Abstract
Background/purpose
South Asia has a high burden of oral cancer (OC); however, delays in diagnosis remain under-researched. The study investigated delay intervals in OC diagnosis and the contributing factors in rural Pakistan, considering its unique sociocultural context.
Materials and methods
This multi-center cross-sectional study employed a structured questionnaire to interview 152 oral squamous cell carcinoma (OSCC) patients. The diagnostic intervals were determined using the Aarhus Statement. Logistic regression assessed the association between independent factors and delay types.
Results
Patient delays occurred in 76.3 % of cases, mostly due to appraisal delays (65 %), while diagnostic delays appeared in 51.3 %. Median durations for patient, diagnostic, and total delays were 3, 1, and over 4 months, respectively. Appraisal delay was associated with infrequent dental visits (adjusted odds ratio [AOR]: 11.04, confidence interval [CI]: 2.29–81.53), advanced stage OSCC (AOR: 5.42, CI: 2.35–13.03), and rural residence (AOR: 3.99, CI: 1.75–9.35). Help-seeking delay was linked to use of home remedies (AOR: 5.74, CI: 2.35–14.46) and homeopathy (AOR: 4.72, CI: 1.90–11.91). Patient delay associated with advanced stage OSCC (AOR: 7.73, CI: 3.28–19.12) and rural residence (AOR: 3.91, CI: 1.62–9.69). Diagnostic delay was influenced by patients’ lack of OC knowledge (AOR: 7.33, CI: 1.30–51.74), more than two visits before biopsy (AOR: 52.88, CI: 1.50–270.88), and initial treatment with analgesics (AOR: 13.37, CI: 3.68–60.99) or antimicrobials (AOR: 3.95, CI: 1.06–18.23).
Conclusion
Delays in OC diagnosis arise from inadequate patient awareness, rural residence, traditional and complementary medicine use, and health system challenges. Improving healthcare access and public awareness are crucial.
Keywords: Delayed diagnosis, Health services accessibility, Oral cancer, Pakistan, Rural health
Introduction
Oral cancer (OC) is a significant global health challenge, with 389,846 new cases and 188,438 deaths reported in 2022.1 Globally, South Asia (SA) has the highest OC incidence and mortality rates, with Pakistan ranked fourth (ASIR 9.2) and third (ASMR 5.9). Among Pakistani men, OC is the most common cancer and the second leading cause of cancer-related deaths in both sexes.1
OC exhibits a poor five-year survival of around 50 %–66 %,2,3 which is related mostly to advanced stage disease. Early detection and timely treatment are crucial for reducing OC mortality and morbidity. Advanced stage presentation is strongly associated with delays in diagnosis.4
Several variables have been reported to be related to OC burden.5 Most studies about delays in diagnosis originate from different healthcare systems or high-income settings.3,5,6 Factors contributing to diagnostic delays in South Asia may differ from those in other regions. Lack of awareness about OC symptoms,7,8 and its risk factors,9 has been reported from Pakistan. Sociodemographic variables—such as older age,10,11 and low literacy,10—were also found to be linked with longer delays in Indian studies. Financial constraints7,10,12 and limited access to healthcare facilities13 play a significant role. The latter may be attributed to the large proportion of the South Asian population residing in rural areas, which can hinder access to early screening and treatment.9 Variability in findings may also arise from methodological flaws, such as the absence of a standardized theoretical framework for the design and reporting of time points, as well as the definition and measurement of diagnostic intervals in cancer studies.14
The Aarhus Statement was developed to standardize the pre-diagnostic journey of cancer patients by clearly defining key time points, diagnostic intervals, and methodological approaches. Thus, it enhances the comparability and reliability of research findings.14 Studies in Asia have rarely employed the Aarhus Statement,12,13 limiting the standardization and comparability of OC research on delay in diagnosis.
South Asia has the highest OC burden, with a unique sociocultural background influencing OC diagnosis. However, research on diagnostic delays in South Asia remains scarce. Thus, this study aimed to assess the delay intervals of OC using the Aarhus Statement framework and identify factors contributing to delay in diagnosis in Khyber Pakhtunkhwa (KPK), a province with a predominantly rural population in Pakistan.
Materials and methods
This multi-center cross-sectional study was conducted on consecutive histopathologically confirmed oral squamous cell carcinoma (OSCC) patients (ICD: C00–C06)15 between April and September 2023 in KPK, a province in northwest Pakistan. Patients with recurrent OSCC and those unable to answer the questionnaire were excluded. Data were collected from four hospitals, including three tertiary care centers: Hayatabad Medical Complex (HMC), Institute of Radiotherapy and Nuclear Medicine (IRNUM), and Mardan Medical Complex (MMC); and Sardar Begum Dental College and Hospital (SBDC&H).
Ethical approval for this study was obtained from the Human Research Ethics Committee of the Faculty of Dentistry, Prince of Songkla University, Thailand (EC6602-009), as well as from the respective ethics committees of the participating hospitals: HMC (HMC-QAD-F-00), IRNUM (IRNM/RDPC/2023/27), MMC (327/BKMC), and SBDC&H (approved by hospital authority on May 5, 2023). All study procedures were conducted in accordance with relevant guidelines and regulations, in compliance with the Declaration of Helsinki. Written informed consent was obtained from all participants prior to their enrollment in the study.
A structured questionnaire was developed to investigate patient-related factors. Diagnostic intervals were determined using the Aarhus Statement.14 In the study, appraisal and help-seeking intervals combined are regarded as patient intervals, and the total interval is the sum of the latter and diagnostic intervals (Fig. 1). Appraisal, help-seeking, or diagnostic delays were recorded if they exceeded 30 days.12,16 Patient delay was defined as either appraisal or help-seeking delay. Total delay was determined as the presence of either patient or diagnostic delay. The questionnaire covered sociodemographic factors, prior knowledge, barriers to healthcare access, diagnostic barriers, OSCC clinical history, treatments received before professional consultation, and a timeline of events prior to diagnosis. The questionnaire was translated from English to Urdu, the national language of Pakistan, using the back-translation method to ensure cultural and linguistic appropriateness.17 UA conducted face-to-face interviews to complete the questionnaires, each lasting 15–20 min. Patient responses were verified with referral letters and medical records during the interview. TNM staging and related history were retrieved from individuals' medical records.
Figure 1.
Key events, time intervals, and delays in the diagnosis of oral squamous cell carcinoma (OSCC): in relation to the Aarhus Statement framework.14; HCP, healthcare provider.
The study is part of a large project. The sample size of 152 participants was calculated based on a 5:1 participant-to-item ratio of another part involving Exploratory Factor Analysis (EFA) of a 31-item questionnaire.18
Statistical analysis
The data collected were initially entered into Microsoft Excel (version 2303) for organization and preliminary checks. Descriptive statistics were used to summarize the baseline sociodemographic and clinical characteristics of the study population. Continuous variables related to time intervals, such as appraisal, help-seeking, diagnostic, and patient delays, were analyzed using measures of central tendency (mean, median) and dispersion (standard deviation, interquartile range).
Univariable and multivariable logistic regression analyses examined the associations between various independent variables (sociodemographic factors, cancer characteristics, and healthcare barriers) and different types of delay. Four specific delay outcomes were assessed: appraisal, help-seeking, patient, and diagnostic delay. Univariable analysis assessed each independent variable individually to identify potential associations with the delay outcomes. Statistically significant variables were included in the multivariable models to account for confounding factors. The analysis provided adjusted odds ratios (AOR) and 95 % confidence intervals (CI) to evaluate the strength of the associations between independent variables and outcomes.
The delay outcomes were categorized as binary (yes/no) variables for all analyses. Additionally, independent variables were transformed into binary or ordinal categories where applicable to enhance the analysis. All statistical analyses were conducted using R software (version 4.2.2, R Foundation for Statistical Computing, Vienna, Austria), and statistical significance was set at P < 0.05.
Results
The study included 152 OSCC patients; 69 (45.4 %) were newly diagnosed cases, while 83 (54.6 %) were follow-up cases, diagnosed within the last two years. The subgroup analysis of newly diagnosed and follow-up cases revealed no statistically significant differences in any delay interval. Thus, both groups were included in the statistical analysis. Table 1 summarizes characteristics of the patients. The participants had a male-to-female ratio of 2:1, with a mean age of 53.6 years (range: 21–90 years). The majority received either no formal education or less than 10 years of schooling and had public health coverage. Most of the patients had never had routine dental checkups or only sought dental care when experiencing symptoms. Travel distance and cost of medical care were the primary barriers to accessing healthcare. Women (69.7 %) reported healthcare access challenges more frequently than men (52 %).
Table 1.
Baseline sociodemographic and clinical characteristics of patients with oral squamous cell carcinoma (n = 152).
| Variable | No. of patients (%) |
|---|---|
| Demographic and socioeconomic factors | |
| Sex | |
| Male | 104 (68.4) |
| Female | 48 (31.6) |
| Age | |
| ≤40 | 34 (22.3) |
| 40–60 | 66 (43.4) |
| ≥60 | 52 (34.2) |
| Area of residence | |
| Rural | 110 (72.4) |
| Urban | 42 (27.6) |
| Marital status | |
| Currently married | 124 (81.6) |
| Previously married | 21 (13.8) |
| Never married | 7 (4.6) |
| Employment status | |
| Employed | 92 (60.5) |
| Unemployed | 60 (39.5) |
| Education level | |
| No formal education | 60 (39.5) |
| Formal education | |
| ≤10 years | 62 (40.7) |
| >10 years | 30 (19.7) |
| Average monthly income in Pakistani rupees (PKR)a | |
| No income | 5 (3.3 %) |
| Less than 15,000 PKR | 48 (31.6 %) |
| Between 15,001 and 25,000 PKR | 36 (23.7 %) |
| Between 25,001 and 50,000 PKR | 37 (24.3 %) |
| More than 50,000 PKR | 26 (17.1 %) |
| Health insurance | |
| No | 27 (17.8) |
| Yes | 125 (82.2) |
| Dental checkups | |
| Never had dental checkup | 41 (26.9) |
| Only when symptoms occur | 100 (65.7) |
| At least once per year | 11 (7.2) |
| Disease-related factors | |
| Initial symptoms | |
| Pain | 97 (63.8) |
| Ulcer and other symptoms | 55 (36.2) |
| Cancer stage | |
| Early (I/II) | 39 (25.7) |
| Advance (III/IV) | 113 (74.3) |
| Cancer site | |
| Buccal mucosa | 68 (44.7) |
| Tongue and floor of mouth | 40 (26.3) |
| Other parts of lip and oral cavity | 44 (28.9) |
| Healthcare accessibility and alternative treatment | |
| Convenience to receive medical care | |
| Convenient | 65 (42.8) |
| Inconvenient | 87 (57.2) |
| Treatment received before HCP consultationb | 113 (74.3) |
| Over-the-counter medication | 112 (99.1) |
| T&CMc | 99 (87.6) |
| Faith healing | 71 (62.8) |
| Home remedies | 31 (27.4) |
| Homeopathy | 31 (27.4) |
| Religious verses | 22 (19.4) |
| Hakeem/Tabeeb | 18 (16.0) |
| Delay in HCP consultation despite not seeking T&CMc | 39 (25.7) |
| Waiting for spontaneous healing | 32 (82.0) |
| Observing the progress of the symptoms | 22 (56.4) |
| Consulting with friends and family | 9 (23.0) |
HCP, healthcare provider; PKR, Pakistani rupees; T&CM, traditional and complementary medicine.
Exchange rate in September 2023: 280 PKR per 1 US dollars.
Participants could provide more than one response.
T&CM encompasses various modalities, including faith healing (spiritual or religious rituals conducted by faith healers), home remedies (utilization of natural substances for self-treatment), homeopathy (an alternative medical system based on highly diluted substances derived from plants, minerals, or animal sources to stimulate the body's self-healing mechanisms), religious verses (recitation of Quranic verses for healing), and Hakeem/Tabeeb (a traditional Greco-Arabic medical system incorporating herbal formulations, dietary modifications, and physical therapies for holistic healing).
The majority of the patients sought treatment, including over-the-counter medications (73.6 %) and Traditional and Complementary Medicine (T&CM) therapies (65 %), prior to visiting healthcare providers (HCPs). For the latter, faith healing was the most common therapeutic approach.
HCPs provided appropriate initial treatments to 73.6 % of patients, including a prompt biopsy (12.5 %), scheduling a biopsy for the next visit (15.8 %), or referral to a specialist (45.4 %). The majority of patients (76 %) underwent a biopsy within the first four HCP visits. Additionally, over half (58.6 %) received a biopsy within one month of initial contact, while 18.4 % had their biopsy during the second month.
Patient delays were reported in 116 patients (76.3 %), with 99 experiencing appraisal delays, 37 reporting help-seeking delays, and 20 experiencing both. Diagnostic delays were observed in 78 patients (51.3 %), of whom 64 had both patient and diagnostic delays. The median appraisal interval was 61 days, accounting for the largest portion of the patient interval (median: 89 days). The patient interval was three times longer than the diagnostic interval, making it the primary contributor to the total delay (Table 2). Patient delay ranged from 0 to 1067 days, while total delay ranged from 16 to 1444 days.
Table 2.
Overview of the time intervals in the diagnosis of oral squamous cell carcinoma (n = 152).
| Time intervals (days) | Mean | SD | Q1 | Median | Q3 | Range |
|---|---|---|---|---|---|---|
| Appraisal interval | 114.6 | 179.6 | 16 | 61 | 123 | 0–1067 |
| Help-seeking interval | 42.3 | 128.6 | 0 | 0 | 18 | 0–974 |
| Patient interval | 156.9 | 210.3 | 31 | 89 | 181 | 0–1067 |
| Diagnostic interval | 63.6 | 102.6 | 15 | 32 | 62 | 4–778 |
| Total interval | 220.6 | 245.7 | 72 | 135 | 265 | 16–1444 |
SD, standard deviation; Q1, quartile 1 (25th percentile); Q3, quartile 3 (75th percentile).
Multivariable analysis identified several significant factors associated with delay in OSCC diagnosis. Appraisal delay was linked to never visiting the dentist or visiting only when experiencing symptoms (AOR: 11.04, CI: 2.29–81.53), advanced stage OSCC (AOR: 5.42, CI: 2.35–13.03), and rural residence (AOR: 3.99, CI: 1.75–9.35) (Table 3). Help-seeking delay was related to reliance on home remedies (AOR: 5.74, CI: 2.35–14.46) and the use of homeopathy (AOR: 4.72, CI: 1.90–11.91) (Table 4). Patient delay was also associated with advanced stage OSCC (AOR: 7.73, CI: 3.28–19.12) and rural residence (AOR: 3.91, CI: 1.62–9.69) (Table 5).
Table 3.
Association of appraisal delay with characteristics of the oral squamous cell carcinoma patients.
| Variable | Appraisal delaya n (row %) |
Crude odds ratio |
Adjusted odds ratio |
|||
|---|---|---|---|---|---|---|
| Yes | No | COR (95 % CI) | P-value | AOR (95 % CI) | P-value | |
| Overall | 99 (65.1) | 53 (34.9) | ||||
| Age | ||||||
| <53 | 39 (55.7) | 31 (44.3) | Ref | 0.025 | ||
| ≥ 53 | 60 (73.2) | 22 (26.8) | 2.16 (1.10–4.31) | |||
| Area of residence | ||||||
| Urban | 18 (42.9) | 24 (57.1) | Ref | <0.001 | Ref | 0.001 |
| Rural | 81 (73.6) | 29 (26.4) | 3.72 (1.78–7.94) | 3.99 (1.75–9.35) | ||
| Occupation | ||||||
| Employed | 53 (57.6) | 39 (42.4) | Ref | 0.017 | ||
| Non-employed | 46 (76.7) | 14 (23.3) | 2.42 (1.19–5.13) | |||
| Level of education | ||||||
| >10 years | 14 (46.7) | 16 (53.3) | Ref | 0.020 | ||
| ≤10 years | 85 (69.7) | 37 (30.3) | 2.62 (1.16–6.0) | |||
| Knowledge of oral cancer before diagnosis | ||||||
| Yes | 7 (33.3) | 14 (66.7) | Ref | 0.001 | ||
| No | 92 (70.2) | 39 (29.8) | 4.71 (1.81–13.30) | |||
| Frequency of dental checkup | ||||||
| At least one visit per year | 2 (18.2) | 9 (81.8) | Ref | 0.004 | Ref | 0.005 |
| Never or only when having symptoms | 97 (68.8) | 44 (31.2) | 9.92 (2.43–66.86) | 11.04 (2.29–81.53) | ||
| Last dental checkup | ||||||
| Checkup within last 1 year | 16 (43.2) | 21 (56.8) | Ref | 0.001 | ||
| Never had checkup or long time since last checkup | 83 (72.2) | 32 (27.8) | 3.40 (0.39–1.45) | |||
| Cancer stage | ||||||
| Early | 14 (35.9) | 25 (64.1) | Ref | <0.001 | Ref | <0.001 |
| Advance | 85 (75.2) | 28 (24.8) | 5.42 (2.51–12.11) | 5.42 (2.35–13.03) | ||
| Healthcare accessibility | ||||||
| Convenient | 35 (53.0) | 30 (46.0) | Ref | 0.012 | ||
| Inconvenient | 64 (73.6) | 23 (26.4) | 2.38 (1.21–4.76) | |||
| First HCP consultation | ||||||
| Dentist | 19 (43.2) | 25 (56.8) | Ref | 0.029 | ||
| Doctor | 70 (71.4) | 28 (28.6) | 2.15 (1.08–4.32) | |||
| Number of biopsy visits | ||||||
| ≤2 | 29 (51.8) | 27 (48.2) | Ref | 0.009 | ||
| >2 | 70 (72.9) | 26 (27.1) | 2.50 (1.26–5.04) | |||
| Perception of spontaneous healing | ||||||
| No | 73 (60.8) | 47 (39.2) | Ref | 0.036 | ||
| Yes | 26 (81.3) | 6 (18.7) | 2.78 (1.12–7.94) | |||
| Initial symptoms | ||||||
| Red, white patch | 28 (53.8) | 24 (46.2) | Ref | 0.036 | ||
| Other symptoms | 71 (71.0) | 29 (29.0) | 2.09 (1.04–4.22) | |||
AOR, adjusted odds ratio; COR, crude odds ratio; CI, confidence interval; HCP, healthcare provider; T&CM, traditional and complementary medicine.
Appraisal delay was recorded if it exceeded 30 days.
Table 4.
Association of help-seeking delay with characteristics of the oral squamous cell carcinoma patients.
| Variable | Help-seeking delay n (row %)a |
Crude odds ratio |
Adjusted odds ratio |
|||
|---|---|---|---|---|---|---|
| Yes | No | COR (95 % CI) | P-value | AOR (95 % CI) | P-value | |
| Overall | 37 (24.3) | 115 (75.7) | ||||
| Cancer stage | ||||||
| Early | 4 (10.3) | 35 (89.7) | Ref | 0.023 | ||
| Advance | 33 (29.2) | 80 (70.8) | 3.60 (1.31–12.77) | |||
| Reasons for delay in HCP consultation | ||||||
| Perception of spontaneous healing | ||||||
| No | 34 (28.3) | 86 (71.7) | Ref | 0.035 | ||
| Yes | 3 (9.4) | 29 (90.6) | 3.82 (1.24–16.69) | |||
| Over the counter medication | ||||||
| No | 4 (10.0) | 36 (90.0) | Ref | 0.019 | ||
| Yes | 33 (29.5) | 79 (70.5) | 3.75 (1.36–13.30) | |||
| Home remediesb | ||||||
| No | 20 (16.5) | 101 (83.5) | Ref | <0.001 | Ref | <0.001 |
| Yes | 17 (54.8) | 14 (45.2) | 6.13 (2.63–14.68) | 5.74 (2.35–14.46) | ||
| Homeopathyc | ||||||
| No | 21 (17.4) | 100 (82.6) | Ref | <0.001 | Ref | <0.001 |
| Yes | 16 (51.6) | 15 (48.4) | 5.08 (2.18–12.01) | 4.72 (1.90–11.91) | ||
| Hakeem/Tabeebd | ||||||
| No | 29 (21.7) | 105 (78.3) | Ref | 0.040 | ||
| Yes | 8 (44.4) | 10 (55.6) | 2.90 (0.18–0.41) | |||
| Faith healinge | ||||||
| No | 11 (15.5) | 60 (84.5) | Ref | 0.019 | ||
| Yes | 26 (32.1) | 55 (67.9) | 2.57 (1.19–5.89) | |||
AOR, adjusted odds ratio; COR, crude odds ratio; CI, confidence interval; HCP, healthcare provider; T&CM, traditional and complementary medicine.
Help-seeking delay was recorded if it exceeded 30 days.
Home remedies:utilization of natural substances for self-treatment.
Homeopathy: an alternative medical system based on highly diluted substances derived from plants, minerals, or animal sources to stimulate the body's self-healing mechanisms.
Hakeem/Tabeeb: a traditional Greco-Arabic medical system incorporating herbal formulations, dietary modifications, and physical therapies for holistic healing.
Faith healing (spiritual or religious rituals conducted by faith healers.
Table 5.
Association of patient delay with characteristics of the oral squamous cell carcinoma patients.
| Variable | Patient delaya n (row %) |
Crude odds ratio |
Adjusted odds ratio |
|||
|---|---|---|---|---|---|---|
| Yes | No | COR (95 % CI) | P-value | AOR (95 % CI) | P-value | |
| Overall | 116 (76.3) | 36 (23.7) | ||||
| Age | ||||||
| <53 | 47 (67.1) | 23 (32.9) | Ref | 0.015 | ||
| ≥ 53 | 69 (84.1) | 13 (15.9) | 2.59 (1.21–5.76) | |||
| Area of residence | ||||||
| Urban | 24 (57.1) | 18 (42.9) | Ref | <0.001 | Ref | 0.002 |
| Rural | 92 (83.6) | 18 (16.4) | 3.83 (1.73–8.55) | 3.91 (1.62–9.69) | ||
| Occupation | ||||||
| Employed | 65 (74.7) | 22 (25.3) | Ref | 0.045 | ||
| Non-employed | 51 (85.0) | 9 (15.0) | 2.35 (1.04–5.70) | |||
| Level of education | ||||||
| >10 years | 16 (53.3) | 14 (46.7) | Ref | 0.001 | ||
| ≤10 years | 100 (82.0) | 22 (18.0) | 3.97 (1.68–9.40) | |||
| Knowledge of oral cancer before diagnosis | ||||||
| Yes | 10 (47.6) | 11 (52.4) | Ref | 0.001 | ||
| No | 106 (80.9) | 25 (19.1) | 4.66 (1.78–12.41) | |||
| Frequency of dental checkup | ||||||
| At least 1 visit per year | 4 (36.4) | 7 (63.6) | Ref | 0.003 | ||
| Never or only when having symptoms | 112 (79.4) | 29 (20.6) | 6.75 (1.91–27.29) | |||
| Last dental checkup | ||||||
| Checkup within last 1 year | 20 (54.1) | 17 (45.9) | Ref | <0.001 | ||
| Never had checkup or long time since last checkup | 96 (83.5) | 19 (16.5) | 4.29 (1.90–9.77) | |||
| Cancer stage | ||||||
| Early | 18 (46.2) | 21 (53.8) | Ref | <0.001 | Ref | <0.001 |
| Advance | 98 (86.7) | 15 (13.3) | 7.62 (3.36–17.90) | 7.73 (3.28–19.12) | ||
| Healthcare accessibility | ||||||
| Convenient | 72 (82.8) | 15 (17.2) | Ref | 0.032 | ||
| Inconvenient | 44 (67.7) | 21 (32.3) | 2.29 (1.07–4.97) | |||
| First HCP consultation | ||||||
| Dentist | 35 (64.8) | 19 (35.2) | Ref | 0.014 | ||
| Doctor | 81 (82.7) | 17 (17.3) | 2.58 (1.20–5.61) | |||
| Travel for medical care | ||||||
| Convenient | 45 (68.2) | 21 (31.8) | Ref | 0.041 | ||
| Inconvenient | 71 (82.6) | 15 (17.4) | 2.20 (1.03–4.79) | |||
| Health condition prevented medical access | ||||||
| No | 73 (69.5) | 32 (30.5) | Ref | 0.005 | ||
| Yes | 43 (91.5) | 4 (8.5) | 4.71 (1.72–16.62) | |||
| Referral to specialist on first HCP consultation | ||||||
| Yes | 58 (69.9) | 25 (30.1) | Ref | 0.043 | ||
| No | 58 (84.1) | 11 (15.9) | 2.27 (1.04–5.20) | |||
| Appointment for biopsy on second visit | ||||||
| No | 102 (79.7) | 26 (20.3) | Ref | 0.027 | ||
| Yes | 14 (58.3) | 10 (41.7) | 2.80 (1.09–7.00) | |||
AOR, adjusted odds ratio; COR, crude odds ratio; CI, confidence interval; HCP, healthcare provider.
Patient delay was recorded with either appraisal or help-seeking delay.
Diagnostic delay was associated with a lack of prior knowledge of OC (AOR: 7.33, CI: 1.30–51.74), more than two visits to HCPs prior to undergoing a biopsy (AOR: 52.88, CI: 1.50–270.88), and initial treatment with analgesics (AOR: 13.37, CI: 3.68–60.99) or antimicrobials (AOR: 3.95, CI: 1.06–18.23) (Table 6).
Table 6.
Association of diagnostic delay with characteristics of the oral squamous cell carcinoma patients.
| Variable | Diagnostic delaya n (row %) |
Crude odds ratio |
Adjusted odds ratio |
|||
|---|---|---|---|---|---|---|
| Yes | No | COR (95 % CI) | P-value | AOR (95 % CI) | P-value | |
| Overall | 78 (51.3) | 74 (48.7) | ||||
| Area of residence | ||||||
| Urban | 13 (30.9) | 29 (69.1) | Ref | 0.002 | ||
| Rural | 65 (59.1) | 45 (40.9) | 3.22 (1.53–7.04) | |||
| Knowledge of oral cancer before diagnosis | ||||||
| Yes | 3 (14.3) | 18 (85.7) | Ref | 0.001 | Ref | 0.03 |
| No | 75 (57.3) | 56 (42.7) | 8.03 (2.56–35.50) | 7.33 (1.30–51.74) | ||
| Health insurance | ||||||
| Yes | 20 (23.0) | 67 (77.0) | Ref | 0.011 | ||
| No | 58 (89.2) | 7 (10.8) | 3.30 (1.35–8.92) | |||
| Cancer stage | ||||||
| Early | 13 (33.3) | 26 (66.7) | Ref | 0.010 | ||
| Advance | 65 (57.5) | 48 (42.5) | 2.70 (1.28–5.95) | |||
| Cancer site | ||||||
| Tongue | 72 (55.0) | 59 (45.0) | Ref | 0.030 | ||
| Oral cavity | 6 (28.6) | 15 (71.4) | 3.05 (1.16–9.00) | |||
| Healthcare accessibility | ||||||
| Convenient | 23 (35.4) | 42 (64.6) | Ref | <0.001 | ||
| Inconvenient | 55 (63.2) | 32 (36.8) | 3.13 (1.62–6.20) | |||
| First HCP consultation | ||||||
| Dentist | 18 (33.3) | 36 (66.7) | Ref | 0.001 | ||
| Doctor | 60 (61.2) | 38 (38.8) | 3.15 (1.59–6.44) | |||
| Cost of travel for medical care | ||||||
| Affordable | 28 (38.9) | 44 (61.1) | Ref | 0.003 | ||
| Unaffordable | 50 (62.5) | 30 (37.5) | 2.61 (1.36–5.09) | |||
| Distance and time of travel for medical care | ||||||
| Convenient | 23 (34.8) | 43 (65.2) | Ref | <0.001 | ||
| Inconvenient | 55 (63.9) | 31 (36.1) | 3.31 (1.71–6.57) | |||
| Health condition prevented medical access | ||||||
| No | 47 (44.8) | 58 (55.2) | Ref | 0.017 | ||
| Yes | 31 (65.9) | 16 (34.1) | 2.39 (1.18–4.97) | |||
| Referral to specialist on first HCP consultation | ||||||
| Yes | 28 (40.6) | 41 (59.4) | Ref | 0.016 | ||
| No | 50 (60.2) | 33 (39.8) | 2.21 (1.16–4.29) | |||
| Homeopathy | ||||||
| No | 57 (47.1) | 64 (52.9) | Ref | 0.043 | ||
| Yes | 21 (67.7) | 10 (32.3) | 2.35 (1.04–5.62) | |||
| Faith healing | ||||||
| No | 30 (42.3) | 41 (57.7) | Ref | 0.037 | ||
| Yes | 48 (59.3) | 33 (40.7) | 1.98 (1.04–3.82) | |||
| Number of biopsy visits | ||||||
| ≤2 | 3 (5.4) | 53 (94.6) | Ref | <0.001 | Ref | <0.001 |
| >2 | 75 (78.1) | 21 (21.9) | 63.09 (20.63–277.71) | 52.88 (1.50–270.88) | ||
| Proper treatment on first HCP consultation | ||||||
| Yes | 43 (38.4) | 69 (61.6) | Ref | <0.001 | ||
| No | 35 (87.5) | 5 (12.5) | 6.64 (3.26–14.14) | |||
| Antimicrobial treatment on first HCP consultation | ||||||
| No | 42 (44.2) | 53 (55.8) | Ref | 0.024 | Ref | 0.053 |
| Yes | 36 (63.2) | 21 (36.8) | 2.16 (1.11–4.29) | 3.95 (1.06–18.23) | ||
| Analgesic treatment on first HCP consultation | ||||||
| No | 19 (26.8) | 52 (73.2) | Ref | <0.001 | Ref | <0.001 |
| Yes | 59 (72.8) | 22 (27.2) | 7.33 (3.64–15.38) | 13.37 (3.68–60.99) | ||
| Reassurance of benign lesion on first HCP consultation | ||||||
| No | 59 (44.7) | 73 (55.3) | Ref | 0.002 | ||
| Yes | 19 (95.0) | 1 (5.0) | 23.50 (4.66–428.55) | |||
| Biopsy on first HCP consultation | ||||||
| No | 1 (5.3) | 18 (94.7) | Ref | 0.002 | ||
| Yes | 77 (57.9) | 56 (42.1) | 24.74 (4.88–451.82) | |||
| Utilization of T&CM prior to HCP consultation | ||||||
| No | 62 (47.3) | 69 (52.7) | Ref | 0.019 | ||
| Yes | 16 (76.2) | 5 (23.8) | 3.56 (1.30–11.40) | |||
AOR, adjusted odds ratio; COR, crude odds ratio; CI, confidence interval; HCP, healthcare provider; T&CM, traditional and complementary medicine.
Diagnostic delay was recorded if it exceeded 30 days.
Discussion
The present study systematically assessed delays in the diagnosis of OC, highlighting aspects of early detection in low-resource and culturally distinct settings in South Asia. By evaluating appraisal, help-seeking, patient, and diagnostic intervals independently, the study identifies delay-specific factors, providing more nuanced insights than previous research that often assessed delay as a single composite measure. Although T&CM is common in this region, the current study is the first to report its association, specifically homeopathy and faith healing, with help-seeking delay. Rural residence and lack of patient knowledge were also among the most notable factors. Appraisal and diagnostic delays were the primary contributors to significant delays in diagnosis. The variability in the definitions of delay and the examined variables complicates the comparison of outcomes across research.
Advanced stage diagnosis was observed in 74 % of patients, aligning with the range (58 %–91 %) reported in South Asian studies.10,19 In contrast, significantly lower rates (33 %–40 %) have been documented in high-income countries (HICs).20,21 These findings highlight the pressing need for targeted interventions to reduce patient intervals in lower-middle income countries (LMICs), enabling earlier detection and better survival outcomes.
Most studies combine appraisal and help-seeking delays into a single patient interval. In this study, the median patient interval of three months is consistent with the 90–92 day range reported in South Asia.9,13 This duration is slightly longer than the 75-day median reported for other LMICs and nearly three times the one-month average for HICs as reported in a meta-analysis study.3 The median diagnostic interval in this study was 32 days, aligning closely with the 35-day average reported across both LMICs and HICs.3 The income level of a country seems to affect patient delay but not diagnostic delay.
Reducing appraisal delay is crucial, as it constitutes major part of patient delay. Appraisal delay was significantly associated with rural residence, the absence of routine dental checkups, and advanced stage of disease. Rural residence and advanced stage diagnosis were also associated with patient delay, with rural residence having four times the odds of experiencing delays than their urban counterparts. Similar findings have been reported in other South Asian studies.9,22 These prolonged delays in rural Pakistan reflect deeper socioeconomic disparities, limited awareness of early OC symptoms, and systemic barriers such as inadequate healthcare access, transportation challenges, and financial hardships. Similar trends have been reported in other rural South Asian settings.9,23
Regular dental visits offer the potential for early, and often incidental, detection of OC through routine screenings, even during asymptomatic phases.24 Nevertheless, this study found that the absence of consistent dental examinations was a major contributor to appraisal delays, reinforcing similar findings from an Indian study.12 This may serve as an explanation for the correlation between advanced stage disease at the time of diagnosis and both appraisal and patient delay. It is important to consider that the two findings may be triggered by residing in a rural area.
T&CM practices are prevalent among cancer patients in South Asia, such as Pakistan, India and Nepal.25 The use of T&CM emerged as a significant factor contributing to help-seeking delays in this study. Other studies from Pakistan also reported the use of homeopathy and spiritual healing among OC patients.7,26 T&CM use is deeply embedded in Pakistan's cultural landscape, with reported prevalence ranging from 51 % to 70 %.27,28 In the current study, 65 % of OC patients reported using one or more forms of T&CM prior to consulting HCPs. This behavior likely reflects not only cultural preferences and the perceived non-toxicity of T&CM, but also barriers such as limited access to healthcare, workforce shortages, and affordability issues.26,27 Importantly, the observed association between the use of home remedies and homeopathy and help-seeking delay is a novel finding. This may encourage future research to systematically assess T&CM use as a potential contributor to delay in diagnosis in South Asian settings.
After the implementation of Universal Health Coverage (UHC), comparative studies of diagnosis delays have revealed that traditional medication is no longer a significant factor in both patient and total delays of OC.6,29 Systemic reforms that enhance healthcare accessibility may mitigate health seeking delays in comparable environments.
Both patients and HCPs are responsible for diagnostic delays. Patients' lack of awareness about OC symptoms prior to diagnosis was associated with a seven-fold increase in the odds of delay. Studies conducted in South Asia have consistently reported limited patient awareness of OC symptoms.7,8,12 This aligns with systematic reviews, which link patients’ insufficient knowledge of OC signs and symptoms to delayed diagnosis.5,6 Patients' limited understanding of the disease and its severity may lead to no show for follow-up care, further prolonging the diagnostic process.
Improper initial treatments, such as prescribing analgesics or antibiotics, by HCPs significantly increased the likelihood of diagnostic delay. Several studies from South Asia have reported low clinical suspicion that results in frequent misdiagnosis of OC by HCPs.9,11,12 A systematic review highlighted HCPs’ challenges in recognizing early OC lesions, often resulting in misdiagnoses and inappropriate treatment.5 Additionally, needing more than two visits to perform a biopsy further contributed to delays, likely due to initial misdiagnoses, patients failing to follow up, or concurrent use of alternative treatments.
In the study, some variables, such as “frequency of dental checkup,” “knowledge of OC before diagnosis,” and “number of biopsy visits,” exhibit wide confidence intervals. This observation is likely due to some comparison groups having very low prevalence compared to another group. This situation decreased the statistical power of the regression models.
This study has several limitations. First, it relied on patient recall for symptom onset and healthcare interactions, which may introduce recall bias, particularly in estimating delay durations. To mitigate this, responses regarding diagnostic timelines were corroborated with referral letters and medical records, and accompanying persons were allowed to assist with recall. Additionally, the study focused only on delays up to diagnosis and did not include the pre-treatment interval.
This study contributes to the limited literature from LMICs by applying the Aarhus Statement framework to define and analyze diagnostic delays in OC. By assessing appraisal, help-seeking, patient, and diagnostic intervals separately, the study identifies delay-specific factors, offering more nuanced insights compared to previous research that often assessed delay as a single composite measure.
The delay in OC diagnosis observed in this study reflects a complex interplay of cultural, systemic, and individual barriers. While rural healthcare disparities and the prevalence of T&CM usage contribute significantly to prolonged delays, the findings also emphasize the importance of strengthening healthcare infrastructure and improving public awareness. By addressing these gaps through targeted interventions, such as enhanced healthcare access in rural areas, HCPs training on early OC detection, and tailored education campaigns, there is an opportunity to mitigate delays and improve survival outcomes.
Declaration of competing interest
The authors have no conflicts of interest relevant to this article.
Acknowledgments
The study was supported by the Faculty of Dentistry and Graduate School, Prince of Songkla University, Thailand. The authors also extend their sincere gratitude to Hayatabad Medical Complex (HMC), Institute of Radiotherapy and Nuclear Medicine (IRNUM), Mardan Medical Complex (MMC), and Sardar Begum Dental College and Hospital (SBDC&H), Peshawar, Pakistan, for their generous support and collaboration in facilitating data collection for this study.
References
- 1.Ferlay J., Ervik M., Lam F., et al. International Agency for Research on Cancer; Lyon, France: 2024. Global cancer observatory: cancer today (version 1.1)https://gco.iarc.who.int/today Available at: Date accessed. [Google Scholar]
- 2.Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45:309–316. doi: 10.1016/j.oraloncology.2008.06.002. [DOI] [PubMed] [Google Scholar]
- 3.Fernández-Martínez N.F., Petrova D., Špacírová Z., et al. The duration of intervals on the oral cancer care pathway and implications for survival: a systematic review and meta-analysis. Front Public Health. 2023;11 doi: 10.3389/fpubh.2023.1183244. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.González-Moles M.A., Aguilar-Ruiz M., Ramos-García P. Challenges in the early diagnosis of oral cancer, evidence gaps and strategies for improvement: a scoping review of systematic reviews. Cancers. 2022;14:4967. doi: 10.3390/cancers14194967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Lima A.M., Meira I.A., Soares M.S., Bonan P.R., Mélo C.B., Piagge C.S. Delay in diagnosis of oral cancer: a systematic review. Med Oral Patol Oral Cir Bucal. 2021;26:e815–e824. doi: 10.4317/medoral.24808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Kerdpon D., Jantharapattana K., Sriplung H. Factors related to diagnostic delay of oral squamous cell carcinoma in southern Thailand: revisited. Oral Dis. 2018;24:347–354. doi: 10.1111/odi.12757. [DOI] [PubMed] [Google Scholar]
- 7.Saleem Z., Abbas S.A., Nadeem F., Majeed M.M. The habits and reasons of delayed presentation of patients with oral cancer at a tertiary care hospital of a third world country. PJPH. 2018;8:165–169. [Google Scholar]
- 8.Basharat S., Shaikh B.T., Rashid H.U., Rashid M. Health seeking behavior, delayed presentation and its impact among oral cancer patients in Pakistan: a retrospective qualitative study. BMC Health Serv Res. 2019;19:715. doi: 10.1186/s12913-019-4521-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Swaminathan D., George N.A., Thomas S., Iype E.M. Factors associated with delay in diagnosis of oral cancers. Cancer Treat Res Commun. 2024;40 doi: 10.1016/j.ctarc.2024.100831. [DOI] [PubMed] [Google Scholar]
- 10.Bhattacharyya P., Mukherjee D., Barman S., Dey T.K., Biswas J. Factors responsible for the diagnostic delay in oral cancer patients: a hospital-based sociodemographic study in Kolkata. BJOHNS. 2016;24:141–147. [Google Scholar]
- 11.Philip P.M., Kannan S. An inquiry into patient versus health system factors contribution to the diagnostic interval in oral cancer: an early diagnosis study from Kerala, India. ecancermedicalscience. 2024;18:1745. doi: 10.3332/ecancer.2024.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Kuriakose S., Krishnamurthy A., Vinutha R.S., et al. Time intervals and patient-level factors in oral cancer diagnostic pathways: an application of the WHO framework in India. Cancer Epidemiol. 2022;81 doi: 10.1016/j.canep.2022.102283. [DOI] [PubMed] [Google Scholar]
- 13.Philip P.M., Kannan S. Patient interval and associated factors in the diagnostic journey of oral cancer: a hospital-based cross-sectional study from Kerala, India. Asian Pac J Cancer Prev APJCP. 2021;22:3143–3149. doi: 10.31557/APJCP.2021.22.10.3143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Weller D., Vedsted P., Rubin G., et al. The Aarhus statement: improving design and reporting of studies on early cancer diagnosis. Br J Cancer. 2012;106:1262–1267. doi: 10.1038/bjc.2012.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.World Health Organization . WHO; Geneva, Switzerland: 2019. International statistical classification of diseases and related health problems, 10th revision.https://icd.who.int/browse10/2019/en Available at: Date accessed. [Google Scholar]
- 16.World Health Organization . WHO; Geneva, Switzerland: 2017. Guide to cancer early diagnosis.https://iris.who.int/handle/10665/254500 Available at: Date accessed. [Google Scholar]
- 17.Sousa V.D., Rojjanasrirat W. Translation, adaptation and validation of instruments or scales for use in cross-cultural health care research: a clear and user-friendly guideline. J Eval Clin Pract. 2011;17:268–274. doi: 10.1111/j.1365-2753.2010.01434.x. [DOI] [PubMed] [Google Scholar]
- 18.Costello A.B., Osborne J.W. Best practices in exploratory factor analysis: four recommendations for getting the most from your analysis. Practical Assess Res Eval. 2005;10:7. [Google Scholar]
- 19.Mahmood N., Hanif M., Ahmed A., Jamal Q., Saqib S., Khan A. Impact of age at diagnosis on clinicopathological outcomes of oral squamous cell carcinoma patients. Pakistan J Med Sci. 2018;34:595–599. doi: 10.12669/pjms.343.14086. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Ariyoshi Y., Shimahara M., Omura K., et al. Epidemiological study of malignant tumors in the oral and maxillofacial region: survey of member institutions of the Japanese Society of Oral and Maxillofacial Surgeons. 2002. Int J Clin Oncol. 2008;13:220–228. doi: 10.1007/s10147-007-0756-9. [DOI] [PubMed] [Google Scholar]
- 21.Tsai E., Walker B., Wu S.C. Can oral cancer screening reduce late-stage diagnosis, treatment delay and mortality? A population-based study in Taiwan. BMJ Open. 2024;14 doi: 10.1136/bmjopen-2024-086588. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Akram M., Siddiqui S.A., Karimi A.M. Patient related factors associated with delayed reporting in oral cavity and oropharyngeal cancer. Int J Prev Med. 2014;5:915–919. [PMC free article] [PubMed] [Google Scholar]
- 23.Kumar S., Heller R.F., Pandey U., Tewari V., Bala N., Oanh K.T. Delay in presentation of oral cancer: a multifactor analytical study. Natl Med J India. 2001;14:13–17. [PubMed] [Google Scholar]
- 24.Gigliotti J., Madathil S., Makhoul N. Delays in oral cavity cancer. Int J Oral Maxillofac Surg. 2019;48:1131–1137. doi: 10.1016/j.ijom.2019.02.015. [DOI] [PubMed] [Google Scholar]
- 25.Choi S., Kunwor S.K., Im H., et al. Traditional and complementary medicine use among cancer patients in asian countries: a systematic review and meta-analysis. Cancers (Basel) 2024;16:3130. doi: 10.3390/cancers16183130. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Khokhar M.A., Niaz M.O., Aslam A., et al. Pakistan Oral Cancer Collaborative: analyzing barriers and obstacles to oral cancer diagnosis, treatment, and prevention in Pakistan. Oral Surg Oral Med Oral Pathol Oral Radiol. 2021;132:312–319. doi: 10.1016/j.oooo.2021.04.058. [DOI] [PubMed] [Google Scholar]
- 27.Shaikh S.H., Malik F., James H., Abdul H. Trends in the use of complementary and alternative medicine in Pakistan: a population-based survey. J Alternative Compl Med. 2009;15:545–550. doi: 10.1089/acm.2008.0232. [DOI] [PubMed] [Google Scholar]
- 28.World Health Organization . WHO; Geneva, Switzerland: 2019. WHO global report on traditional and complementary medicine 2019.https://iris.who.int/handle/10665/312342 Available at: [Date accessed. [Google Scholar]
- 29.Kerdpon D., Sriplung H. Factors related to delay in diagnosis of oral squamous cell carcinoma in southern Thailand. Oral Oncol. 2001;37:127–131. doi: 10.1016/s1368-8375(00)00072-5. [DOI] [PubMed] [Google Scholar]