Background - Early Diagnosis and Screening

Introduction

Each year, more than 14 million people are diagnosed with cancer, the majority of whom live in low- and middle-income countries (LMICs). The number of deaths due to cancer in LMICs LMICs low- and middle-income countries exceeds those due to HIV/AIDS, tuberculosis and malaria combined.

Approximately two thirds of global cancer deaths are in less developed countries, where case fatality rates are higher due to late-stage presentation and less accessible treatment. The consequences of delays in care and advanced cancer are dire, as the likelihood of death and disability from cancer increases significantly as cancer progresses. It is therefore critical to develop programs to provide access to timely diagnosis and treatment.

Understanding Early Diagnosis and Screening

Early diagnosis is defined as the early identification of cancer in patients who have symptoms of the disease. This contrasts with cancer screening that seeks to identify unrecognized (pre-clinical) cancer or pre-cancerous lesions in an apparently healthy target population. Cancer early diagnosis and screening are both important components of comprehensive cancer control, but are fundamentally different in resource and infrastructure requirements, impact and cost.

When done promptly, cancer may be detected at a potentially curable stage, improving survival and quality of life. There are three steps to early diagnosis:
• Step 1: awareness of cancer symptoms and accessing care;
• Step 2: clinical evaluation, diagnosis and staging; and
• Step 3: access to treatment, including pain relief.

In contrast, screening aims to identify unrecognized cancer or its precursor lesions in an apparently healthy, asymptomatic population by means of tests (e.g. HPV assay), examinations (e.g. VIA visual inspection with acetic acid), imaging (e.g. mammography) or other procedures that can be applied rapidly and accessed widely by the target population.

Barriers to early diagnosis are generally analogous to those in the cancer screening process and include limited access to diagnostic tests and pathology; poor follow-up and coordination; inaccessible high-quality, timely treatment; and financial obstacles. Policies and programmes to overcome these barriers should focus on improving early diagnosis, prior to implementing cancer screening when possible.

A situation analysis should be performed prior to planning or scaling-up early diagnosis or screening programmes. The assessment can include effectiveness and costs of current cancer control strategies, current population coverage of services, obstacles to care including delays, financial protection and quality of care.

The overall status of early diagnosis and screening programmes can be assessed in the distribution of cancer stage at diagnosis and trends overtime.

Impact of Early Diagnosis

There is consistent evidence that the early diagnosis of cancer, combined with accessible, affordable effective treatment, results in improvements in both the stage of cancer at presentation and mortality from cancer. Over 50% of the decrease in breast cancer mortality in women under age 65 was due to improved early diagnosis and the provision of effective treatment.

It is also well established that reducing delays in care can have a significant impact on improving outcomes. In one study, patients who experienced a short delay (<3 months) experienced an absolute 7% greater likelihood of survival from breast cancer compared with those who had moderate delays (3–6 months) in care.

While improving early diagnosis generally improves outcomes, not all cancer types benefit equally. Cancers that are common, that can be diagnosed at early stages from signs and symptoms and for which early treatment is known to improve the outcome are generally those that benefit most from early diagnosis. Examples include breast, cervical, colorectal and oral cancers.

2018 Interlab Plate Reader Protocol
Protocols/Transformation

Achieving Early Diagnosis

There are three key steps to cancer early diagnosis.

Step 1: Awareness and accessing care Symptom appraisal (period from detecting a bodily change to perceiving a reason to discuss the symptoms with a health-care practitioner); and health-seeking behavior (period from perceiving a need to discuss the symptoms with a health-care practitioner to reaching the health facility for an assessment).

Step 2: Clinical evaluation, diagnosis and staging Accurate clinical diagnosis; diagnostic testing and staging; and referral for treatment. This step is also known as the diagnostic interval.

Step 3: Access to treatment The patient with cancer needs to be able to access high-quality, affordable treatment in a timely manner.

Delays and barriers

Poor health literacy: Lack of awareness about cancer symptoms is common and can result in a prolonged symptom appraisal interval and significant delays in seeking care.

Cancer stigma: Cancer stigma is a sense of devaluation by individuals or communities related to cancer patients. Patients may be embarrassed about the symptoms or fear the financial or personal impact of receiving care for cancer.

Limited access to primary care: Access to primary care is critical for early diagnosis by enabling a timely diagnosis. Barriers to seeking primary care may be related to financial constraints, geographic/transportation obstacles, time-poverty and inflexible working conditions, non-availability of services, sociocultural or gender-related factors, compounded by generally lower health literacy and higher levels of cancer stigma.

Inaccurate clinical assessment and delays in clinical diagnosis: Patient encounters with health-care providers can result in delays in care when they lack diagnostic capacity or are isolated from the health system. Cancer signs and symptoms can be vague, non-specific or difficult to detect. A larger percentage of countries do not have programmes or guidelines to strengthen the early identification of common cancers at the primary care level.

Inaccessible diagnostic testing, pathology and staging: Barriers to or harms from diagnostic tests and pathology can range from inaccessible or unavailable services to overusing tests, depending on resource availability.

Poor coordination and loss to follow-up: The facility where a clinical diagnosis is made may be different from where the biopsy is obtained, pathology reviewed and/or staging performed. Delays in cancer diagnosis may arise due to poor follow-up, lack of referral pathways and fragmented health services. Less than 50% of low- and middle-income countries currently have clearly defined referral systems for suspected cancer from primary care to secondary and tertiary care.

Financial, geographic and logistical barriers In a significant number of countries, basic treatment services are unavailable. Fear of financial catastrophe is also a major cause of non-attendance for diagnosis, delay and abandonment of treatment among patients with early cancer symptoms. Patients may have to travel long distances to access a facility capable of providing cancer treatment, and longer travel distance has been associated with late presentation.

Sociocultural barriers: Patients may inaccurately believe cancer is incurable or associate cancer treatment with death or pain, resulting in delays in or not pursuing care.

Fig 1. The particle standard curve obtained form the 2nd calibration experiment.

xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx xxx.

The table template is here.

Table 1. Colony forming units per 0.1 OD₆₀₀

samples	dilution factor			CFU/mL
samples	8×10⁴	8×10⁵	8×10⁶	CFU/mL
1.1	TNTC	48	11	3.84E+07
1.2	248	41	10	3.28E+07
1.3	172	54	5	4.32E+07
2.1	TNTC	143	20	1.14E+08
2.2	TNTC	153	25	1.22E+08
2.3	TNTC	151	18	1.21E+08
3.1	TNTC	119	16	9.52E+07
3.2	TNTC	125	19	1.00E+08
3.3	TNTC	89	18	7.12E+07
4.1	TNTC	209	16	1.67E+08
4.2	TNTC	130	17	1.04E+08
4.3	TNTC	164	10	1.31E+08

Section5

XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX XXX