Cervical Dysplasia - How to Discern Pap Test Results

When it comes to women’s cervical health, the Pap test, also known as a Pap smear, is significantly important in reducing the incidence of cervical cancer.^[1] But with so many different stages of atypical or abnormal cells, even before the progression to cancer, it can be easily confusing for women to discern what their Pap results mean and what to do next to improve cervical health. A Pap test is used to sample the cells of the cervix.

The cervix is composed of squamous, or flattened, cells with a border of columnar cells. Because of the difference in shape and overall morphology of these cells, it is at this border that cells are most vulnerable to premalignant changes.^[2] By sampling cells from this area, we are able to examine them microscopically to look for abnormalities. You may have heard the words “ASCUS,” “LSIS,” or “CIN,” but what do these all mean? Should you be concerned? Only about 5–10% of all Pap test results in the United States come back as abnormal,^[1] but these abnormal results can leave women feeling anxious and worried.^[3]

Cervical Dysplasia and HPV

Cervical cancer is the second most common cancer in women aged 20–39 years old.^[4] It is almost always preceded by cervical dysplasia; therefore, in screening for cell abnormalities, we are looking to catch any form of cervical dysplasia early. This doesn’t mean that all cases of dysplasia will lead to cancer, but we are looking for evidence of any premalignant lesion or grouping of cells which can progress to cervical cancer. Once identified, dysplasia is typically 100% treatable in its noninvasive stages.^[2]

Almost all cases of cervical dysplasia are caused by a human papillomavirus (HPV) infection.^[2][4] HPV is a common sexually transmitted infection with virtually zero to few symptoms. It often clears on its own; however, some cases can progress, causing the development of cervical dysplasia. There are more than 120 different types of HPV, with 40 that affect the anogenital tract, and 15 strains that cause almost all cases of cervical dysplasia and cancer.^[3] Regardless of the strain that is causing issues, the course of treatment will typically not change. Therefore, HPV strain types aren’t specifically tested for in all cases of cervical dysplasia. That said, there are more aggressive subtypes, such as HPV 16 and 18, which can cause changes in as little as 18 months, but it can take about 10 years for the full progression from atypical cells to cervical cancer.^[2] It’s important to note that screening with a Pap test is still necessary for all women who have had an HPV vaccine. The original Gardasil vaccine protected against four strains: our more problematic HPV 16 and 18, but also strains 6 and 11. More recently, the “upgraded” vaccine, now called Gardasil 9, includes five additional strains. But regardless of immunization status, screening with routine Pap tests will still be required. The vaccines may help to reduce the risk of an infection, but they cannot prevent 100% of HPV cases.

Understanding Your Pap Test Results

There are varying degrees of cell abnormalities with regards to cervical dysplasia. We’ll start with the most benign of the bunch and work our way to the more worrisome.

You may have heard the term “ASCUS,” which stands for “atypical squamous cells of undetermined significance.” This indicates minor changes whereby cervical cells are not fully abnormal but are also not completely normal. This is one of the earliest indications that these cells are starting to change, or that the cervical tissue is attempting to repair itself. In this case, the Pap test should be repeated sooner than the recommended screening schedule, but regression to normal healthy cervical tissue is highly likely. In Canada, specifically Ontario, cervical screening guidelines have gone from once a year to once every three years. In cases of an abnormal test result, a second test is often conducted within about six months to monitor for changes. In addition to a second Pap smear, your ob-gyn may wish to perform a colposcopy. This is a small biopsy of a few millimetres of cervical tissue to be examined by a pathologist. Beyond simple atypia of cells is the development of mild cervical dysplasia. Also known as “low-grade squamous intraepithelial lesions” (LSIL), this represents our lowest grading of cervical intraepithelial neoplasia (CIN): CIN 1. Imagine your cervix as being composed of multiple layers of cells all squished down. LSIS or CIN 1 is diagnosed when we find that the basal cell layer—the most bottom layer of squamous cells—is thicker than it should be. It is here that we find early changes in the size, shape, and number of abnormal cervical cells. 

As cervical dysplasia progresses, the layers of cells that are affected extends out further to the surface of the cervix. A “high-grade squamous intraepithelial lesion” (HSIL) represents a moderate to severe form of dysplasia where 60–100% of the layers of cervical cells are affected. Also known as CIN 2 and CIN 3, this stage of dysplasia leads to a higher risk of further progression to cervical cancer.

Risk Factors

Although our current understanding is that cervical dysplasia is caused by an HPV infection, many carcinogens and other factors can contribute to the development of abnormal cervical cells. Remember that progression to cervical cancer is a very slow process, often taking 10–15 years in most untreated women. A warning sign of an abnormal Pap result is a great indicator to review your personal and sexual risk factors, and to make any lifestyle changes you can to promote tissue healing and prevention of further cell abnormalities.

Risk factors for the development and progression of cervical dysplasia include:

• Early age of first intercourse (younger than 18 years old). Biological changes in the cervix occurring in adolescence through puberty and into early adulthood cause a greater susceptibility to HPV infection and cervical dysplasia.^[1][2]
• Cigarette smoking.^[1][2]
• High number of lifetime sexual partners.^[5]
• Fear of having a Pap test and the stress associated with Pap findings.^[5]
• History of sexually transmitted infections, ^[5] and avoidance of condom use.^[2]
• Deficient dietary vitamin C (< 30 mg per day).^[2]
• Deficient dietary beta-carotene.^[2]
• Abnormal serum B₁₂ and folic-acid levels.^[6]

Prevention and Treatment

Reviewing our list of risk factors, there are many areas in which women and their partners can help prevent an HPV infection and subsequent dysplasia. Being mindful of sexual practices is a great first step. Eliminating risky sexual behaviour, including a reduction in the number of sexual partners, can help reduce the risk of developing cervical dysplasia. Additionally, ensuring proper condom use also decreases this risk. There is also a significant correlation between cigarette smoking and incidence of cervical dysplasia. This is no surprise, as cigarette smoke contains over 60 known carcinogens, which can lead to cancer development in multiple different organ systems and tissues throughout the entire body.^[7] But apart from reducing the factors that put us at risk, there are many things we can do to improve our cervical (and overall) health. For example, increasing consumption of vegetables and fruits containing antioxidants has been associated with lower risks of malignancies.^[2] One study in Brazil reported that an increased consumption of papayas was associated with a decreased risk of both LSIL and HSIL, and an increase in orange consumption decreased the risk of LSIL.^[4] Other major vitamins and antioxidants that are protective with regards to cervical cancer include a high intake of vitamin B12, vitamin C, vitamin E, beta-carotene, folate, and lycopene.^[8]

Folate/Folic Acid and Vitamin B12

Especially important in its 5 methyltetrahydrofolate (5 MTHF) form, folic acid is required for DNA synthesis and repair, as well as in methylation. Having low serum folate may increase risk of incorporation of HPV into the host genome.^[8] Associated with the cellular uptake of folic acid, vitamin B12 plays an important role in reducing homocysteine levels. Hyperhomocysteinemia (having too much homocysteine) increases the risk of cancer development because of the associated effects on DNA damage.^[6] One study reported that women with both adequate serum folate and vitamin B12 levels were 70% less likely to be diagnosed with HSIL.^[6] Therefore, the combination of folic acid and vitamin B12 may be significant in reducing DNA damage and thus the progression of cervical dysplasia.

Antioxidants

Vitamin C, vitamin E, beta-carotene, and lycopene are all potent antioxidants which prevent reactive oxygen species from causing oxidizing damaging to proteins and DNA within our cells.^[8] They are all considered to prevent neoplastic changes in the cervix, though doses need to be evaluated and should be recommended by a licensed health-care practitioner. Epigallocatechin gallate (EGCG) is a polyphenolic compound found in green tea and possessing many antioxidant, antimutagenic, and anti-inflammatory properties.^[9] Known to provide protection against various forms of cancer, EGCG has been shown to decrease the viability of cervical cancer cells.^[9] Although green-tea extracts are not recommended in pregnancy or during breast-feeding, nonpregnant women may wish to speak to their naturopathic doctor about including EGCG or daily matcha tea as a means of cervical protection or treatment for dysplasia.

Conclusions

Although many women tend to find Pap tests uncomfortable, this screening tool is vital for early detection of dysplasia and the prevention of cervical cancer. This is even true for women who have had the HPV vaccine, as the vaccine does not protect against all strains and all cases of HPV. In its noninvasive stages, dysplasia is treatable with a high likelihood of regression to normal healthy cervical cells. A healthy diet rich in vegetables and fruits high in antioxidant is a great way to help prevent abnormal cell changes. Supplemental antioxidants may also be used in the treatment of ASCUS and dysplasia, but should be done so under the supervision of a licenced health-care practitioner, and routine Pap tests should be continued to monitor for changes.