What is Atypical Squamous Cells of Undetermined Significance (ASC-US)?
Atypical squamous cells of undetermined significance, or ASC-US, is a term used to refer to unusual changes in the cells that line the cervix. This term, used in the Bethesda system for reporting cervical cell problems, describes changes that suggest a condition called squamous intraepithelial lesion. This condition isn’t as severe as a definitive diagnosis of this condition, but it still has varied degrees of severity. About 10% to 20% of patients with ASC-US have been found to show varying degrees of cervical intraepithelial neoplasia, which can be a precursor to a form of cervical cancer.
About ten years ago, cervical cancer was the third most common cancer in women globally. In some low-resource countries, it was the most common. We now know that a chronic infection with human papillomavirus (HPV) can lead to this cancer. This understanding has helped advance prevention methods which include HPV vaccination, regular cervical screenings, follow-up care, and treatment of precursor lesions.
In developed countries like the United States, the United Kingdom, and Canada, these preventative measures have significantly lowered both the occurrence and death rates from this cancer. But it’s important to know that a late diagnosis of invasive cervical cancer is usually fatal. These screenings are so important because early-stage cancer grows slowly and treatment is usually effective.
There’s a very high chance that screenings and treatments, especially in developing countries, can completely prevent deaths from cervical cancer. More recent research showed that globally, the rate of new cases of cervical cancer is about 13.1 (6.4 for North America) per 100,000 women per year. Cervical cancer is now the fourth most common cancer, following breast cancer, colorectal cancer, and lung cancer.
Although it has been suggested that there might be a genetic link to cervical cancer in some people who have a deficiency in a protein called alpha-1 antitrypsin, there’s no clear evidence of this yet. Instead, over 90% of cervical cancers are thought to be caused by high-risk types of HPV, particularly strains 16 and 18.
There are multiple ways to diagnose cervical cancer, including the Pap test, biopsies, liquid-based cytology, and tests for HPV DNA. And there are different risk factors associated with this condition. Women who have ever been sexually active are at risk, but some are at higher risk than others. This includes women who started having sex at a young age, have multiple sexual partners, are heavy smokers, have an HIV infection, or have a chronic HPV infection.
One way of screening for cervical cancer is to visually inspect the cervix, which provides immediate results. Negative results are reported as “negative for intraepithelial lesion or malignancy”. Cervical cytology, which is the study of cervical cells under a microscope, can detect several types of cell abnormalities, including ASC-US and different stages of squamous intraepithelial lesions, as well as invasive squamous cancer. It can also detect glandular cell abnormalities. Understanding ASC-US can help improve its management and treatment.
What Causes Atypical Squamous Cells of Undetermined Significance (ASC-US)?
Cervical cancer doesn’t come from a sexually transmitted infection, but it’s often linked to a persistent infection with HPV, a common sexually transmitted virus. There are over 200 types of human papillomavirus, and scientists have found 13 specific HPV strains that can lead to cancer. Among these, HPV 16 and HPV 18 are responsible for about 70% of all cases of cervical cancer, especially in women who also have HIV.
When it comes to cervical screening results, the atypical cells that are sometimes spotted are often associated with HPV infection and potential cancer development. However, these cells could also be present due to inflammation or other factors, not necessarily indicating cancer.
Research shows that about half of the women who have these atypical cells are infected with high-risk HPV. Yet, women with these cells but without the HPV infection are not at a higher risk of getting cervical cancer.
Studies have shown a high occurrence of high-risk HPV in patients with atypical cells. For instance, a study in Brazil found that 64% of such specimens carried high-risk HPV. Other studies have reported a high-risk HPV prevalence ranging from 11.2% to 81% in such patient groups. In a Turkish study, out of 129 women with abnormal Pap smears, 94 had these atypical cells, and nearly all of them were found to carry high-risk HPV.
Risk Factors and Frequency for Atypical Squamous Cells of Undetermined Significance (ASC-US)
Cervical precancer lesions are traditionally observed in women aged between 35 and 45, but are also common in HIV-positive women aged between 25 and 35. This slow-growing condition can become actual cancer typically after the age of 50. These lesions were formerly described by Papanicolaou as atypical pathology and categorized as ASC-US. This term is a mixture of normal, atypical, or suspicious/malignant cells at different stages, some with the potential to return to normal.
Today, these cells are classified using the cervical intraepithelial neoplasia or CIN grading system. CIN 1, CIN 2, and CIN 3 correspond to mild, moderate, and severe dysplasia respectively. However, the term dysplasia is no longer used. Instead, we use a system known as ‘the Bethesda system’, which categorizes these cells into ASC-US (atypical squamous cells of undetermined significance), and ASC-H (atypical squamous cells-high-grade cannot be excluded).
ASC-US is a common diagnosis and falls between a negative and a confirmed SIL. Further investigation of ASC-US can also reveal LSIL and HSIL cells. According to the Bethesda system, ASC-US/ASC-H is considered to be of lesser risk compared to LSIL (equivalent of CIN 1) and HSIL (CIN 2/3). The incidence of ASC-US varies and can be as low as 2.5%, as reported in a Japanese study, and as high as 19.1%, reported in another Japanese study.
Signs and Symptoms of Atypical Squamous Cells of Undetermined Significance (ASC-US)
ASC-US, which is found through a Pap test, is not something a woman would typically notice on her own as it often develops without symptoms. In those that do have symptoms, they can include a bloody, foul-smelling, or watery vaginal discharge, lower back pain, or signs of a urinary tract infection. The woman usually spots these symptoms during a general physical examination, where doctors check for signs related to conditions that may be causing the changes in the ASC-US.
Given that late-stage invasive cervical cancer doesn’t have a cure, it’s crucial to consider the risk factors that make a woman more likely to develop this type of cancer, so that proper preventative screenings can be arranged. Risk factors for cervical cancer include starting sexual activity at a young age, having multiple sexual partners, certain sexually transmitted infections like high-risk human papillomavirus (hrHPV) and HIV, and prolonged heavy smoking. There’s also an increased risk for women who have never had a Pap test, who may encounter a more aggressive precancerous lesion or full-blown cancer.
Here is a quick recap:
- ASC-US Symptoms: Bloody, foul-smelling, or watery vaginal discharge, lower back pain, or signs of a urinary tract infection
- Risk Factors for Cervical Cancer: Starting sexual activity at a young age, having multiple sexual partners, certain sexually transmitted infections like high-risk human papillomavirus (hrHPV) and HIV, prolonged heavy smoking, and never having had a Pap test
Testing for Atypical Squamous Cells of Undetermined Significance (ASC-US)
The American College of Obstetricians and Gynecologists (ACOG), American Cancer Society (ACS), U.S. Preventive Services Task Force (USPSTF) and the U.S. Food and Drug Administration (FDA) support regular cervical cancer screening for women age 21 to 65. Regular screening has been shown to decrease the incidence and death rates of invasive cervical cancer.
Women who are sexually active and present to outpatient departments with symptoms such as abnormal vaginal bleeding, discharge, painful urination or itching should be tested. Screening should be performed every three years for healthy, asymptomatic women between 21 and 29. Women between the ages of 30 and 65 should have additional tests every five years, due to the risks posed by the persistence of HPV, a virus that can lead to cervical cancer. This is in addition to the option of screening every 3 years.
Screening is not recommended for women under 21 as most HPV infections are transient or clear up completely. Women over 65 who have consistently tested negative can stop having screenings.
Triage testing is a combination of procedures including a Pap test or liquid-based cytology (LBC), visual inspection with acetic acid (VIA) and colposcopy, and HPV DNA testing. This is particularly useful for those diagnosed with ASC-US, a term used to describe abnormal cervical cells, as it helps to determine whether the result is normal, low-grade, or high-grade cell changes.
The examination process starts with a bimanual and speculum vaginal examination. This can be followed by a Pap test alone or in combination with the HPV DNA test. The HPV DNA test can also be done on its own. This test combination is recommended as it’s more sensitive than performing a cytological analysis alone.
Visual inspection with acetic acid (VIA) involves applying a diluted acetic acid solution to the opening of the cervix. The acid is absorbed by precancer cells, which then turn white, making them easier to see. After the acid application, the cervix can be examined with a handheld light or a colposcope. The result of the VIA exam is typically reported as negative, positive or suspicious for cancer. Biopsies are usually performed on patients with positive VIA results or those whose results are suspicious for cancer.
Treatment Options for Atypical Squamous Cells of Undetermined Significance (ASC-US)
Dealing with ASC-US, an unclear cell abnormality found in a Pap test, can be challenging because of its unpredictable progression. This condition could either resolve itself or escalate into more dangerous precancerous conditions, or even invasive cancer when not closely monitored. In some studies, almost 70% of ASC-US had returned to normal within 24 months, but about 7% had worsened into a higher grade of precancerous lesions.
ASC-US becomes a significant concern when it’s associated with a positive test for high-risk HPV, a virus known to cause cervical cancer. This correlation is because it’s unclear what portion of ASC-US may either regress to negative or progress to more severe conditions. Factors leading to its persistence are still not fully understood, however, high-risk HPV infection is known to linger longer in HIV positive patients, resulting in a higher occurrence of invasive cervical cancer.
An initial diagnosis of ASC-US might not need further treatment apart from a repeat Pap test or a visual inspection using acetic acid and possibly HPV genotyping, where possible. However, persistent ASC-US needs thorough analysis and treatment, especially if it continues to be a problem after 12 months.
In young patients with mild cell abnormalities and positive HPV tests, the guidelines recommend repeating the pap test after a year. If the results continue to show mild alterations or get back to normal, another repeat test is due after another year, and if it turns out negatively, regular age-based screening can be resumed.
The guidelines suggest using risk estimates when a patient turns 25 years old. Before the guidelines update, these patients had two management options. One was to conduct an HPV test, and if positive, colposcopy is needed, while negative results would mean a repeat pap test after three years. The second option was repeating the test after a year. If the results show abnormality, colposcopy is indicated. If results are negative, the patient can return to age-based screening.
Normal treatments include freezing or burning the abnormal cells, which is best for HSIL, a higher risk abnormal cells condition. Surgical interventions, like heating or freezing the abnormal cells, can lead to cell death with minimal or no side effects. These methods have been found to be a better option in resource-limited settings. Other than these, pharmacological methods have shown potential benefits in some trials.
For instance, one study reported a reversion to a negative Pap test in 63% of patients treated with a certain medication. However, other studies have indicated no positive impact on precancerous lesions. Hence, more research is required to understand the effects.
What else can Atypical Squamous Cells of Undetermined Significance (ASC-US) be?
The label “ASC-US” can stand for various health issues ranging from normal cell changes (NILM), low-grade or high-grade cervical intraepithelial neoplasia (LSIL/CIN 1 or HSIL/CIN 2+), to early stages of cervical cancer. However, it is considered ‘ASC-US’, the changes could also be as a result of inflammation of the cervix (cervicitis), air drying, bodily wear and tear due to age, and other routine changes. The conclusive way to identify what ‘ASC-US’ stands for in each case is through testing for human papillomavirus (HPV) DNA, using a colposcope (a device used to closely examine the cervix, vagina and vulva), and, if necessary, performing a biopsy, especially if ‘ASC-US’ keeps showing up in tests.
What to expect with Atypical Squamous Cells of Undetermined Significance (ASC-US)
Most cases of ASC-US, a term for unusual cells on the surface of the cervix, have a positive outlook when they’re accurately identified early. This is usually thanks to high-quality triage studies. If the HPV virus, often associated with ASC-US, is eliminated, the cervix can return to its normal state.
The progression to more serious conditions, HSIL/CIN 2+, can be managed with different treatments such as freezing the tissue (cryotherapy), removing the abnormal tissue using an electrically charged wire (LLETZ), or by a surgical procedure known as conization. With these treatments, patients have a real opportunity to completely reduce the risk of future development of cervical cancer in their lifetime.
Possible Complications When Diagnosed with Atypical Squamous Cells of Undetermined Significance (ASC-US)
ASC-US, which is an abnormal result from a Pap test, can present some problems if not properly managed or treated. This condition can actually resolve on its own, but if not followed up on properly, it might worsen and lead to more serious issues like HSIL/CIN 2+ or even invasive cancer. This tends to happen more in underserved populations who don’t have access to comprehensive screening services. In situations where resources or skilled staff are limited, an ASC-US diagnosis might be overtreated.
All forms of treatment carry some risk of complications, from minor pains during the procedure to other side effects like bleeding, postoperative pain, and brownish vaginal discharge. Other problems, such as severe and unpleasantly smelling vaginal discharge, can occur when cryotherapy or LLETZ are performed when there’s an ongoing infection like cervicitis, bacterial vaginosis, or vaginal trichomoniasis.
The recurrence of the lesion might suggest that the treatment hasn’t been up to par, due to incomplete removal of the lesion or the transformation zone, although the presence of HPV is a more potent sign of treatment failure. Cases of preterm birth have been reported in patients with CIN 2+ or AIS who have undergone conization, which is a surgery to remove precancerous cells from the cervix. The persistence of lesions is also typically more common in patients with HIV compared to those who are immunocompetent.
Potential Complications:
- Mild pain during the procedure
- Bleeding
- Postoperative pain
- Brownish vaginal discharge
- Severe and malodorous vaginal discharge
- Recurrence of lesions
- Preterm births for CIN 2+ or AIS patients undergoing conization
- Persistence of lesions in HIV-infected patients
Recovery from Atypical Squamous Cells of Undetermined Significance (ASC-US)
Patients who undergo cryotherapy and procedures like LLETZ/LEEP are typically treated as day patients and given common over-the-counter pain relievers like ibuprofen. They are generally advised to refrain from having sex for 4 to 6 weeks and to use condoms if they choose not to abstain. Additionally, they are told to avoid using tampons and vaginal douches. If patients experience a foul-smelling or persistent vaginal discharge after 14 days, they’re encouraged to return to their doctor for further evaluation and possible treatment.
If there are symptoms of an infection after the procedure, swab samples from the cervix or upper part of the vagina can be sent for lab analysis. In these cases, the patient may be given a treatment plan that includes doxycycline and metronidazole, to be taken orally, twice a day and three times a day respectively, for a week.
Preventing Atypical Squamous Cells of Undetermined Significance (ASC-US)
Cervical cancer, if it reaches an advanced stage, is lethal regardless of a woman’s HIV status. It’s crucial for all women to know about the importance of regular check-ups and the availability of the HPV vaccine. Even women with mild cervical abnormalities should be thoroughly educated and closely watched to ensure their condition doesn’t progress to invasive cervical cancer.
When considering the cost of cancer screening and treatment versus preventative measures, we should make prevention our priority; it’s the more affordable option. A combination of preventative practices and lifestyle changes can help lower the risk of cancer. This can include delaying sexual involvement, reducing the number of sexual partners, consistent and correct condom use, male circumcision, and quitting smoking. These steps can make a significant difference in reducing the risks of precancerous conditions and cancer.
