Failure to follow up abnormal test results associated with cervical cancer in primary and ambulatory care: a systematic review

Abstract

Background

Cervical cancer is a preventable and treatable form of cancer yet continues to be the fourth most common cancer among women globally. Primary care is the first point of contact most patients have with health services and is where most cancer prevention and early detection occur. Inadequate follow-up of abnormal test results for cervical abnormalities in primary care can lead to suboptimal patient outcomes including higher mortality and decreased quality of life.

Aims

To explore the magnitude of and factors associated with, inadequate follow-up of test results for cervical abnormalities in primary and ambulatory care.

Methods

MEDLINE, Embase, Cochrane Library and CINAHL were searched for peer-reviewed literature from 2000–2022, excluding case-studies, grey literature, and systematic reviews. Studies were included if they reported on patients aged ≥ 18 years with no previous cancer diagnosis, in a primary care/ambulatory setting. Risk of bias was assessed using the Joanna Briggs Institute Critical appraisal checklists, appropriate to the study design. A segregated methodology was used to perform a narrative synthesis, maintaining the distinction between quantitative and qualitative research.

Results

We included 27 publications reporting on 26 studies in our review; all were conducted in high-income countries. They included 265,041 participants from a variety of ambulatory settings such as family medicine, primary care, women’s services, and colposcopy clinics. Rates of inadequate follow-up ranged from 4 to 75%. Studies reported 41 different factors associated with inadequate follow-up. Personal factors associated with inadequate follow-up included younger age, lower education, and socioeconomic status. Psychological factors were reported by only 3/26 studies and 2/3 found no significant association. System protective factors included the presence of a regular primary care provider and direct notification of abnormal test results.

Discussion

This review describes inadequate follow-up of abnormal cervical abnormalities in primary care. Prevalence varied and the evidence about causal factors is unclear. Most interventions evaluated were effective in decreasing inadequate follow-up. Examples of effective interventions were appointment reminders via telephone, direct notification of laboratory results, and HPV self-sampling. Even though rates of cervical cancer have decreased over the years, there is a lack of information on factors affecting follow-up in primary care and ambulatory settings, particularly in low and middle-income countries. This information is crucial if we are to achieve WHO’s interim targets by 2030, and hope to avert 62 million cervical cancer deaths by 2120.

Trial registration

PROSPERO ID CRD42021250136.

Introduction

Cervical cancer globally

Cervical cancer is the fourth most common cancer among women globally, with an estimated 604,100 new cases and 341,831 deaths in 2020 [1]. Even though preventable and treatable, cervical cancer continues to affect women and people with a cervix, is associated with substantial impacts on quality of life, and causes extreme suffering in late-stage disease. In 2020, the World Health Organisation (WHO) released a global strategy with a vision to eliminate cervical cancer as a public health problem [2]. The strategy proposes interim targets focusing on primary prevention (vaccination against HPV), secondary prevention (screening and treatment of pre-cancerous lesions), tertiary prevention (diagnosis and treatment of pre-cancer and invasive cervical cancer), and palliative care. Modelling has shown hundreds of thousands of lives would be saved if interim targets are met worldwide by 2030 and millions saved by 2120 [3].

Biology of cervical cancer and progression

The primary etiologic factor for over 95% of cervical cancers is persistent infection with high-risk Human Papilloma Virus (hrHPV) [4]. There are many strains of HPV, with types 16 and 18 accounting for approximately 70% of cervical cancer cases, and an additional 10–15 strains responsible for the rest [5]. Not all infections will lead to cervical lesions, but persistent HPV infection can lead to changes in the cervical cells, and these can develop into cervical cancer over decades, hence the importance of timely follow-up [5]. High-performance cervical screening tests can detect changes to cells as well as the presence and type of HPV infection prior to any cell changes. Results of cervical screening tests can be ‘normal’ (‘negative’): no HPV or cervical cell changes detected, or abnormal (‘positive’): HPV positive (presence of HPV infection) or abnormal cells (LSIL/HSIL/ASCUS—low/high grade squamous intraepithelial lesion or atypical squamous cells of undetermined significance). Results that are considered ‘abnormal’ or ‘positive’ require follow-up and/or treatment to avoid progression to invasive cervical cancer. Examples of follow-up can be via second-round testing, a colposcopy with/without a biopsy and, if necessary, excision treatment, [6] yet specific guidelines for follow-up will vary depending on the country and health care system.

Cervical cancer and primary care

Delays in the follow-up of pre-cancerous lesions in primary care, can lead to delays in cancer diagnosis, which, in turn, may result in suboptimal cancer outcomes such as higher mortality and decreased quality of life [7]. In many developed countries, primary care accounts for more than 80% of all health consultations in the general population and acts as gatekeeper for many interventions and specialist consultations [8, 9]. Defined by the WHO as the “best way to provide health care services to everyone, everywhere,” primary care is described as the most efficient way to achieve health for all [10]. Early detection, appropriate monitoring and treatment of positive or abnormal cervical screening results can lead to improved outcomes, and a reduction in adverse effects [11]. Importantly, adherence to cervical cancer guidelines can directly impact patient survival [12].

Adequate follow-up may be difficult to define, as there are multiple pathways. The WHO, in their “Guidelines For Screening and Treatment of Cervical Pre-cancer Lesions for Cervical Cancer Prevention” recommends two main approaches after a positive screening test: The “screen-and-treat approach”, where a decision is made to treat immediately after one positive test result; or the “screen, triage and treat approach”, where a second test may be required to decide treatment [6]. Further follow-up can be partial genotyping, colposcopy, visual inspection with acetic acid (VIA) or cytology [6].

There are different ways to define inadequate follow-up”; it may be due to a delay in performing a second test or treatment, or it may be defined as follow-up using an inappropriate screening test according to relevant guidelines (i.e., Pap smear instead of colposcopy). A range of factors leading to inadequate follow-up have been described. For example, a systematic review of studies published between 1985 and 1999 reported patient factors such as lack of social support, lack of understanding, and fear [13]. Health care system factors include inconvenient clinic hours, male providers, and insensitive staff. More recent systematic reviews reporting on adherence also mention social support, factors such as race and low socioeconomic status (SES) as well as provider/system factors [14,15,16,17]. However, current evidence from systematic reviews relies on data from earlier than 2010 and no reviews report exclusively on prevalence and factors associated with inadequate follow-up in primary and ambulatory care. Furthermore, primary care differs in each country’s local context, so it is crucial to understand the nuances of inadequate follow-up of abnormal cervical screening results in the ambulatory setting.

Aim and justification for current review

The WHO global strategy provides a comprehensive approach to cervical cancer prevention and treatment [2]. However, the interim targets fail to address inadequate or failure to follow-up of abnormal test results, which may lead to suboptimal outcomes and unnecessary harm. This review aims to address two key questions in relation to inadequate follow-up of abnormal test results associated with cervical screening in primary care: i) what is the magnitude of the problem in primary and ambulatory care and; ii) what are the precursors or predictors associated with inadequate follow-up.

Method

Study design

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were used to conduct a narrative, systematic review [18]. The review was registered on PROSPERO (registration ID: CRD42021250136). Covidence systematic review software was used for title and abstract screening, full text review and data extraction. A meta-analysis was not performed, due to the heterogeneity of included studies.

Search strategy

The search strategy (see appendix 1) was developed to include MeSH headings and word variations for the terms relating to ‘primary care, ‘follow-up’ and any screening and diagnostic tests relating to cervical cancer (e.g., Pap test, HPV, colposcopy). Searches were conducted across MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). Studies were included if they were published between 1 Jan 2000 and 17 March 2022. This timeline was selected as existing systematic reviews on related topics included studies from previous years, [13, 17] and we believed it relevant to assess follow-up behaviours over the last 20 years. Supplementary searching included a manual review of reference lists of included studies and citation tracking.

Inclusion and exclusion criteria

According to the PICO framework, studies were included if they referred to female adult populations (≥ 18 years) in primary/ambulatory care (P), who had undergone any screening and diagnostic testing related to cervical cancer and had received an abnormal/positive test result (I) and had not been followed up adequately according to local or national guidelines (O). As all types of studies were included, some studies did not have a comparator and outcomes varied according to study type. We included studies involving females < 18 years only if outcome data could be extracted for patients > 18 years old separately. Studies reporting follow-up of abnormal results that may lead to cervical cancer, including those reporting tests for screening, diagnosis of other gynecological cancers were included. We excluded case studies, unpublished work and articles not in English. Studies reporting only on children and adolescents (< 18 years); people with an existing cancer diagnosis; and follow-up conducted in tertiary care were excluded. Studies which solely reported appropriate or timely follow-up and not explicitly inadequate follow-up were also excluded. This decision was made to avoid assuming that women that did not have adequate follow-up corresponded to inadequate follow-up, as these concepts are not necessarily the same since these women may have accessed follow-up care elsewhere. Screening and full-text review was performed by two independent authors and conflicts were reached by consensus. Where consensus was not reached, opinion of a third independent author was sought.

Data collection

After studies were assessed against the inclusion and exclusion criteria, data were extracted from included studies, based on a standardized extraction template. Extracted data included study and participant characteristics; the number or percentage of women with abnormal test results that had inadequate follow-up; and barriers and facilitators to inadequate follow-up.

Statistical analysis

We used SPSS version 29.0.0.0 (241) to conduct a descriptive analysis of prevalence and study characteristics. The heterogeneity of study designs and outcomes precluded any form of meta-analysis.

Assessment of bias

The risk of bias of included studies were assessed using the Joanna Briggs Institute (JBI) Critical appraisal checklists, appropriate to the study design of the included studies [19]. Eight checklists were used, including the checklists for randomised controlled trials, quasi-experimental, cohort, cross-sectional, case–control, case series, qualitative and diagnostic accuracy studies. Studies that scored ≥ 80% were considered low risk of bias, between 60–80% a medium risk of bias, and < 60% were considered high risk [20]. Studies were not excluded based on their quality assessment scores [19].

Extraction and risk assessment were also performed by two independent authors and conflicts were reached by consensus. Where consensus was not reached, opinion of a third independent author was sought.

Definition of inadequate follow up of cervical cancer screening in primary care

To identify studies that related to inadequate follow up of an abnormal test result for cervical cancer, we adapted Zapka et al. “Steps and Interfaces from screening to diagnosis” (Fig. 1) which defines this period as the moment after receiving a positive/ abnormal test result (HPV positive (presence of HPV infection) or abnormal cells (LSIL/HSIL/ASCUS—low/high grade squamous intraepithelial lesion or atypical squamous cells of undetermined significance) to just before a cancer diagnosis [16]. This period is comprised of several steps, including referral for a diagnostic evaluation, appointment scheduling, and a follow-up test (Pap, HPV, colposcopy etc.). We selected all studies that reported results related to this period.

Fig. 1

Steps and interfaces from screening to cancer diagnosis. Modified from Zapka et al., [16]

Results

Overview

The combined search strategies identified 1524 titles, of which 1358 title and abstracts were screened, and 134 full text articles reviewed for eligibility (Fig. 2). Twenty-seven reports, including 26 studies, met the inclusion criteria.

Fig. 2

PRISMA flow diagram

Study characteristics

Characteristics of the included studies are described in Table 1. Twenty-seven publications were identified for inclusion in the review, including 26 primary studies [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46] and one secondary analysis of the original study data looking at cervical cancer prevention behaviours of the studied population [47]. The results of the secondary analysis are reported together with the primary study as most study characteristics were the same. Using the JBI risk of bias checklists, we assessed 12 studies as low risk of bias, [22,23,24, 30, 33, 34, 38, 40, 41, 43, 44, 46] 10 with a moderate risk [21, 25, 26, 28, 29, 32, 35, 37, 42, 45] and four studies with a high risk of bias [27, 31, 36, 39]. The detailed quality assessment can be found in Appendix 2.

Table 1 Characteristics of included studies

The included studies comprised seven RCTs [22, 23, 26, 29, 35, 39, 43] and seven cohort studies [21, 24, 31, 34, 37, 41, 44]. The remaining were cross-sectional [4], [27, 32, 36, 42] non-randomised experimental [2], [25, 40] case–control [2], [28, 45] qualitative [2], [30, 33] case series [1] [46] and diagnostic accuracy studies[1] [38]. Half of the studies were conducted in the USA [21, 22, 24, 26,27,28, 32, 33, 36, 37, 40,41,42, 46]. The remaining were conducted in Canada [3], [25, 36, 43] the UK [3], [30, 39, 45] Denmark [2], [34, 35] the Netherlands [2], [29, 38] New Zealand [1], [23] Hong Kong [1] [44] and Türkiye. [1] [31] The number of health care sites ranged from 1 to 2176, and the number of participants that had an abnormal test result requiring follow up ranged from 11 to 124,244. Even though the age of women included in the studies ranged from 14 to 86, for the purpose of this review, we only included data from women 18 years and older.

There were 7 population-based studies using data from large screening and testing datasets) [21, 29, 31, 34,35,36, 38]. The remining 19 were clinic-based. 7 studies included exclusively women from underserved populations (Latinas, low income, Maori and Criminal-legal involved) [22, 23, 26, 32, 33, 40, 42, 47] and 4 studies included only non-adherent women [23, 29, 33, 45].

While we grouped setting into four categories, due to the differences in health systems, we presented the setting from USA studies in more detail in Table 1. For non-USA studies, the setting was categorised into ambulatory/specialist clinics; primary care/general practice/family practice; hospital affiliated community clinic; and other/combination. Four studies were conducted exclusively in primary care/general practice/family practice [23, 34,35,36]. Three studies were conducted exclusively in ambulatory/specialist clinics [25, 39, 45]. The remaining studies were conducted in a combination of settings.

Definition of inadequate follow-up

Inadequate follow-up was defined as either no evidence of further action (follow-up tests and/or appointments) or an inadequate action according to guidelines or local protocol. A detailed definition of inadequate follow-up for each study is presented in Table 2. The majority (87.5%) of the included studies had a clear definition for inadequate follow up of an abnormal test result [21,22,23,24,25,26,27,28,29, 33,34,35,36,37,38,39,40,41,42,43,44,45, 47]. Of these, 70% defined it as a failure to attend the following appointment either with their clinician or for a follow up test [22,23,24,25, 27,28,29, 33, 37, 39, 40, 42,43,44,45] and the remaining 30% defined it as no evidence of further testing in the electronic medical record (EMR) [21, 26, 34,35,36, 38, 41].

Table 2 Definitions and rates of inadequate follow up

The source of the definition for inadequate follow up varied. Local or national guidelines informed the definition in 58.3% of studies [21,22,23,24, 26, 29, 33,34,35,36, 38, 41, 43, 47]. Seven of the included studies (30%) [25, 28, 37, 39, 42, 45, 47] used their own definition. Studies conducted in the USA used a variety of sources to establish their definitions, such as local guidelines, [26] or guidelines from different academic associations such as the National Cancer Institute, [21] the American Society of Colposcopy and Cervical Pathology [24] and the American Cancer Society [33]. Others formed their definition from a range of different evidence sources.

Time to follow-up after a positive/abnormal test result was specified in 13 studies and ranged from 2.5 months [24] to 2 years [21, 36] with a median of 6 months (IQR: 9). Source of data to identify adequate follow-up was either through EMR or chart review or national or local databanks.

Rates of inadequate follow-up.

Depending on the study design and country of origin, inadequate follow-up up ranged from 4% in a case control study from Canada, [25] to 75% in a cohort study from the USA, as shown in Table 2 [37].

Given the variety of the study types, the variability in the definitions of inadequate follow-up and the heterogeneity of results, we also chose to summarise prevalence according to study type in Table 3.

Table 3 Inadequate follow up by type of study^a

The lowest rates found were reported by Dunn et al. in a pre-post study measuring adherence of an on-site diagnostic colposcopy clinic [25]. The pre-intervention rates for inadequate follow-up were 13% which decreased to 4% post intervention (P < 0.001).

Prevalence for cohort studies ranged from 20.7% [44] to 75%. [37] Four studies [21, 31, 34, 44] were population-based and reported rates of inadequate follow-up from nationwide screening programmes, ranging from 28.3% [21] to 62% after a reminder message [34]. Chase, Lindau and Peterson [24, 37, 41] reported inadequate follow up for their clinic-based sample of women and their prevalence ranged from 38 to 75%. Prevalence for other types of studies is summarised in Table 3. We could not identify a specific trend throughout the years (increase or decrease of inadequate follow-up as technology improved).

Factors associated with inadequate follow-up

Factors associated with inadequate follow-up were examined in 16 of the included studies [21, 22, 24,25,26,27,28, 34,35,36,37, 40,41,42, 44, 45, 47]. A total of 41 factors associated with inadequate follow-up of abnormal cervical screening were classified into 4 domains; patient, clinical, provider and system (Table 4). For each factor, studies were grouped according to statistical significance of the association with inadequate follow-up (positive, negative, or non-significant).

Table 4 Factors associated with inadequate follow-up

Patient factors

Most of the factors explored were patient factors, with 15/16 studies exploring at least one factor in this domain. The most explored factors were age (n = 12), [21, 24,25,26,27, 34, 36, 40,41,42, 44, 45, 47] insurance status (n = 8) [24,25,26,27,28, 40, 42, 44, 47] and race (n = 7) [21, 26,27,28, 34, 41, 42, 47]. The association between age and inadequate follow-up was inconsistent, with mixed findings across the studies. Insurance status and race were slightly more consistent, with most studies reporting negative associations with (or decreased rates of) inadequate follow-up for having private insurance and being white (or country majority). A detailed description of these associations can be found in Table 4.

Psychological symptoms were explored in only three studies [22, 28, 42, 47]. Breitkopf et al. reported that high depressive symptoms were positively associated with inadequate follow-up, while high anxiety symptoms were associated with lower rates of inadequate follow-up [22]. Having a tertiary education was mostly associated with decreased rates of inadequate follow-up [22, 27, 28, 34, 37]. The associations of other frequent individual factors are summarised in Fig. 3.

Fig. 3

Most commonly assessed factors associated with inadequate follow-up

Clinical and provider factors

Clinical and provider factors were infrequently assessed. Factors such as type of visit or having a management plan showed inconsistent evidence of association [25, 26]. Dunn et al. found that women were significantly less adherent if they had been screened at an abortion clinic than if they had been referred directly after a Pap screening-specific appointment [25] while Engelstad et al. found the intervention to be equally successful if the reason for their initial Pap had been as a routine or a diagnostic appointment [26].

Severity of the lesion was measured in five different studies [25, 26, 40, 41, 45] and was not related to inadequate follow-up in all but one study [40].

System factors

These were measured in three, more recent studies [24, 35, 42, 47]. Internal referral to colposcopy (from the same clinic), [24] presence of a regular health care provider, [42, 47] and direct notification to women of cervical abnormalities results, [35] were all associated with lower rates of inadequate follow-up [24, 35, 42, 47].

Qualitative studies

We identified and analysed two qualitative studies [30, 33]. In exploring barriers and facilitators to follow-up, issues relating to communication were identified as a common theme in both studies. Goldsmith et al. explored women’s information needs for abnormal results and found the need for more didactic forms of information (diagrams) and the need to receive their results directly, with a knowledgeable intermediary other than the general practitioner (GP), outside primary care. Hunt et al. identified several barriers to follow-up including poor communication from the health care provider regarding their need to follow-up, mixed messages, getting follow-up care elsewhere, clinical errors, and inordinate follow-up requirements [33].

Intervention to increase adherence to follow-up after receiving an abnormal cervical cancer screening test result

Even though the aim of the review was not to identify effective interventions for adherence, but rather rates of inadequate follow up, we identified 7 RCTs testing interventions to decrease inadequate follow up. All RCTs but one [22] (6/7) were effective. Two studies reported on the use of self-sampling to increase adherence to screening, both with positive findings. Brewer et al., reported that sending women a self-sample kit for HPV testing at home resulted in statistically significantly (p ≤ 0.001) higher participation than an invitation to have a usual-care cytology sample in the clinic among Maori women (14.6% vs. 2.0%) [23] and Gok et al. described a 27.5% of compliance vs a 16.6% in the intervention vs control groups respectively with a difference of compliance of 10.9% (P < 0.001) after adjustment for those who were not eligible [29].

Other effective interventions described were: A counselling and outreach intervention for improving rates of follow-up of abnormal Pap smears [26]; a pre-clinic telephone contact intervention for prospective patients in a colposcopy clinic [39]; cytological surveillance in primary care compared with immediate referral for colposcopy examination in women with low grade abnormal results on cervical cytology tests [43]; and direct notification to women of cervical cytology results on follow-up rates [35].

Discussion

In this systematic review, we describe the prevalence of inadequate follow-up after receiving abnormal cervical screening results in the primary and ambulatory setting, and the factors affecting follow-up. We also summarise evidence found about interventions that have been shown to improve follow-up. Given the multiplicity of health systems around the world and the various definitions of what can be considered primary care, we opted for an inclusive approach and considered studies that were based in primary care as well as non-hospital based ambulatory care.

Definitions of inadequate follow-up

Definitions for inadequate follow-up varied. Most studies defined inadequate follow-up as either a) non-attendance to a follow-up appointment and/or b) the absence of further testing at various time points after abnormal test result. Most studies outside the USA, used national screening guidelines to construct their definitions of inadequate follow-up. All of these countries have national cervical screening programs [4]. While the USA has a national screening program in place, it is executed by many different providers, from family medicine clinics to women’s health clinics to specialist colposcopy clinics. This multiplicity of providers may be one of the reasons why researchers feel compelled to use a variety of sources to define inadequate guidelines suitable to their particular settings.

Prevalence of inadequate follow-up

Prevalence of inadequate follow-up varied substantially across the studies. In the studies conducted in the USA, the heterogeneity of definitions, different levels of risk of bias, along with the fact that follow-up in most studies were performed in a range of primary care/ambulatory settings, in very different populations, may account for the wide range of prevalence of inadequate follow-up encountered in the different studies.

Even though this wide range in the prevalence of inadequate follow-up of abnormal cervical cancer screening tests results is undoubtedly multifactorial, we hypothesise that differences in health systems and cancer screening programs may play an important role. According to the WHO, all locations mentioned in this review had a cancer screening program in place in 2021 [4]. Nevertheless, there are system differences that could explain the variation in rates. The USA, with the highest rates of inadequate follow-up, for example, does not have data available on whether programme/guidelines exist to strengthen early detection of first symptoms at primary health care level or whether a clearly defined referral system exists from primary care to secondary and tertiary care. All other locations report positively in these two aspects of their screening programs [4]. Likewise, all locations had programmes in place at the time of these studies [48,49,50,51,52]. However, for two of them, (Türkiye and Hong Kong) screening programs had newly begun. Türkiye started a cytology-based screening program in 2004, switching to HPV in 2014. [31] Hong Kong started theirs in 2004 [53]. The two studies conducted in the Netherlands reported inadequate follow-up for a colposcopy in 2020 was lower than in 2010. In 2017, the Netherlands replaced cytology testing for HPV. After their first HPV positive test, women are invited to perform a cytology test with their local GP [38]. This suggests that a comprehensive national screening program based in primary care and HPV testing is an effective way to increase adherence to follow-up after a positive result. Currently, of the countries in this study, only the Netherlands, United Kingdom and Türkiye have a program based on HPV screening. A systematic review on the impact of health systems’ influence on the speed of cancer diagnosis found that even though a causal correlation between healthcare system characteristics and cancer outcomes could not be found, factors such as centralisation of services, free movement of patients between primary care providers, access to secondary care, and the existence of patient list systems could impact cancer diagnosis delays and account for worse cancer outcomes in the countries studied [54]. Access to secondary care could be one of the reasons for the studies with low inadequate follow-up in this review. These were conducted in a women’s clinic in Canada. [25] and a colposcopy clinic in the UK [45]. They tested interventions to increase adherence by providing expedited access to colposcopy follow-up.

Factors associated with inadequate follow-up

We explored factors associated with inadequate follow-up of a positive cervical test result in primary care. Most factors had no statistically significant association with inadequate follow-up and findings were inconsistent across studies. For example, younger age was positively associated with inadequate follow-up in five studies, negatively associated in three studies, and found to be non-significant in four studies.

Race, low socioeconomic status (SES), and lack of health insurance have long been associated with lower cancer screening rates and poorer cancer outcomes in women. In the USA, Latina women have the highest incidence of cervical cancer whereas African Americans have the higher mortality rates followed by Latinas. [55] In 2019, the American Cancer Society reported higher cervical cancer screening rates for white women (77%) than for African Americans (75%), Hispanics (67%), Asian (66%), and American-Indian/Alaska-natives (70%) and for women with private insurance (80%) vs uninsured (54%).Overall screening rates decreased significantly from 2005 to 2019 even before Covid in all populations with higher numbers in minority populations (From 14 to 23% overall). Even though lack of access to health care services and insurance status continue to be reasons for underscreening, from 2005 to 2019, lack of access decreased significantly as the primary reason (from 21.8% to 9.7%). Instead, lack of knowledge (from 45.2% to 54.8%) and not receiving recommendations from health care professionals (from 5.9% to 12.0%) increased significantly, making the former the main cause for underscreening in the USA [56]. Sadly, this has not improved much in the last 30 years, when for example, a systematic review of studies published between 1985 and 1999 reported patient factors such as lack of social support, lack of understanding, and fear as main reasons for underscreening [13]. This is also the case in low- and middle-income countries where cancer prevention and outcomes are worse than in high-income countries due to multiple factors including lack of access to health services, low income, and low education among others [57]. In our review, race, particularly being white, was negatively associated with inadequate follow-up in three of seven studies that reported this variable; low SES and private insurance were only associated in a few studies. This may be due to some studies not using population-based data, instead focusing on specific minority populations (Latina, Maori etc.) therefore, it may have altered the possible association between race, SES and inadequate follow-up.

Psychological factors were seldom explored, and results were contradictory. Depressive symptoms were described as a risk factor for inadequate follow-up while anxiety symptoms were said to be associated with lower rates of inadequate follow-up [22]. This suggests that psychological symptoms or diagnosis of mental health issues may require further granularity when being explored as a factor for follow-up. Fish et al. [28] and Salyer et al. [42, 47] did not find a statistically significant difference, this could be due to a small sample size or lack of statistical power. The qualitative studies in our search described patients feeling “panicked” and “shocked” when receiving abnormal test results however, they do not describe how those reactions relate to follow-up. Rather, the studies discuss system factors and patient-provider communication as reasons for inadequate follow-up [30, 33]. Although communication was a key theme in both qualitative studies, communication is not mentioned as a factor for inadequate follow-up in any of the quantitative studies; personal factors were the point of focus instead. Physician factors and system factors were least likely to be explored, with only three studies including system-level factors and two studies including physician-level factors [24, 35, 37, 41, 42, 47].

Effective interventions to increase adherence of follow-up of abnormal cervical cancer screening

Although the primary aim of this study was not to identify effective interventions to increase follow-up of abnormal test results but rather describe factors that influence inadequate follow-up of abnormal cervical cancer screening in primary care, our search identified seven RCTs investigating different interventions to increase follow-up [22, 23, 26, 29, 35, 39, 43].

Positive results were seen by reducing barriers to access and by asking patients to self-sample or providing test results directly to the patients among others [23, 35]. These results are consistent with evidence that system-based interventions and interventions addressing patient and provider behaviours have proven effective in increasing adequate follow-up of abnormal cervical screening results in primary care [14].

One RCT evaluated cytological surveillance at 6 months performed in primary care compared with immediate referral for colposcopy at a hospital outpatient clinic for management of women with low grade cervical abnormalities [43]. Rates of inadequate follow-up were higher in the cytological surveillance arm compared to the ones referred for immediate colposcopy. A systematic review found evidence that women with abnormal tests preferred active follow-up, predominantly as immediate colposcopy, to observation and/or to repeated Pap smears. In this case, setting might be less important than the anxiety produced by the abnormal result and so women might be more willing to attend an immediate colposcopy appointment rather than observation in primary care [58].

Limitations

This review is limited by the lack of data from low- and middle-income countries. All of the studies identified in this search were conducted in high- or upper-middle income countries [59]. Inadequate follow-up is higher in middle- income/low-income countries and account for about 90% of new cases and deaths worldwide in 2020 [59, 60]. The existence of national screening programs facilitates the reporting of such statistics, yet we are unable to calculate the same prevalence for middle/low-income countries without organised cervical cancer screening programs. We had to exclude 14 studies for which there were no English full texts available. This may bias the information to represent only studies that can report their results in English (usually, again, high income countries).

There is also the risk of publication bias, as those studies with positive results might be more likely to be accepted for publication. During the initial screening for this review, we found most studies report on adherence to follow-up instead of inadequate follow-up, this limited the number and the quality of the information provided. We were unable to perform a meta-analysis given the heterogeneity of follow-up definitions and quality of included studies.

Deviation from protocol

One of our original aims was to investigate: “what are the adverse effects of inadequate follow-up?”. Once we started to investigate the literature more closely and developing the extraction tables, we decided that describing adverse effects of inadequate follow-up was outside of the scope of this review. There is strong evidence of the adverse effect inadequate follow-up poses to cancer outcomes [7, 11, 12]. Future reviews could investigate the psychosocial effects and the burden on quality of life caused by decreased compliance to cervical cancer screening.

Conclusion

Cervical cancer is the fourth leading cause of cancer death for women around the world. Primary care is defined as the first point of contact for health care and yet, there is incomplete and inconsistent evidence on the prevalence and factors that affect inadequate follow-up in primary care. We found that the prevalence and definitions of inadequate follow-up in primary care vary, and information regarding factors associated with it is contradictory. All information available comes from high- or upper-middle income countries with established screening programs with different levels of success. Further research is needed on factors that affect inadequate follow-up of positive cervical screening results in low- and middle-income countries without regular screening programs in place. Evidence of effective interventions to improve follow-up should be implemented more widely to improve outcomes for cervical cancer.