Human papillomavirus (HPV) is clinically classified into 2 categories: 1) high-risk and 2) low-risk types. Persistent high-risk HPV infection is a necessary but not sufficient condition for the development of cervical intraepithelial neoplasia and cervical cancer. Therefore, only a fraction of women with persistent high-risk HPV infection will develop severe cervical lesions or cervical cancer. Most HPV infections are transient and the risk of progression is minimal. Only a small proportion of infections are persistent, but persistent infection for more than 2 years strongly predicts a risk of cervical lesions, regardless of age factors. There are many types of HPV, and high-risk virus genotyping is probably the most important determinant of persistent HPV infection and progression of lesions in the cervix. HPV-16 has the strongest oncogenic potential and is associated with approximately 55-60% of all cervical cancer cases worldwide; HPV-18 is only second, with 10-15% of patients associated with it. The remaining cervical cancers are associated with approximately 12 additional HPV subtypes. It is not entirely clear what factors contribute to persistent HPV infection. Known cofactors that contribute to persistent HPV infection include smoking, immune system deficiency, and HIV infection. Most young women, especially those younger than 21 years, are able to clear HPV infection through an effective immune response within an average of 8 months, or 85-90% of women have reduced their viral load to a negative test within 8-24 months. In this population, most cervical lesions regress spontaneously as the infection clears. For women aged 30-65 years, the natural course of HPV infection does not change with age. For women aged 30 years and older, persistent infection after new HPV infection is unlikely. However, women older than 30 years of age are more likely to present with persistent infection. In perimenopausal or postmenopausal women, colposcopy with cervical canal scraping is recommended because of the decreased resistance to natural elimination of the virus and the tendency for the lesion to migrate internally into the cervical canal. The indications for HPV testing are: For women with cytologic ASCUS, the decision to perform colposcopy (triage) is made. For women aged 30-65 years or older, cervical cancer screening along with cytology (combined screening). HPV testing was approved by the FDA in 2014 for primary screening for cervical cancer in women 25 years of age and older. The test is used only for detection of high-risk HPV viruses. The time required for disease progression needs to be considered when assessing the appropriate screening interval. Most HPV-associated cervical lesions progress very slowly, and the exact time to progression from CIN 3 to cancer is not known, but the time to progression from CIN 3 to cancer at different ages of diagnostic screening is 10 years showing that precancerous status is a long process. Therefore, less frequent screening (at least one year interval) is appropriate for this slower disease process.