Atypical Squamous Cells of Undetermined Significance

Abstract

Atypical squamous cells of undetermined significance (ASC-US) is a term used to report a category of cervical epithelial cell abnormalities described by the Bethesda system for reporting cervical cytology. It refers to abnormal cytologic changes that are suggestive of the squamous intraepithelial lesion (SIL) but are qualitatively and quantitatively less than those of a definitive SIL diagnosis. The clinical significance of ASC-US is based on the fact that this cytology finding is suggestive of a varying degree of SIL. Nearly 10% to 20% of patients with ASC-US prove to have a varying degree of cervical intraepithelial neoplasia (CIN), which are distinctive precursor lesions of cervical squamous cell carcinoma.About a decade ago, cervical cancer was the third most common cancer in women worldwide, and it was ranked as the first most common cancer in women in 42 low-resourced countries. However, the explained link between persistent infection with carcinogenic human papillomavirus (HPV) and the development of cervical cancer has paved the way for the advancement of primary and secondary prevention of this type of cancer. The currently used preventive measures include primary prevention by HPV vaccination and secondary prevention through cervical screening programs, patient's follow-up, and treatment of precursor lesions.In developed countries such as United States, United Kingdom, and Canada, widespread availability and access to cervical cancer screening have led to a significant reduction in both incidence and mortality from cervical cancer. In the United States, the incidence of cervical cancer cases has dropped to 7.4 per 100,000, while deaths from invasive cervical cancer have dropped to 2.8 per 100,000 women. A late diagnosis of invasive cervical cancer has a 100 percent mortality rate. The importance of screening in the prevention of cervical cancer is that precancerous stages are slow-growing and amenable to treatment. Active screening and treatment of women for precancerous lesions, particularly in developing countries, have a very high chance of total elimination of deaths from cervical cancer. A more recent study estimated the worldwide age-standardized incidence rate of cervical cancer to be 13·1 (6.4 for Northern America) per 100,000 women-years and an age-standardized mortality rate of 6·9 (1.9 for Northern America) per 100,000. In the same study, cervical cancer was ranked as the worldwide fourth most common cancer among women after breast cancer, colorectal cancer, and lung cancer.Though it has been previously theorized that alpha-1 antitrypsin deficiency may be a genetic predisposition, this is not yet confirmed. Rather, ample scientific evidence suggests that certain high-risk Human papillomaviruses (hrHPV) cause over 90% of cervical cancers, with 50 to 73.8% attributed to HPV 16 strain and 12 to 16.4 % attributed to HPV 18. The long-standing model of diagnosis has been by cytology using the Papanicolaou smear (Pap test) and biopsy, and most recently by liquid-based cytology (LBC). Other methods of diagnosis include HPV DNA test and colposcopy.Women that have ever been sexually active are at risk of developing cervical cancer; however, there are women with a greater risk profile than others. Risk factors commonly associated with the development of cervical cancer include younger age at sexual debut, multiple concurrent sexual partners, chronic intense smoking, HIV infection, and persistent infection with high-risk HPV. Though the Pap test dates back to the late 1940s, it has not been fully adopted and utilized in resource-limited settings for several reasons, including high cost and delay in getting results. Very low rates of Pap smear have been reported in resource-limited countries, including Jamaica at 15% and Nicaragua at 20% national coverage. In some Asian and African countries, Pap testing rates are even lower, or it does not even exist, compared to Jamaica. In other countries, at the time when cervical screening programs were not implemented, opportunistic Pap smear screening tests were used instead, but the rate was also remarkably low.Visual inspection of the ectocervix is the new way of screening, with immediate results and successful treatment of most of the identified precancerous lesions. Negative cervical cytology is reported as negative for intraepithelial lesion or malignancy (Negative/NILM). Squamous cell abnormalities that can be detected by cervical cytology include ASC-US, atypical squamous cells-high-grade cannot be excluded (ASC-H), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial session (HSIL), and invasive squamous cancer. Glandular cell abnormalities include atypical glandular cells (AGC), including endocervical and endometrial cells (not otherwise specified or favor neoplastic), endocervical adenocarcinoma in situ (AIS), and adenocarcinoma. This activity will improve the understanding of what ASC-US is and the implications and management of ASC-US diagnosis.