Cervical cancer testing: which tests confirm the diagnosis and help choose treatment

Cervical cancer is a malignant tumor that develops in the tissues of the cervix, the lower part of the uterus that connects to the vagina. In most cases, the disease is associated with long-term infection with oncogenic types of the human papillomavirus, but the path from infection to cancer typically takes years. Therefore, proper screening and timely diagnosis allow for the detection of precancerous changes and early cancer before serious consequences occur. The World Health Organization states that cervical cancer is largely preventable through vaccination against the human papillomavirus and regular screening, and with early detection and prompt treatment, it can be curable. [1]

It's important to immediately distinguish between two different situations: screening and diagnosis. Screening is performed on people without symptoms to detect precancerous changes before symptoms develop; diagnosis is performed when symptoms develop, suspicious screening results appear, or changes in the cervix are visible. The American Cancer Society emphasizes that the HPV test and Pap smear are screening tests, not definitive diagnostic tests: they cannot, by themselves, reliably determine whether cancer is present. [2]

The primary test for confirming cervical cancer is a biopsy, which involves taking a tissue sample and then examining it histologically. Cytology may reveal suspicious cells, a human papillomavirus test may indicate high-risk cells, and a colposcopy can help visualize suspicious areas. However, it is the tissue examined under a microscope that provides definitive confirmation of precancerous or invasive cancer. The American Cancer Society explicitly states that a biopsy is the best way to accurately determine whether an abnormal area is precancerous, invasive cancer, or neither. [3]

Modern cervical cancer diagnosis is no longer limited to a simple Pap smear. It includes symptom assessment, physical examination, HPV testing, cytology, colposcopy, biopsy, endocervical curettage (ECD), sometimes conization, histology, imaging for staging, pretreatment blood tests, and biomarkers to guide drug therapy in advanced, recurrent, or metastatic disease. The National Cancer Institute lists diagnostic procedures as history, physical examination, pelvic examination, cytology, HPV testing, ECD, colposcopy, and biopsy. [4]

A major practical mistake is to look for a "cervical cancer blood test" instead of a proper diagnostic pathway. Complete blood counts, biochemical parameters, and some tumor markers can be useful for assessing general condition, anemia, organ function, preparing for surgery, or monitoring individual patients after treatment, but they do not replace a biopsy and are not suitable for independently ruling out cancer. The Canadian Cancer Society classifies complete blood counts and biochemical parameters as tests that can be ordered in diagnosis and treatment planning, but the primary diagnostic pathway includes physical examination, cytology, human papillomavirus testing, colposcopy, and biopsy. [5]

Survey group	What does it show?	Does cancer itself confirm
Human papillomavirus test	The presence of oncogenic types of the virus	No
Cytological examination	Suspicious cells on the surface of the cervix	No
Colposcopy	Suspicious areas under magnification	No
Biopsy	Tissue structure of the suspicious area	Yes
Histology	Tumor type, depth and growth characteristics	Yes
Blood tests	Anemia, organ function, treatment safety	No
Tumor biomarkers	Possibility of individual medicinal methods	Not primary diagnosis
Visualization	Prevalence of the disease	Does not replace a biopsy

The table illustrates the basic logic: screening tests identify risk, while tissue confirms the diagnosis. Therefore, a positive HPV test does not equal cancer, but a negative or old test should not be reassuring if bleeding, pain, unusual discharge, or a visible cervical tumor are present. [6]

When are tests prescribed for suspected cervical cancer?

An abnormal screening result may prompt testing: a positive test for oncogenic types of human papillomavirus, abnormal cytology, or a combination of these results. Following this result, the physician assesses the individual's risk and decides whether repeat testing, expanded viral typing, dual p16 and Ki-67 staining, colposcopy, or biopsy are needed. Updated screening guidelines adopted in the United States in 2026 explicitly state that additional tests, including cytology, biopsy, colposcopy, expanded genotyping, dual staining, and pathology examination, may be required to complete the screening process. [7]

The second reason is symptoms, even if routine screening has not been performed in a while or was once normal. Common symptoms include bleeding after intercourse, bleeding between periods, bleeding after menopause, unusual watery or foul-smelling discharge, pelvic pain, and pain during intercourse. The National Cancer Institute lists vaginal bleeding, unusual discharge, pelvic pain, pain during intercourse, and postcoital bleeding as possible symptoms of cervical cancer. [8]

The third reason is visible changes in the cervix during a gynecological examination. Sometimes the doctor sees an area that bleeds when touched, has an uneven surface, an ulcerated defect, a dense mass, a suspicious polyp-like growth, or a cervical deformity. In such a situation, cytology alone is not enough: a targeted evaluation is required and, if there is a suspicious area, a biopsy. The American Cancer Society indicates that symptoms, a suspicious cytology result, or a positive HPV test usually require a colposcopy, and if an abnormal area is detected, a biopsy is taken. [9]

The fourth reason is surveillance after treatment for precancerous lesions or previous cervical cancer. For these patients, the surveillance regimen differs from routine screening because the risk of recurrence or new precancerous lesions is higher. The American Society for Colposcopy and Cervical Pathology, in its 2025 practice document, emphasizes that self-collection for HPV testing is intended for asymptomatic individuals in a routine screening situation, and not for surveillance after treatment for precancerous lesions or after abnormal results. [10]

The fifth reason is confirmed invasive cancer, which requires not only diagnostic tests but also staging and treatment selection. After cancer is confirmed, the doctor evaluates the tumor's extent, lymph node status, kidney function, hemoglobin levels, and the possibility of surgery, radiation therapy, chemotherapy, immunotherapy, or targeted therapy. The National Comprehensive Cancer Network, in its 2.2026 guidelines, emphasizes that cervical cancer guidelines include diagnostic testing, staging, surgical principles, and primary treatment for early and advanced stages. [11]

Clinical situation	What tests and procedures are usually needed?
Positive test for human papillomavirus	Cytology, genotyping, colposcopy according to risk
Altered cytology	Colposcopy, biopsy as indicated
Blood after sexual intercourse	Examination, cytology, virus test, colposcopy, biopsy
Postmenopausal bleeding	Cervical examination and exclusion of other sources of blood
Visible suspicious formation	Targeted biopsy
Confirmed cancer	Histology, imaging, blood tests, biomarkers
Recurrence or metastasis	Biopsy of the lesion, PD-L1 protein, other molecular tests as needed

The practical conclusion is simple: if you have symptoms, you need a diagnostic examination, not a "routine screening for peace of mind." Self-sampling for HPV testing can expand access to screening, but if you experience bleeding, pain, suspicious discharge, or post-treatment monitoring, a physician-collected sample and a full in-person evaluation are preferable. [12]

Human papillomavirus test

The human papillomavirus test detects oncogenic types of the virus, which are associated with the development of precancerous changes and cervical cancer. It is not a test for cancer itself; it indicates biological risk, as the prolonged persistence of an oncogenic virus can trigger a chain of cellular changes. The World Health Organization states that cervical cancer is caused by persistent infection with the human papillomavirus, and women living with the human immunodeficiency virus have a six-fold higher risk of developing cervical cancer compared to women without this infection. [13]

In modern screening programs, testing for human papillomavirus (HPV) is becoming increasingly important because it better identifies the high risk of future precancerous changes than cytology alone. The US National Cancer Institute notes that testing for the genetic material of the HPV detects severe cervical dysplasia, and clinical trials demonstrate the superiority of such testing over other screening strategies. [14]

It's important to interpret the test result not as "positive means cancer," but as "positive means next step." For many people, the infection resolves on its own and does not lead to cancer, especially at a young age; therefore, the decision to have a colposcopy depends on age, virus type, cytology, previous results, and individual risk. The National Cancer Institute emphasizes that HPV testing can detect infections that will never lead to dysplasia or cancer, especially in women under 30. [15]

Types 16 and 18 are particularly important because they are associated with the highest risk of severe precancerous changes and cancer. When these types are detected, doctors often refer for colposcopy or more thorough follow-up examination, even when cytology does not appear significantly abnormal. The US National Cancer Institute reports that infection with types 16 and 18 is associated with a significantly increased risk of rapid development of severe cervical intraepithelial neoplasia. [16]

A new important topic is self-collection of specimens for HPV testing. The American Cancer Society, in its 2025 update, stated that self-collected vaginal specimens, collected at home or in a clinic, are acceptable for initial HPV testing in people at average risk, and if such a test is negative, repeat testing is recommended after 3 years; however, physician-collected cervical specimens remain preferred and, if negative, are typically repeated after 5 years. [17]

Test result	What does it usually mean?	What may be required
The virus was not detected	The risk of significant changes is low	Scheduled screening interval
An oncogenic type was detected without specification.	There is an increased risk	Cytology, repeat test or colposcopy according to risk
Type 16 discovered	Higher risk of severe changes	Usually more active follow-up examination
Type 18 discovered	Increased risk, including glandular lesions	More active follow-up examination
Positive self-collected test	Confirmation and routing required	Examination, sample from a doctor, cytology or colposcopy
Positive test in a symptomatic patient	This is not a screening situation.	In-person diagnostics, not just a repeat test

Self-collection should not be used as a way to avoid a doctor's appointment if you have symptoms. The American Society for Colposcopy and Cervical Pathology states that people with symptoms, such as abnormal bleeding, are not candidates for self-collection as part of routine screening, and that a positive self-collection sample requires a speculum examination because a vaginal sample is not collected directly from the cervix. [18]

Cytological smear and liquid cytology

A cytology test, also known as a Pap smear, examines cells taken from the surface of the cervix. The lab evaluates whether the cells appear normal, whether there are signs of inflammation, low- or high-grade precancerous changes, suspicion of cancer, or glandular atypia. The Canadian Cancer Society explains that a cytology test involves examining a small sample of cells from the surface of the cervix under a microscope to determine whether the cells appear normal or abnormal.[19]

Cytology has played a significant role in reducing cervical cancer mortality, but it is not a definitive diagnosis. The US National Cancer Institute states that regular cytology screening reduces cervical cancer incidence and mortality by at least 80% in eligible populations, but abnormal results can lead to additional procedures and sometimes overtreatment of low-grade lesions. [20]

Liquid-based cytology is a type of cytological examination in which cells are placed in a special liquid medium rather than directly applied to a slide. This sample is convenient because it can often be used for additional tests, such as testing for human papillomavirus (HPV) or additional cellular markers, if the laboratory system allows it. The US National Cancer Institute classifies liquid-based technologies separately as cervical screening methods and considers them alongside cytology and HPV testing. [21]

For some cytology results, the doctor may order reflex testing for oncogenic types of human papillomavirus (HPV) or immediately refer the patient for colposcopy. For example, with atypical cells of uncertain significance, a positive HPV test significantly increases the need for further evaluation. The US National Cancer Institute notes that testing for HPV genetic material has proven useful for triaging patients with atypical squamous cells of uncertain significance into those requiring colposcopy. [22]

Cytology is particularly important where primary HPV testing is unavailable or when the clinical situation requires cellular evaluation. However, in cases of visible tumor, recurrent bleeding, a suspicious examination, or high clinical suspicion, a normal cytology result should not preclude a biopsy, as a smear collects cells from the surface and may miss deep-seated or focal lesions. The American Cancer Society emphasizes that cytology and HPV testing cannot reliably determine whether cancer is present, and abnormal or symptomatic situations require further diagnostic testing. [23]

Cytology result	What could it mean?	Typical next step
Normal cytology	No atypical cells were found.	Routine screening by age and risk
Atypical squamous cells of undetermined significance	Weak or unclear changes	Human papillomavirus testing or risk monitoring
Low grade squamous cell lesion	Often associated with a viral infection	Colposcopy or age- and risk-based monitoring
High grade squamous cell lesion	Significant risk of high-grade precancer	Colposcopy and biopsy
Atypical glandular cells	Changes in the cervical canal or endometrium are possible.	In-depth examination
Suspicion of cancer	High probability of serious pathology	Urgent colposcopy and biopsy

Cytological results should always be interpreted in conjunction with age, HPV testing, previous screening history, symptoms, and physical examination. The same cytological result in a young patient without risk factors and in a patient over 50 with bleeding may lead to different treatment strategies. [24]

Double staining for p16 and Ki-67, expanded genotyping and new clarifying tests

Following a positive HPV test, the physician must decide who should be referred for immediate colposcopy and who can safely be advised to remain under observation. For this purpose, clarifying methods are used: cytology, extended viral genotyping, and dual staining for p16 and Ki-67. Updated preventive guidelines published in the US Federal Register in 2026 explicitly list these methods among the additional tests that may be required to complete the screening process. [25]

Expanded genotyping allows us to not simply say "there is an oncogenic virus," but to specify the specific type or group of types detected. This is important because types 16, 18, and 45 have a higher clinical risk than many other oncogenic types and may change the urgency of additional testing. The American Society of Colposcopy and Cervical Pathology, in its 2025 document, describes modern tests that separately report types 16, 18, 45, and other groups of oncogenic virus types. [26]

Dual staining of p16 and Ki-67 looks for signs of disruption of normal cell division control in cells. Simply put, p16 becomes visible when cellular mechanisms are altered by viral transformation, and Ki-67 indicates active cell division; the combination of these features in a single cell is more suggestive of significant precancerous lesions. The National Cancer Institute notes that cytology can be used for triage after initial HPV testing, and triage may be improved by the simultaneous detection of p16 and Ki-67 in the same cell. [27]

These clarifying tests do not replace a biopsy if the risk is already high or a suspicious area is visible during colposcopy. Their purpose is to reduce the number of unnecessary colposcopies while simultaneously not missing those with a higher probability of significant changes. Therefore, the results of double staining or genotyping are useful only in the context of a complete patient history. [28]

New technologies, including automated image analysis and artificial intelligence algorithms, are being explored to assist in triaging results, particularly in mass screening programs. However, for an individual patient, the principle remains the same: a suspicious screening leads to a diagnosis, and a definitive diagnosis requires tissue. The US National Cancer Institute notes that deep learning algorithms are being explored for the automatic recognition of p16 and Ki-67 dual staining, but this is an assistive technology rather than a replacement for the clinical pathway. [29]

Clarifying test	When is it useful?	What helps to solve
Extended genotyping of the virus	Positive test for oncogenic virus	How urgently is a colposcopy needed?
Cytology after a positive viral test	Primary viral screening	Are there any cellular changes?
Double staining of p16 and Ki-67	Unclear risk after viral test	Higher or lower probability of significant precancer
Retesting	Low or intermediate risk	Does the infection persist?
Colposcopy	High risk or symptoms	Where to take a biopsy

The main limitation of all clarifying tests is that they assess probability rather than provide a definitive tissue diagnosis. If a doctor detects a suspicious cervix or there are symptoms of cancer, the algorithm should not be extended by repeat screening tests. [30]

Colposcopy and biopsy

Colposcopy is a magnified examination of the cervix, vagina, and external genitalia using a special optical instrument. During the procedure, the doctor inserts a speculum and applies acetic acid and sometimes other solutions to the cervix to make suspicious areas more visible. The Canadian Cancer Society describes colposcopy as a lighted, magnifying examination performed after an abnormal cytology test, a positive human papillomavirus test, or symptoms of cervical cancer. [31]

Colposcopy alone does not confirm cancer, because the doctor sees the external tissue patterns, vessels, and staining, but does not see the cellular structure the way a pathologist sees it under a microscope. Therefore, if a suspicious area is detected, a biopsy is taken. The American Cancer Society points out that colposcopy allows the abnormal area to be removed in a small fragment and sent to a lab, and a biopsy is the best way to accurately determine precancerous, cancerous, or the absence of both conditions. [32]

A colposcopic biopsy is typically taken with forceps from one or more suspicious areas. The procedure may cause brief pain, cramping, and slight bleeding, but is often performed on an outpatient basis. The American Cancer Society describes a colposcopic biopsy as the removal of a small portion of an abnormal area on the surface of the cervix after examination with a colposcope. [33]

If the transformation zone is poorly visible or the suspected lesion may be located in the cervical canal, endocervical curettage (ECD) is performed. This is a procedure in which cells or tissue are removed from the cervical canal using a special instrument. The National Cancer Institute lists endocervical curettage (ECD) as a procedure used to diagnose cervical cancer. [34]

If a small biopsy reveals severe precancerous tissue, suspects microinvasive cancer, or if the depth and extent of a lesion need to be assessed, a conization may be necessary. Conization involves removing a cone-shaped piece of the cervix, allowing the pathologist to see not only the surface cells but also the depth of the lesion. The American Cancer Society notes that some types of biopsy can completely remove abnormal tissue and, in some cases, serve both diagnostically and therapeutically. [35]

Procedure	What does it give?	When it is especially needed
Colposcopy	Sees suspicious areas under magnification	After an abnormal screening or when symptomatic
Targeted biopsy	Confirms precancer or cancer by tissue	With a visible anomalous zone
Endocervical curettage	Checks the cervical canal	If the risk zone is not fully visible
Conization	Shows the depth of the lesion and the edges	If microinvasion is suspected
Repeat biopsy	Clarifies an unclear or contradictory result	If the symptoms and tests do not match

After a biopsy, it's important to obtain not only the "there is cancer" statement but also a complete pathology report. The histological type, degree of differentiation, depth of invasion, involvement of the vascular-lymphatic spaces, the condition of the margins of the removed fragment, and signs of dissemination are important for treatment. [36]

Histology and immunohistochemistry

A histological examination examines the tissue under a microscope to determine whether precancerous changes, invasive cancer, and the specific type of tumor detected are present. Squamous cell carcinoma is the most common, but adenocarcinoma and other rarer variants can also occur, which may have different prognoses and treatment strategies. The National Cancer Institute emphasizes that the prognosis for cervical cancer depends significantly on the extent of the disease at diagnosis, and early detection with a Pap test and human papillomavirus testing is possible in more than 90% of cases. [37]

For precancerous lesions, the pathologist describes the extent of the lesion, as mild changes are often observed or managed differently than severe ones. For invasive cancer, the pathologist evaluates the tumor type, depth of invasion, lesion size, condition of the margins of the removed tissue, and evidence of invasion of lymphatic or blood vessels. These data help decide whether organ-preserving treatment is sufficient, or whether more extensive surgery, radiation therapy, or a combination of therapies is needed. [38]

Immunohistochemistry is a method that looks for specific proteins in tissue. In the diagnosis of cervical lesions, the p16 protein and Ki-67 index are often important because they help distinguish reactive changes from virus-induced precancerous processes. In complex or unclear cases, immunohistochemistry can help the pathologist clarify the diagnosis, but it does not replace routine microscopic examination of the tissue. [39]

In advanced or recurrent cancer, additional immunohistochemical and molecular tests may be required that are not related to the primary diagnosis but to the choice of drug therapy. For example, programmed death ligand 1 protein, high microsatellite instability features, a defect in the mismatch repair system, and a high tumor mutational burden are examined. The American Cancer Society indicates that pembrolizumab can be used in some advanced cervical cancers after other treatments if the tumor cells have a high level of microsatellite instability, a defect in the repair system, a high tumor mutational burden, or a high level of programmed death ligand 1 protein. [40]

In some situations, testing is performed not on the primary tumor, but on a metastatic or recurrent lesion. This is important because tumor biology can change after treatment, and available fresh material sometimes better reflects current sensitivity to therapy. If tissue is scarce, the physician may consider a repeat biopsy or molecular testing of the available material, but the decision depends on the clinical situation. [41]

What the pathologist writes	Why is this important?
Precancerous or invasive cancer	Separates observation, removal of precancer and treatment of cancer
Squamous cell carcinoma or adenocarcinoma	Affects the forecast and tactics
Depth of invasion	Helps determine the stage and extent of treatment
Tumor size	Important for stage and operation
Vascular-lymphatic invasion	Increases the risk of spread
The edges of the removed tissue	They show whether the lesion has been completely removed.
p16 and Ki-67 protein	They help to clarify the nature of the lesion
Programmed death protein ligand 1	May influence the choice of immunotherapy

Histology answers the question, "What is this tissue process?" and biomarkers answer the question, "What biological features can be used for prognosis or treatment?" Therefore, modern cervical cancer testing should be viewed as a consistent system, not as a single, universal test. [42]

Blood tests and tumor markers

A complete blood count (CBC) does not diagnose cervical cancer, but is often needed in real-world clinical practice. It helps identify anemia during prolonged bleeding and assess white blood cell (WBC) and platelet counts, as well as the patient's overall health before biopsy, surgery, chemotherapy, or radiation therapy. The Canadian Cancer Society includes a CBC in its list of tests that may be ordered for the diagnosis of cervical cancer and treatment planning. [43]

Blood chemistry tests also don't confirm cancer, but they do show how the liver, kidneys, and other systems are functioning. This is especially important before the administration of contrast agents, chemotherapy, platinum-based therapies, pain medications, and other drugs. The Canadian Cancer Society notes that blood chemistry tests can be used to assess organ function and aid in treatment planning. [44]

Tumor markers in cervical cancer have a limited role. For example, squamous cell antigen (SCA) may be elevated in cervical squamous cell carcinoma (SCC) and is sometimes used to assess prognosis or monitor post-treatment in individual patients, but it is not suitable for mass screening and does not replace biopsy. Reviews of SCA note its potential value in monitoring response to radiation therapy or detecting recurrence, but not as a standalone diagnostic test. [45]

Cancer antigen 125 and other markers may be considered in certain cases, such as adenocarcinoma, advanced disease, or differential diagnosis, but their specificity is insufficient. A single elevated marker does not prove cervical cancer, and a normal marker does not rule it out. Studies of tumor markers show a relationship between some indicators and tumor stage and type, but sensitivity and specificity are insufficient for independent diagnosis. [46]

Before treatment, additional tests may be required to check for pregnancy, blood clotting, blood type, infections, kidney function, electrolyte levels, liver function tests, and any associated medical conditions. These tests are not needed to detect cancer, but to safely administer surgery, radiation therapy, chemotherapy, immunotherapy, and pain management. [47]

Blood test	Why is it prescribed?	Can cancer be ruled out?
Complete blood count	Anemia, platelets, inflammatory changes	No
Ferritin and iron metabolism	Evaluation of iron deficiency in bleeding	No
Creatinine and kidney function calculation	Safety of contrast and platinum drugs	No
Liver function tests	Safety of drug treatment	No
Coagulogram	Risk of bleeding and preparation for procedures	No
Squamous cell carcinoma antigen	Sometimes forecast and observation	No
Cancer antigen 125	Sometimes in certain clinical situations	No

If a patient is offered a "blood test for cervical cancer," it's important to clarify what exactly is meant. Blood tests help assess the body's condition and sometimes the progression of the disease, but a diagnosis of cervical cancer is confirmed by tissue taken during a biopsy or surgery. [48]

Imaging after diagnosis confirmation

After invasive cervical cancer is confirmed, the doctor must determine the stage, that is, determine how far the tumor has spread. This can be accomplished using pelvic magnetic resonance imaging, computed tomography (CT), positron emission tomography (PET), ultrasound, radiography, and other methods, depending on the clinical situation. The National Cancer Institute (NCI) recommends staging after diagnosis because information about the extent of the disease is needed to determine treatment. [49]

Magnetic resonance imaging is particularly useful for assessing local spread: tumor size, involvement of the parametrium, vagina, uterine body, and adjacent structures. This helps determine whether surgery is feasible or whether chemoradiation is the best option. The US National Cancer Institute classifies magnetic resonance imaging as a method that can be used in the staging of cervical cancer. [50]

Computed tomography (CT) and positron emission tomography (PET) scans help evaluate lymph nodes, abdominal organs, the chest, and possible distant lesions. These methods do not replace a biopsy, but they can help determine whether the disease is localized, locally advanced, or metastatic. The National Cancer Institute lists CT and PET scans among the procedures that can be used in the staging process. [51]

Imaging is sometimes used after treatment, but not always in the form of regular "whole-body scans." The US National Cancer Institute advises that follow-up should focus on a thorough history, physical examination, and symptom review, with imaging used to evaluate positive findings. [52]

The main mistake is to consider imaging as a substitute for histology. Even if tomography reveals a suspicious nodule or lesion, if possible and clinically necessary, the diagnosis of recurrence or metastasis is confirmed morphologically, especially if this will affect treatment choice. [53]

Method	The main role
Magnetic resonance imaging of the pelvis	Local spread of the tumor
Computed tomography	Lymph nodes, chest, abdomen
Positron emission tomography	Search for active tumor foci
Ultrasound examination	Additional assessment of the pelvic organs and kidneys
Chest X-ray	Sometimes used to evaluate the lungs
Biopsy of a suspicious lesion	Confirmation of the nature of the find

Imaging answers the question "where is the disease located," while biopsy and histology answer the question "what is the disease?" Therefore, the correct diagnostic pathway combines both approaches. [54]

Biomarkers for treatment selection

Biomarkers are particularly important in advanced, recurrent, or metastatic cervical cancer. One key test is the measurement of programmed death ligand 1 protein in the tumor, as this marker may influence the appropriateness of pembrolizumab therapy in certain clinical situations. The US Food and Drug Administration has approved pembrolizumab in combination with chemotherapy, with or without bevacizumab, for persistent, recurrent, or metastatic cervical cancer if the tumor expresses programmed death ligand 1 protein with a combined positive score of 1 or higher on an approved test. [55]

For locally advanced cervical cancer, another important option has emerged: pembrolizumab plus chemoradiation. In January 2024, the US Food and Drug Administration approved pembrolizumab plus chemoradiation for patients with cervical cancer stages III-IVA according to the 2014 International Federation of Gynecology and Obstetrics classification. [56]

For some patients with advanced cancer, high microsatellite instability, a mismatch repair defect, and a high tumor mutational burden may be important. These markers are associated with the likelihood of response to certain immune-based therapies, particularly when standard treatment options have been exhausted or are limited. The American Cancer Society lists high microsatellite instability, a mismatch repair defect, a high tumor mutational burden, and positive programmed death ligand 1 as features that may suggest pembrolizumab may be used in certain situations of advanced cervical cancer. [57]

A targeted antibody-drug conjugate, tisotumab vedotin, is also available for recurrent or metastatic cervical cancer following chemotherapy. In April 2024, the US Food and Drug Administration granted conventional approval to tisotumab vedotin for recurrent or metastatic cervical cancer that progressed during or after chemotherapy. This drug is not a "test," but its availability demonstrates why modern oncology increasingly requires precise characterization of tumor type, prior treatment, and disease status. [58]

Sometimes, broader molecular profiling of the tumor is performed, especially if the disease is rare, aggressive, has relapsed after several lines of treatment, or the patient is being considered for a clinical trial. In such cases, the search is for rare targets that are not standard for all patients but may pave the way for personalized therapy. The National Comprehensive Cancer Network, in version 2.2026, emphasizes that current cervical cancer guidelines include systemic therapy and diagnostic testing as part of a unified clinical pathway. [59]

Biomarker or test	When it is especially important	How it can affect
Programmed death protein ligand 1	Recurrent, persistent, or metastatic cancer	Potential for pembrolizumab in certain regimens
High microsatellite instability	Common disease after treatment	The possibility of immunotherapy
Mismatch repair defect	Common disease after treatment	The possibility of immunotherapy
High tumor mutational load	Selected common tumors	The possibility of immunotherapy
Histological type	All confirmed cases	Choice of surgery, radiation therapy and drugs
Clinical staging	All invasive cases	Determines the basic treatment plan

Biomarkers are not needed equally by everyone at the initial screening stage. They are prescribed once the diagnosis has been confirmed and the results can significantly change treatment decisions. [60]

What is not a reliable test for cervical cancer?

There is no single blood test that reliably detects or rules out cervical cancer. Normal hemoglobin, normal white blood cells, normal biochemistry, and normal tumor markers do not preclude a biopsy if there are suspicious symptoms or visible changes. The Canadian Cancer Society classifies blood tests as supplementary tests that help evaluate health and treatment planning, rather than as primary confirmation of cancer. [61]

A positive HPV test should not be considered a cancer diagnosis. This test detects the presence of a high-risk virus, but most infections do not progress to cancer, especially if they are short-lived. The National Cancer Institute notes that HPV testing detects many infections that will not lead to dysplasia or cancer, especially in young women. [62]

A negative cytology result should not be considered an absolute guarantee if symptoms are present. Cytology samples cells from the surface and may miss a lesion located in the cervical canal, poorly sampled, or already present with a visible lesion requiring biopsy. The American Cancer Society emphasizes that screening tests are not diagnostic and cannot definitively confirm or rule out cancer. [63]

A home or self-collected HPV test should not be used as a substitute for a doctor's visit if bleeding, pain, or suspicious discharge is present. Self-collection is intended for routine screening of asymptomatic individuals at average risk, while symptomatic individuals require an examination, a sample from a physician, colposcopy, and a biopsy if indicated. The American Society for Colposcopy and Cervical Pathology specifically states that symptomatic patients, such as those with abnormal bleeding, are not candidates for self-collection in this situation. [64]

Erosion, inflammation, or discharge should not be treated with multiple courses of suppositories without confirming the cause if symptoms persist. Infections, benign changes, precancerous lesions, and cancer may overlap in complaints, so recurring spotting, contact bleeding, or a suspicious cervix require diagnostic evaluation. The US National Cancer Institute lists postcoital bleeding, vaginal bleeding, unusual discharge, and pelvic pain as possible manifestations of cervical cancer. [65]

Error	Why is it dangerous?	What is the correct way?
Donate blood only	Blood tests do not confirm or rule out cancer.	If there is a suspicion, tissue diagnostics is required.
Considering a virus equal to cancer	A positive viral test indicates risk, not a tumor.	Follow the algorithm for further examination
Reassure yourself with normal cytology for symptoms	It is possible to miss a focal process	Assess symptoms and perform an examination
Use self-collection in case of bleeding	This is no longer an average risk screening.	An in-person gynecological examination is required.
Treating discharge without examination	It is possible to delay the diagnosis	Exclude cervical pathology
Ignore bleeding after contact	This is a possible symptom of a serious pathology.	Perform an examination

Correct diagnosis of cervical cancer is not built around one “most accurate test,” but around a sequence: symptom or screening finding, in-person evaluation, colposcopy, biopsy, histology, staging, and biomarkers as indicated. [66]

Practical survey algorithm

If there are no complaints, age-related screening is the basis. In the United States, updated 2026 preventive guidelines recommend screening for average-risk women aged 21 to 65 years: from 21 to 29 years, a cytology test every 3 years, and from 30 to 65 years, primary testing for oncogenic types of human papillomavirus every 5 years or combined cytology and viral testing every 5 years is preferred; if a viral test is unavailable, cytology is continued every 3 years. [67]

If the HPV test is positive or the cytology is abnormal, the next step depends on the degree of risk. The physician considers the type of virus, the cytology result, previous screening history, age, and risk factors, and then chooses repeat testing, extended genotyping, double staining, colposcopy, or biopsy. The 2026 update of the US Federal Register specifically states that additional tests, including cytology, biopsy, colposcopy, extended genotyping, and double staining, may be necessary to complete the screening process. [68]

If symptoms are present, the algorithm changes: a gynecological examination and cervical assessment are required first. If the cervix appears suspicious, there is contact bleeding, unusual discharge, pain, or postmenopausal bleeding, the physician should not limit themselves to self-sampling or repeat screening in a few months. The American Cancer Society states that symptoms that may indicate cancer usually require a colposcopy and biopsy of the suspicious area. [69]

If the biopsy confirms invasive cancer, the patient is referred to a gynecologic oncologist. The stage, general condition, organ function, histology results, and treatment options are then assessed. The National Cancer Institute emphasizes that staging is performed after diagnosis because stage is an important factor in treatment selection. [70]

If the disease is widespread, recurrent, or metastatic, biomarkers are added to standard histology. This may primarily include programmed death ligand 1, as well as markers associated with microsatellite instability, genetic error repair, and tumor mutational load if the outcome could change therapy. [71]

Step	What is being done?	The main goal
1	Screening or symptom assessment	Understand if there is a risk
2	Examination and anamnesis	Find clinical signs
3	Virus test and cytology	Assess the risk of precancer and cancer
4	Colposcopy	See suspicious areas
5	Biopsy	Confirm the diagnosis with tissue
6	Histology	Specify the type and characteristics of the tumor
7	Visualization	Determine the stage
8	Biomarkers	Select drug treatment according to indications
9	Blood tests	Prepare for treatment and assess safety

This route helps avoid two extremes: panic in the event of a single positive viral test and dangerous reassurance in the event of symptoms against the background of normal or old screening. [72]

FAQ

Can cervical cancer be detected through blood tests? No, there is no universal blood test that reliably detects or rules out cervical cancer. Blood tests help assess anemia, organ function, and the safety of treatment, but a diagnosis is confirmed by a biopsy and histological examination of the tissue. [73]

What is the primary test for suspected cervical cancer? The primary confirmatory test is a biopsy of the suspected area followed by histology. Human papillomavirus testing and cytology help identify risk factors but are not a substitute for tissue confirmation. [74]

Does a positive HPV test mean cancer? No. It means a high-risk virus associated with precancer and cervical cancer has been detected, but in many people, the infection does not lead to cancer. Further management depends on the type of virus, cytology, age, and previous results. [75]

Does normal cytology rule out cancer? Not always. In the absence of symptoms, normal cytology reduces the risk, but if bleeding, pain, suspicious discharge, or visible changes in the cervix occur, the doctor may order a colposcopy and biopsy, regardless of whether the smear is old or normal. [76]

When is a colposcopy needed? A colposcopy is indicated after certain abnormal cytology results, a positive high-risk human papillomavirus test, a suspicious examination, or symptoms of cervical cancer. During a colposcopy, the doctor may take a biopsy. [77]

Why is endocervical curettage performed? It is performed to examine the cervical canal, especially if the transformation zone is poorly visible or if changes within the canal are suspected. The National Cancer Institute includes endocervical curettage in its list of diagnostic procedures for cervical cancer. [78]

Can self-testing for human papillomavirus (HPV) be used? Yes, in some countries and programs it is used for routine screening of asymptomatic people at average risk, but it is not suitable for abnormal bleeding, post-treatment surveillance for precancer or cancer, or for people with certain high-risk conditions. [79]

What tests are needed after cancer is confirmed? After a biopsy, histology, staging with imaging, a complete blood count, biochemical parameters, an assessment of kidney and liver function, and, in cases of widespread or recurrent disease, biomarkers that can influence the choice of systemic therapy are needed. [80]

What is programmed death ligand 1 (PDL) and why is it tested? It's a protein that helps tumor cells hide from the immune system. Its measurement may influence the use of pembrolizumab in persistent, recurrent, or metastatic cervical cancer. [81]

Should all patients have tumor markers? No. Squamous cell antigen and other markers may be useful in selected patients for prognosis or surveillance, but they are not suitable for initial screening and do not replace biopsy. [82]

Key points from experts

Dr. Nicholas Wenzensen, MD, PhD, MS, a senior investigator at the National Cancer Institute specializing in the molecular epidemiology and prevention of human papillomavirus-associated cancers, said: "A key area of modern diagnostics is moving beyond simple cytology to a more precise assessment of viral and cellular risk. The bottom line: HPV testing, genotyping, and biomarkers help better triage risk, but if cancer is suspected, a biopsy is the final word." [83]

Dr. Debbie Saslow, PhD, former managing director of the American Cancer Society's Human Papillomavirus and Gynecologic Cancers Division, said: "Refreshing approaches to screening are made possible by a better understanding of the role of HPV and the development of tests that can detect risk earlier. The bottom line: Viral testing is the cornerstone of prevention, but a positive result requires proper management, not panic." [84]

Dr. Nadim R. Abu-Rustum, MD, gynecologic oncologist at Memorial Sloan Kettering Cancer Center and chair of the National Comprehensive Cancer Network Panel on Cervical and Endometrial Cancer, said: Current guidelines integrate diagnosis, staging, surgical principles, and systemic therapy. The bottom line: Testing for cervical cancer is needed not only to confirm the diagnosis but also to develop a comprehensive treatment plan. [85]

American Cancer Society and American Society of Clinical Oncology, Medical Editorial Board: Cytology and human papillomavirus testing are screening tests, not definitive diagnostic tests. The practical lesson: If a suspicious result or symptoms occur, proceed to colposcopy and biopsy rather than repeating Pap tests indefinitely. [86]

The US Food and Drug Administration (FDA) has approved pembrolizumab for certain groups of patients with cervical cancer based on stage, clinical situation, and, in some regimens, programmed death ligand 1 expression as measured by an approved assay. The practical implication: in advanced or recurrent cancer, biomarkers are becoming more than just a formality, but rather a part of treatment choices. [87]