Cervical cancer was once the number one cause of death among women in the United States. With the advent of cervical smears and the widespread use of cervical cancer screening, cervical cancer-related mortality has declined significantly. With advances in understanding the evolution of cervical cancer and screening protocols, new screening guidelines are needed to determine the optimal screening protocol for cervical cancer to prevent invasive lesions while minimizing the potential negative effects of over-screening. Persistent infection with oncogenic human papillomavirus (HPV) can lead to the development of precancerous lesions and eventually invasive cancer. Despite the high incidence of HPV infection in sexually active individuals, only a minority of infected individuals progress to persistence. In 2011, the American Cancer Society (ASC), the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) updated their Common guidelines for cervical cancer screening were updated in 2011 by the ASC, ASCCP, and ASCP, and in 2012 by the U.S. Preventive Services Task Force (USPSTF). The optimal age for initiating screening is from age 21, regardless of the age of first intercourse. Although cervical cytology has been instrumental in significantly reducing the overall incidence of cervical cancer in the United States, the incidence of cervical cancer in women aged 15-19 years is extremely low, at about 0.15 cases per 100,000 per year, and has not changed much in the past 70 to 80 years. HPV infection and precancerous lesions in adolescent women are likely to be transient, so screening women before age 21 is likely to increase unnecessary colposcopies, but has little impact on cervical cancer prevention. In addition, treatment of this age group may lead to unnecessary anxiety and may adversely affect subsequent adherence to screening guidelines. Although cervical cancer screening is not recommended for women under 21 years of age, as a physician you should take the opportunity of your annual physical exam to emphasize reproductive health and related measures for future health benefits, such as HPV vaccine, reduction of risky sexual behavior, and recommendations for subsequent screening. Frequency of cervical cancer screening for women Current cervical cancer screening guidelines differentiate between women 21-29 years of age and women 30-65 years of age. women 21-24 years of age have a higher incidence of transient HPV infection, while women over 30 years of age have a higher incidence of persistent HPV infection and invasive lesions. However, it is important to note that annual screening is not recommended for any age group and by any method. Women 21-29 years of age should be screened every 3 years by liquid-based cytology or traditional scraping. If screening was performed before age 21, the results can be carried over to the 21-29 year period. Combined high-risk HPV screening is not recommended for this age group. Because of the high incidence of transient HPV infection in this age group, routine HPV testing is likely to result in unnecessary colposcopies, biopsies, or excisions that could adversely affect later reproductive tract health and fertility. Women aged 30-65 years should instead be screened every 5 years and should be screened with a combination of cytology and high-risk HPV. A review of multiple studies confirmed that combined HPV screening increases the detection of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer, thereby reducing the detection of these lesions at later screening. Several European studies have demonstrated a low detection rate of 0.28% for CIN3 or cervical cancer at 6 years if the combined screening result is negative. This result was supported in screening performed at Kaiser Permanente in northern California: a negative combined screening result was associated with a risk of developing CIN grade 3 or higher lesions of only 0.08% at 5 years. Of course, cytologic screening alone every 3 years is also acceptable. Another study compared the risk of developing cervical cancer at screening every 1, 2, and 3 years after a negative cervical cytology screening result. The authors concluded that cervical cytology screening every 3 years is also an acceptable screening regimen that strikes the right balance between benefits and adverse effects. Although increased HPV vaccination rates are expected to reduce the odds of persistent HPV infection, it is important to emphasize that vaccination must not interfere with current screening programs. Optimal time to stop screening Routine cervical cancer screening is not necessary for women 65 years of age and older who have had normal screening results within the last 10 years, a period of 10 years, or three consecutive negative cytology results, or two consecutive combined screening results. Older patients have narrower cervical migratory bands and are less susceptible to HPV infection. Persistent infection occurs in only a minority of patients after high-risk HPV exposure in women 65 years of age and older. In fact, even with persistent HPV infection, it takes years for cervical cancer to occur, so screening this population will only detect a small number of CIN2 or higher lesions, which has limited effect on cervical cancer prevention and reduction of cervical cancer mortality. Recommendations for screening in special populations Some women with high-risk factors have a higher risk of developing CIN3 or higher lesions, or even invasive lesions. An appropriate screening program needs to be developed separately for these patients. Women who have been previously treated for precancerous lesions should be followed up with cytology at 6 months and 1 year after treatment. If the cytology results are normal on both occasions after treatment, the screening program can be returned to the normal age group. However, such patients should be screened continuously until they reach 20 years of age, even if they are older than 65 years at the time of screening. Women who have undergone total hysterectomy do not need continuous screening as long as they have not been previously treated for CIN2 or higher grade lesions. Even if women in this group have a new sexual partner, routine cytologic screening or combined screening need not be recommended because they have a low risk of developing vaginal epithelial atypia and vaginal cancer. Patients with a previous history of CIN2 or higher grade lesions within 20 years who have undergone total hysterectomy should continue to be screened according to the guidelines. HPV-positive women should be screened cytologically every 6 months for the first year after diagnosis and annually thereafter. There is no solid evidence to support routine combined HPV screening, but high-risk HPV testing is recommended if the cytologic findings are atypical squamous epithelium of unknown significance.