Cervical Cancer Screenings: HPV, Pap Tests, And More

What is Cervical Cancer?

Yearly, over half a million women are diagnosed with cervical cancer, with over 300,000 deaths occurring on the international scale [1].The goal of cervical cancer screening is to detect and identify cells of the cervix which have undergone dysplasia. Dysplastic cells, or cells that have undergone dysplasia, may also be called “abnormal” or “precancerous” cells. In the past century, advancements in the understanding of cervical cancer have allowed for developments in the screening of precancerous conditions. Due to improvements in regular cervical cancer screening programs and Human papillomavirus (HPV) vaccinations, the rates of new cervical cancer cases and deaths have decreased since the 1980s [2]. Cervical cancer is now considered a preventable cancer. 

The Cervix

Cervical cancer is cancer of the cervix, the lower-most portion of the uterus. The cervix is anatomically divided into an upper endocervix and a lower ectocervix. The endocervix continues to the uterus, and the ectocervix opens into the vagina.

The transformation zone is located where the endo and ectocervix meet. Most cervical cancers form in the transformation zone, as cells within this region undergo continuous transformation and turnover [3]. This means that cells in the transformation zone gradually change, and if these changes are continually abnormal, they could turn into precancerous cells. 

Cells of the transformation zone can be sampled or biopsied to screen for precancerous conditions, as is done during the Papanicolaou test (Pap test) [4]. Healthcare providers use several terms to describe the cellular changes detected during cervical cancer screenings. These terms include cervical intraepithelial neoplasia (CIN), squamous intraepithelial lesion (SIL), and dysplasia. You might also hear these abnormal changes called pre-cancers or pre-cancer changes.

HPV and Cervical Cancer

Human papillomavirus (HPV) is a group of related viruses primarily transmitted through intimate skin-to-skin contact. There are over 200 strains of HPV, and almost 80% of sexually active individuals will be infected with a form of HPV at some point in their life [5]. Your immune system will fight off most HPV infections. If the infection clears, it becomes undetectable in 12–24 months. Many people will not experience symptoms and will not know they have it. In 10-20% of women, these infections remain persistent, and the infected cells can progress to precancer and cancer [6].

Human papillomavirus (HPV) is a group of related viruses primarily transmitted through intimate skin-to-skin contact. There are over 200 strains of HPV, and almost 80% of sexually active individuals will be infected with a form of HPV at some point in their life [5]. Your immune system will fight off most HPV infections. If the infection clears, it becomes undetectable in 12–24 months. Many people will not experience symptoms and will not know they have it. In 10-20% of women, these infections remain persistent, and the infected cells can progress to precancer and cancer [6].

HPV is the most common sexually transmitted infection (STI) in the world. You can contract the virus from sexual activities/intercourse with a partner who has HPV. HPV is transmitted through skin-to-skin contact and not transmitted via blood or body fluids, including semen [7]. To lower your risk of contracting the virus, use barrier protection methods, such as condoms or dams. Cells of the cervix, anus, penis, and throat are primarily targeted by HPV infections, specifically high-risk viral types HPV 16 and 18. Infection with HPV is the most common cause of changes to cervical cells [8].

HPV 16 & 18 are responsible for 70% of cervical cancer cases.

These other HPV types cause an additional 20% of cervical cancers [8].

HPV is recognized as the leading risk factor for precancerous changes; however, infection alone is not sufficient for cancer development. Additional cofactors are involved in cervical cancer development and progression, including immunodeficiency, oral contraceptive use, smoking, having a changed cervical microbiome, high parity/increased number of births and engaging in sexual activities at a young age and with multiple unprotected partners [9].

Early detection is ideal in any diagnosis. By detecting cervical cancer cells early, you can learn about treatment options available if cervical cell changes or abnormalities were to arise. HPV is preventable. Vaccination against HPV infection is available and works to protect you from developing HPV cancers.

The Pap Test

What is the Pap Test?

The Pap test, also called Pap Smear, is a gynecologic procedure used in cervical cancer screenings. Currently, it is the primary screening method. The procedure involves an exfoliative biopsy of the cervix to test for the presence of abnormal or precancerous cells.

What is the Pap test used for?

A Pap test is used to screen for cervical cancer and is done during a female pelvic exam.

Who should take the Pap test?

Cervical cancer screening is recommended for those with a cervix between the ages of 21 and 65. Healthcare providers typically recommend Pap testing every three years. There may be different guidelines based on your specific healthcare system.

If you have certain risk factors, your doctor may recommend more frequent Pap tests. Some of these include:

• A previous Pap test that detected precancerous cells or a diagnosis of cervical cancer
• A weakened immune system (due to infection, chemotherapy, radiation, recent organ transplant, chronic corticosteroid uses or other conditions)
• A history of smoking 

You and your healthcare provider can discuss the benefits and risks of Pap tests and decide when it’s time for you to begin cervical cancer screening and Pap testing. 

Pre-Procedure: How do I prepare for a Pap test?

The Pap test is a gynecologic procedure involving an exfoliative biopsy of cervix cells. During the procedure, cells of the cervix are sampled to be examined for abnormalities.

If you are menstruating at the time of your Pap test, you will likely be asked to reschedule. Your healthcare provider will likely instruct you to avoid intercourse and douching and recommend that you stop using vaginal products or medicines for two days before your test. These conditions could wash away or obscure abnormal cells, resulting in an inaccurate Pap test.

If you have any questions, please don't hesitate to ask your healthcare provider before going in for your procedure. Pap tests go more smoothly if you are comfortable, and your body is relaxed; it is important to be calm before and during your procedure.

Procedure: What happens during a Pap test?

When you arrive for a Pap test, you will be asked to change/undress and lie on your back on the examination table. Your knees will be bent, with your feet supported by stirrups. When you are comfortable, a healthcare provider will insert a speculum into your vagina. The speculum is a tool which increases visualization, allowing for the biopsy tool to be inserted to take a sample of cervical cells.

Procedure: Does a Pap test hurt?

Everyone’s experience is different. For some, the experience is mildly uncomfortable, while for others, speculum insertion can be painful or can lead to sensations of increased pelvic or vaginal pressure [10].

Next, the healthcare provider will insert an exfoliative biopsy tool into your vagina to take a sample of cells from your cervix. The tool (spatula, brush or, cytobrush, etc.) will vary depending on your specific hospital or clinic. During the biopsy, you will feel pressure at your cervix. The healthcare provider will remove the biopsy tool, and the sample of cells will be preserved and sent to a lab to test for potential abnormalities. Ask your healthcare provider what to expect following your Pap test and when to expect the results. 

Post-Procedure: What happens after a Pap test?

Following a Pap test, you might feel discomfort from the speculum insertion or biopsy. You might experience light vaginal bleeding following the test. Tell your healthcare provider if any discomfort, pain, or bleeding continues past 24 hours.

The results will inform your healthcare provider of abnormal cells identified from your Pap test or precancerous cellular conditions that may require further investigation. 

How do I interpret Pap test results?

Normal results

If only normal cervical cells were identified during your Pap test, you will receive a normal or “negative” result. You will not require further testing or treatment until you need to undergo another Pap test. 

Abnormal results

If abnormal cells were identified during your Pap test, you will receive an abnormal or “positive” result. A positive Pap test result is not a cervical cancer diagnosis. The positive result will depend on the cell types identified in your test [11]. If your Pap test is abnormal, your healthcare provider may suggest a colposcopy, a gynecologic procedure used to examine the tissues of the cervix, vagina, and vulva. From this point, if abnormal cells are visually confirmed, your healthcare provider may suggest a tissue sample biopsy. Cervical biopsy procedures provide further information on the abnormal cells and potentially precancerous conditions. 

Risks

There are potential risks associated with Pap tests [12]. The Pap test is a safe, reliable, and accessible method used in cervical cancer screening. Screening tests, including the Pap test, have a risk of providing misleading results.

Pap test results are examiner-dependent, meaning the results rely on the visual interpretation of cervical cells. The appearance of cervical cells can vary due to cellular changes that arise naturally throughout life (e.g., inflammation as associated with other infections, pregnancy history and atrophy or both).

It is possible to receive false-negative results. False-negative results mean that the test indicates no abnormality, even though you have abnormal cells. This can occur if the Pap test sample does not include sufficient tissue or cells or when blood or inflammatory cells obscure the abnormal cells. False-negative results can lead to undertreatment and leave individuals without important information about their health.

It is also possible to receive false-positive results. A false-positive result means that the results seem abnormal but are normal. A false-positive result may look like precancerous conditions,

but they are normal. False-positive results can result in overtreatment and can lead to unnecessary follow-up procedures and anxiety. Overtreatment is a cause for concern, as there are cases where lower-grade abnormalities will spontaneously regress without treatment [13].

Are there any alternatives to the Pap test?

Currently, the Pap test is the main available method for cervical cancer screening. The Pap test can be done in addition to an HPV test, which tests specifically for HPV-infected cells [14].

Recently, more digital resources have been developed, aimed at aiding in the screening and diagnosis of cervical cancer. For example, an artificial intelligence (AI) method recently developed uses two algorithms, a cervix locator algorithm and a feature extraction or classification algorithm, to identify abnormal cellular conditions and provide information about disease progression or regression [15]. While AI approaches hold promising early results, with increases in accuracy and reproducibility in compared to conventional screening methods, they still lack definitive measures of precancerous conditions. Further studies are needed with expanded sample sizes and follow-ups [16]. Please speak to your healthcare provider if you have questions about the Pap test or your options. 

What can I do to protect my cervical health?

Cervical cancer screening creates an early opportunity to identify abnormal cells or precancerous cellular conditions. Follow up with your healthcare provider, get treatment as needed, practice safe sex and advocate for your health. Be proactive and get screened regularly.

Vocabulary List (MW)

• Advocate: an individual who supports or argues for a cause.
• Biopsy: the removal and examination of tissue or cells from the body (aka sampled). 
• Cancer: an abnormal bodily state marked by abnormal cellular growth.
• Cervix: the narrow inferior portion of the uterus.
• Colposcopy: a gynecologic procedure which uses a colposcope (magnifying instrument) to inspect the vagina and cervix visually.
• Dysplasia: a cellular state or abnormal growth and development (aka abnormal or precancerous cells).
• False-negative: a test result that is incorrectly classified as negative.
• False-positive: a test result that is incorrectly classified as positive.
• Gynecologic procedure: a procedure involving the structures and organs of the female reproductive system.
• Human papillomavirus (HPV): a class of viruses which are transmitted through intimate skin-to-skin contact. HPV infection can result in the development of human papillomas (such as genital warts and plantar warts) and is associated with a risk of certain cancer development.
• HPV test: a test which involves the exfoliative biopsy of cervical cells and an assessment for high-risk types of HPV that are linked to cancer. HPV tests can be done independently or in conjunction with a Pap test.
• Lab: biopsy samples are sent to a pathology lab to be analyzed by a pathologist. The pathologist will analyze the cells or tissue from the sample and provide your healthcare professional with a report identifying cellular characteristics. 
• Menstruation: a cyclical discharging of blood, secretions, and tissue debris from the uterus that recurs in nonpregnant women at approximately monthly intervals. In the menstrual cycle, the menstruation phase occurs following the proliferative phase and before ovulation.
• Papanicolaou test (Pap test): a procedure used for the early detection of cervical cancer.
• Risk: the chance or likelihood that something will harm or otherwise affect your health.
• Risk Factor: a risk factor is something that increases the risk or susceptibility of developing a disease. It could be a behaviour, substance, or condition. Most cancers are the result of many risk factors.
• Screening: To test or examine for a condition or disease, often before there are symptoms.
• Speculum: a medical instrument that is inserted into the vagina to facilitate visual inspection or medication delivery.
• Stirrups: an attachment of the examination table designed to support the foot and legs during pelvic examinations and gynecologic procedures. 
• Transformation zone: a region of continuous cellular transformation and turnover. It is located where the endo and ectocervix meet. Most cervical cancers form in the transformation zone.
• Uterus: a muscular organ that is part of the female reproductive system and can grow and nourish the young during development before birth.
• Vagina: a part of the female reproductive system that leads from the cervix to the external orifice of the genital canal.
• Virus: microscopic agents that infect, grow and multiply using living host cells. Viruses can infect and impact humans, animals, and plants.