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Prof. Dr. Mustafa Özdoğan · Medical Oncologist

What Is an HPV Test, and Can It Replace the Pap Smear Test?

What Is an HPV Test, and Can It Replace the Pap Smear Test?
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Cervical cancer is the 4th most common cancer in women worldwide and also ranks fourth in cancer-related deaths. More common in low- and middle-income countries, it occurs less often in high-income countries. There are two reasons: strategies described by the World Health Organization include primary prevention and secondary prevention , two types of protection.

Primary prevention consists of efforts to protect against known cancer-causing microorganisms or carcinogenic substances, while secondary prevention focuses on early cancer diagnosis rather than its causes.

In developed countries, high rates of preventive vaccination (primary prevention), regular examinations and Pap smear and HPV DNA testing in women (secondary prevention) have reduced cervical cancer incidence.

- George Papanicolaou, who saved millions of women’s lives by discovering the Pap smear test

The place with the highest cervical cancer incidence in the world: Malawi

Malawi has the world’s highest cervical cancer rate. A study at Queen Elizabeth Central Hospital (QECH) in southern Malawi observed presentation, patient management and short-term outcomes in newly diagnosed patients.

Cervical cancer is the most common cancer in Malawian women, accounting for more than %40 of female cancers. The main cause of death and disease development is therefore HPV virus. The exact number of affected women is unknown because many cancers go unrecorded and Malawi lacks a national death reporting system. Two institutions, the Malawi Cancer Registry (MCR) and the International Agency for Research on Cancer (IARC) GLOBOCAN program, produced substantially different estimates. Incidence per 100.000 is 75,9, the highest cervical cancer rate worldwide. Mortality per 100.000 is 49,8, also the world’s highest. The 5-year survival rate is only %2.9. To illustrate how striking this is, in the United States cervical cancer 5-year survival across all stages shows a high success rate of %68.

In Malawi and similar regions, effective screening programs are hard to access and cancer awareness among the public and cancer workers is poor. Trained professionals, oncology staff, treatment facilities and equipment are also lacking. These factors mean cervical cancer is usually diagnosed at advanced stages. Alongside healthcare delays, “traditional healers” are another obstacle to accessing professionals.

- Cervical cancer symptoms and treatment (detailed)

Another factor reported to contribute to widespread cervical cancer is AIDS. Again using Malawi as an example, among adults (aged 15-64), 10.6 percent have HIV virus (men %12.8, women %8.2). Other important risk factors include human papillomavirus (HPV) infection, smoking and early age at first sexual intercourse.

As studies, causes and tests demonstrate, primary and secondary prevention are important in preventing cancer and cancer-related deaths. ASCO (American Society of Clinical Oncology) and WHO (World Health Organization) simultaneously recommended in 2014 the HPV vaccineas primary prevention for cervical cancer, including it in guidelines. The same guidelines recommended, regardless of country income, HPV testingas the main cancer screening test for secondary prevention. Its high cost, however, has limited use in low- and middle-income countries. Extensive research there showed that visual inspection with acetic acid (VIA) facilitates early-stage cervical cancer recognition and reduces deaths. ASCO consequently revised secondary prevention recommendations for these countries, stating that VIA could serve as the primary test when HPV testing is unavailable until healthcare infrastructure is strengthened.

- The story behind the discovery of the HPV vaccine

What is an HPV DNA test? What is a Pap smear test?

What is a Pap smear test?

The Pap smear test, discovered by Papanicolaou and named from the first letters of his name, remains one of the most widely used cancer screening methods. It can detect cervical cancer very early and even identify precancerous lesions before cancer develops. This inexpensive, easy method allows normal and abnormal smears from the vagina or cervix to be viewed microscopically and correctly classified. Since its introduction in the 1940s, the Pap smear has protected millions of women from cervical cancer’s adverse outcomes through early diagnosis or intervention before cancer develops. It is very simple: a smear is taken from the cervix with a soft brush or spatula, spread on a thin glass slide and examined microscopically. The Pap smear enables prevention and/or early diagnosis of cervical cancer.

What is an HPV DNA test?

HPV infection is the most important risk factor for cervical cancer. HPV DNA testing searches cervical cells for the virus’s DNA fragments, focusing on HPV types highly likely to cause cervical cancer (high-risk or precancerous types). It can be performed on a small tissue sample or smear from the affected area. A piece only millimeters in size from a skin or genital wart is sufficient. The test can also use a smear of normal tissue. HPV DNA material in the smear is investigated using methods such as polymerase chain reaction .

HPV DNA can also be analyzed in the smear collected for a Pap test.

In the figure below, the steps to follow according to possible HPV test results are explained.

how to interpret HPV DNA test primary screening program algorithm

- Meanings of abnormal smear test results

- What are conization and colposcopy, and how are they performed?

HPV testing may completely replace smear testing in the future

Gynecologic Oncology published two studies indicating that HPV DNA testing produces more accurate results than Pap smear testing. HPV testing appears superior. Because most cervical cancers are directly linked to this virus, demonstrating its DNA may provide better diagnostic guidance. HPV DNA testing may therefore be preferred where available. A recent Canadian study involving 19 thousand women showed that HPV testing detected cancer earlier and more clearly than Pap smears.

When and how often are early cervical cancer screening tests currently recommended?

The American Cancer Society recommends that every woman aged 20-30 undergo Pap smear testing every 3 years, and those aged 30-65 undergo co-testing (HPV DNA test + Pap smear) every 5 years to detect cervical cancer and precancerous lesions.

cervical cancer screening recommendation program

Because cellular changes occur very slowly, these intervals are generally sufficient. In most cases, a cell takes 10 years to change into cancer. A main reason for recommending HPV testing together with Pap smears is that instead of Pap testing every 3 years, co-testing every 5 years requires fewer tests, follow-up visits and treatments. Co-test is the name for having both tests together. Women with normal results have almost no likelihood of developing cervical cancer within 5 years.

HPV DNA testing is recommended in the following situations:

  • Being older than 30
  • An abnormal Pap smear result; a precancerous lesion called ASCUS, showing atypical squamous cells of undetermined significance

HPV, with nearly 200 subtypes, causes more than cervical cancer; it is also one of the main causes of head and neck cancers. However, HPV testing for early cancer diagnosis is currently recommended only for women. It is not routinely performed in other situations or in men; at a doctor’s or individual’s request, HPV DNA may be tested in warts, body fluids or tissue samples.

Sources

Gina Suzanne Ogilvie ve ark.
Effect of Screening With Primary Cervical HPV Testing vs Cytology Testing on High-grade Cervical Intraepithelial Neoplasia at 48 Months, The HPV FOCAL Randomized Clinical Trial.
Journal of the American Medical Association, July 2018
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