure 3).

Many studies investigated the acceptance of the self-sampling approach among various populations [71,78,82,83,84]. According to recent reviews evaluating self-sampling device acceptance, the self-sampling modality had an overall good acceptance among the studied populations [14,85]. The vast majority of analyzed studies found the self-sampling procedure to be highly acceptable, “with a good potential to improve cervical cancer screening” coverage [14,71,78,84]. These studies reported high acceptance of the Evalyn Brush kit, FLOQ Swab, Delphi Screener, and Colli-Pee, which ranged from 84.2% to 100% [14]. The self-sampling modality was found to be appropriate for large-scale cervical cancer preventative interventions. The vast majority of the self-sampling modality users did not report any unpleasant or inconvenient experiences while performing self-sampling, such as pain, discomfort, or embarrassment [85]. Only a few studies reported poor acceptance due to some factors, such as a low level of education and insufficient familiarity with the method [82,83]. Limited knowledge about self-sampling leads to doubts about the credibility of the screening results and remains a barrier to the wider acceptance and introduction of a self-sampling modality for cervical cancer screening [86]. Thus, to increase the acceptance of this potentially effective approach, educational interventions about self-sampling modality techniques and logistics should support the wide implementation of self-sampling to increase screening coverage among women, especially in resource-limited countries [14,85,86].

Importantly, a good acceptance of self-sampling screening was reported among special populations like transgender individuals assigned as female at birth and HIV-positive patients [48,50,86,87]. It is also well-accepted by religious women and other populations with low adherence to screening due to spiritual and cultural beliefs [38,88].

3.5. Comparison of the Self-Sampling Approach Efficacy in Urban and Rural Areas

Considering socio-demographic differences between urban and rural populations, there might be a discrepancy in the success of utilization of the self-sampling approach. Many investigators analyzed this anticipated issue [89,90,91,92,93]. In these studies, offering self-sampling for HPV identification as a part of cervical cancer screening practice has been reported to consistently increase uptake compared with standard invitation or clinician-collected sampling. Furthermore, the outcome is usually much better among under-screened women and groups that live in remote areas/rural settings [89,90].

Studies also show the overall high acceptability among women living in rural areas [91,93]. The major advantage of self-sampling for cervical cancer screening for rural women is accessibility and convenience, as they do not need to travel to a clinic, since many rural areas do not have appropriate clinical settings. The advantages of the self-sampling modality drive stronger preferences for self-sampling in rural contexts than in urban contexts. Acceptability among urban participants is also high, but logistical barriers, such as those related to access to the clinic, generally tend to be less pronounced. Cultural and literacy factors influence the preferred delivery modes and instructions [91,94].

Self-sampling programs in rural areas are even more effective if combined with active community strategies, for example, distribution by community health workers or mail-out/return systems [92]. It is especially effective if accompanied by clear, locally/culturally adapted instructions and supported follow-up communications. Clinical trials pairing self-sampling with outreach in the community had better results in terms of screening and linkage to diagnosis and treatment compared to passive strategies. However, while organizing self-sampling in rural settings, it is important to keep in mind that reliability of sample transport, laboratory capacity, and referral for follow-up are also essential elements. These steps are usually more problematic to implement in rural settings [92].

From a practical standpoint, to ensure high acceptance and efficacy of the self-sampling modality for cervical cancer screening in rural areas, a community-integrated delivery approach is prioritized through the distribution of self-sampling kits during home visits or community events. Moreover, clear pictorial instructions could improve the reliability of the approach. It is also essential to organize a sample return and follow-up pathway. All these steps are vital to increase uptake and ensure linkage to care [92,95,96]. In urban settings, mail-out kits, pickup points in clinics, or distribution via pharmacies could work well to improve the coverage; however, this requires attention to specific underserved urban subgroups (migrant populations or people living in slums) [97].

3.6. Barriers and Facilitators for Self-Sampling

Despite high acceptability, the use of self-sampling in practice could be influenced by a range of facilitators and barriers. Barriers to cervical cancer screening may be viewed as procedural, informational, logistical, or structural (

Table 2. Barriers and facilitators for the self-sampling approach.

Area of Interest	Barriers	Facilitators
Logistical	No regular provider or nearby clinic; inconvenient hours; work/child/elder care demands; transport/parking/childcare costs; preference to avoid male clinician; hard-to-navigate services	Home or in-clinic self-sampling; flexible timing; prepaid mail-back kits; option to choose method
Procedural	Anticipated pain/discomfort; embarrassment; dislike of speculum/Pap; privacy concerns in small communities	Greater privacy and autonomy with self-collection; fewer intimate procedures
Knowledge-related	Fear of doing it “wrong” or self-injury; doubts about HPV test accuracy; low perceived risk; fear of positive result; limited info after abnormal results	Clear step-by-step instructions; helplines/video guides; provider recommendation; option for female provider
Cultural and Social	Stigma/taboos around bodies/sexuality; recent immigration; distrust from historical harms; services not culturally safe	Co-designed, culturally sensitive materials; community-driven delivery; affirming caregiving/traditional roles; sustained trust-building

). Logistically, women refuse screening because of limited access to health facilities, inconvenient clinic hours, childcare, a job, or elder care obligations [98,99,100]. Additional costs are also involved for women, including loss of income while taking time off from work or even paying for transportation to get there [101].

Another barrier arises from the gender of the healthcare provider. While some women express discomfort when seeing male physicians, others feel dissatisfied because they are not offered culturally competent care [99,101]. Even though this is for self-collection of samples, healthcare professionals’ gender could appear as a barrier because women still have to interact with the provider to obtain a kit or its instructions, return a sample, or discuss the results. Sometimes, due to cultural specifics, it could be embarrassing to discuss all these items with a male provider. Thus, a woman may decide to avoid a visit due to discomfort with a male specialist, or she may not even reach the stage of choosing self-collection.

Procedural obstacles also reduce care-seeking. While many women consider Pap-tests invasive, uncomfortable, or embarrassing, there exist legitimate concerns of privacy loss [98,101,102]. Due to the lack of confidentiality in community clinics, women from small or tightly knit communities might avoid visiting [100].

Personal information and knowledge are also important to consider. Some women are worried about how to self-sample because they might hurt themselves or do an improper collection of the sample [99,103]. Others become suspicious about the results of the HPV test or simply do not understand the link between HPV and cervical cancer [98,104]. Since many believe themselves to be at low risk, there is not much motivation to go for a screening. A few others stay away from screening due to the fear of testing positive and having insufficient information to explain the result [101]. Compounded with these enormous factors is a cultural stigma surrounding women’s bodies and sexuality, and the mess faced by immigrants and indigenous people at the opposite end [102,105].

Despite the existing barriers, there are multiple facilitators that could potentially improve the use of self-sampling in the face of such challenges (Table 2). One of the main advantages of this method is that it is convenient and flexible. Women can perform sample collection either at home or while attending regular clinic appointments [100,101]. The launching of prepaid kits through the mail decreases shipping costs and aids in faster returns [106]. In addition, self-collection provides women with greater autonomy and privacy since they are able to decide on the provider-collection or self-collection option according to their comfort preference [104].

Another barrier to the self-sampling modality is the lack of providers’ support for primary HPV testing. A large majority of clinicians are resistant to implementing the most recent management guidelines that promote primary HPV testing over Pap-test [17,26,107]. Thus, health professionals’ support is still one of the most significant factors. Females’ willingness to attend is greatly increased by access to female healthcare professionals and peer-to-peer recommendations from experienced medical practitioners [100,106,108]. Medical professional support enhances long-term trust in the screening process, not just on the first occasion [101].

Lastly, culturally responsive procedures and educational materials that are developed by communities that comprehend women’s traditions and roles strengthen screening responsibility and responsiveness [102,106,109]. While self-sampling uses most procedural and structural precautions, additional innovations like patient education, physician acceptance, and appropriate culturally sensitive screening delivery are necessary for it to be effective.

3.7. Cost-Effectiveness of Self-Sampling Modality for Cervical Cancer Screening

Several assays/testing systems are approved for primary high-risk HPV testing with self-collected samples (Table 1), including those from Roche (Cobas 4800 HPV Test), Hologic (Aptima HPV Assay), BD (Onclarity HPV Assay), and Abbott (Alinity m HR HPV Assay). Each of these testing platforms provides high clinical validity and accuracy for the detection of HPV in clinician-collected and self-collected samples [39,40,59,66,67]. Besides this, economic evaluations reflect that these automated, high-throughput platforms have proven to be cost-effective when implemented for large-scale screening initiatives, especially in combination with a self-sampling modality for cervical cancer screening that increases coverage and reduces personnel costs [39,60,110,111,112].

The possible economic benefits of the self-sampling modality for cervical cancer screening are one of the important factors for the wide implementation of the approach, especially for low-resource settings. Many studies investigated the cost-effectiveness of self-sampling for HPV testing [85,110,111,112].

A systematic review on the cost-effectiveness of available cervical cancer screening methods in developing countries reported a high cost-effectiveness of HPV testing through a self-sampling modality compared to other screening modalities for cervical cancer [110].

Another study of self-sampling economic benefits assessed the cost-effectiveness of different self-sampling kits [113]. The study showed that the self-sampling modality for cervical cancer screening is cost-effective; however, the researchers recommended taking into account all confounding factors, such as the device type, materials used, etc.

The study by Boyard et al. (2022) revealed that “home-mailed delivery of a vaginal self-sampling kit is a cost-effective” alternative that improves cervical cancer screening coverage [112]. Another study reported that even repeated self-sampling for HPV testing requires a lower cost for cervical cancer screening than healthcare professional-collected smears [114]. Moreover, this approach increased participation in the screening and improved the detection of CIN grade 2 [114].

In a recent Chinese study, the self-sampling modality for HPV testing on an annual basis was found to be cost-effective among a special population, men who have sex with men [115]. It was reported that self-sampling has the potential to significantly reduce the domestic cost of HPV testing and yield favorable economic outcomes for future self-sampling initiatives.

In

Table 3. Comparison of self-sampling device costs.

Self-Sampling Kit	Cost per Kit (USD)	Comments/Cost-Effectiveness
Evalyn Brush	~$5–7	Validated in multiple trials in European countries and now extensively used; cost-effective for mass screening
Copan FLOQSwab/ESwab	~$4–6	Validated in many studies; cost-effective for LMICs; easy to store and transport
Delphi Screener	~$7–9	Preferable for high accuracy; has a slightly higher cost
Qvintip	~$6–8	Validated in large population programs; has good acceptance; lower material cost
HerSwab	~$8–10	High user satisfaction; however, slightly more expensive
Colli-Pee™	~$9–11	Higher price due to integrated preservation system; however, shows cost-effectiveness due to high acceptance and high participation rate
BGI Sentis Card/FTA Card	~$3–5	Card; low cost of the card; suitable for remote or low-resource regions
SelfCerv	~$4–6	Designed for LMICs; cost-effective
Mía by XytoTest®	~$5–7	Validated in Latin America; low cost and high acceptability

, a comparative summary of various self-sampling devices is presented, based on available resources.

The overview of costs for self-sampling kits shows that generally, self-sampling devices are cost-effective compared to clinician-collected approaches, especially when used in community- or mail-based screening models. Dry-sampling kits, such as BGI Sentis and FTA Card, are relatively inexpensive, while Colli-Pee™ and Delphi Screener appear to be more technically advanced formats, which increases their prices. Studies conclude that home-mailed or self-administered sampling programs are associated with reduced overall screening costs and increased participation, especially in low-resource settings [112,113,114].

Thus, offering women a self-sampling device and organizing cervical cancer screening via the self-sampling modality could potentially improve screening uptake at a lower price, confirming its cost-effectiveness [81]. Considering that the self-sampling modality requires similar laboratory performance as clinician-collected sampling but without the costs associated with a healthcare professional’s involvement, the economic benefits of self-sampling are obvious. Moreover, the self-sampling modality has a higher participation rate and better patient satisfaction reported [14,116].

3.8. Self-Sampling Modality Strengths and Limitations

The WHO recommends HPV self-sampling as an additional modality for cervical cancer screening for women aged 30–60 years old [117]. Moreover, the American Society for Colposcopy and Cervical Pathology (ASCCP) released specific recommendations for self-collected samples for HPV testing for primary screening [118]. It reports the acknowledgement of evidence that self-collected vaginal specimens have clinical equivalence to clinician-collected samples. The revised management algorithm permits self-collected HPV testing as an option among underscreened women or those who prefer home testing. In this view, self-sampling modality for cervical cancer screening could play a significant role in the identification of HPV high-risk types [119]. According to the WHO estimations, a self-sampling modality could potentially be helpful in reaching a global target of 70% for cervical cancer screening coverage by 2030 [120].

Advantages of self-sampling include the following main points:

(1)

Self-sampling allows the sample collection to be completed in a short period without heavy input from medical workers, making positive patient management more centralized and efficient, lowering the screening cost significantly;

(2)

Through the binding set between the treatment and recheck of positive patients, a closed-loop process is established for cervical cancer prevention, ensuring standard diagnostics and treatment for positive patients and meanwhile, maximizing their treatment rate;

(3)

Local staff receive training in the management process of positive patients, allowing them to undertake positive patient management and long-term follow-up; meanwhile, by focusing on positive patients’ management, they can improve their skills in diagnostics and treatment in a short period;

(4)

Cervical cancer screening is carried out at the basic level, improving the capability of basic medical units in cervical cancer prevention and constructing a sustainable cervical cancer prevention system.

If widely utilized, this approach may result in the implementation of a “more women-friendly screening program” with higher coverage and mitigate the factors affecting screening attendance [119]. Moreover, self-sampling for HPV testing could strengthen community-based approaches to support socially and culturally acceptable screening programs [120]. Overall, the self-sampling modality has the potential to improve the feasibility and sustainability of cervical cancer screening.

However, together with the potential benefits of self-sampling, some important limitations should be noted here. The implementation of self-sampling requires multiple-step efforts, including but not limited to the healthcare providers’ training, educational interventions, development of a special guideline or management algorithm for cervical cancer screening via the self-sampling modality, and availability of an appropriate platform for testing.

Although self-collection for primary HPV testing has been recommended in the most updated ACCSP guideline [118] and was approved in the United States and many other countries worldwide, the availability of validated testing platforms remains limited. Currently, only the Cobas 4800 (Roche) and BD Onclarity assays are FDA-approved for HPV testing on self-collected samples, which restricts the large-scale implementation of a self-sampling modality as an effective cervical cancer screening approach [121]. In contrast, the United Kingdom and several European countries have successfully integrated self-sampling into national cervical screening programs, using validated assays such as Aptima (Hologic), Alinity m (Abbott), and BD Onclarity for primary cervical cancer screening based on HPV detection [58,66,67,75]. Large-scale studies from Europe, such as the VALHUDES and Dutch population screening programs, have demonstrated comparable diagnostic accuracy, improved participation, and cost-effectiveness with self-sampling compared to clinician-collected specimens [39,58,75]. This disparity underscores a global implementation gap, where governing limitations and slower clinical adoption delay wider utilization of self-sampling modalities despite vigorous evidence from European practice [39,40,58].

Healthcare providers’ acceptance of self-sampling modalities should also be discussed. There have been multiple studies performed to investigate patients’ acceptance of the self-sampling modality, including the various factors involved: socio-demographic, cultural, religious, etc. However, a very limited number of studies discussed the acceptance of this alternative screening modality among healthcare providers. Despite the statements of the updated guideline [118], many specialists mostly rely on clinician-collected specimens. Studies from the United States highlight that a substantial proportion of clinicians continue to perform Pap-tests and hardly recommend HPV self-sampling as an alternative sampling modality [107,122]. Thus, training should be organized for healthcare professionals aiming to educate them on how to explain the self-sampling procedure to a potential screening participant [31,80].

Moreover, before the implementation of self-sampling, cultural context should be taken into consideration. This means that before nationwide implementation of self-sampling for cervical cancer screening, a validation study should be performed among the population/ethnic group to understand whether the method is feasible and acceptable for this particular population [14]. Without proper validation of the method and particular self-sampling kits in a specific cultural setting, the self-sampling modality might face difficulties in the implementation stage, such as barriers related to low acceptance, low confidence, and patients’ preference for clinician-collected specimens [14,85]. Another challenge is the economic component, such as purchasing self-sampling kits, which will require some budget. Moreover, transportation of the self-collected samples to a laboratory might present its own issues. There could also be some laboratory-based technical differences in sample analysis compared to clinician-collected specimens. Stakeholders should weigh the advantages and cost-effectiveness of the self-sampling modality for cervical cancer screening to make an appropriate decision on the implementation of the method as a part of nationwide screening.

4. Conclusions

The self-sampling modality is a promising opportunity to improve cervical cancer screening coverage. The WHO recommends implementing self-sampling for cervical cancer screening, aiming to achieve a target level of screening coverage of 70%. Currently, research evidence reveals good acceptance of the cervical self-sampling modality, with high reliability of the HPV test performed on self-samples. Healthcare providers should consider the self-sampling modality as an option for cervical cancer prevention and develop relevant screening protocols. It is especially important as self-sampling allows for attracting the underscreened population, which avoids screening due to multiple factors, including hesitancy toward gynecologic examinations.