HPV is a large family with more than 130 subtypes distributed across multiple anatomical sites in the skin and mucosa, and more than 40 of the HPV subtypes in the implanted mucosa are associated with genital tract infections. HPV infection is present in almost all (>99.9%) lesions. Most oropharyngeal tumors (63%) and almost all anal cancers were also associated with persistent infection with high-risk HPV. The specific types of high-risk HPV remain controversial, with some suggesting as many as 15 or 16 species, 13 of which have been identified by the WHO as having the greatest oncogenic potential: 16, 18, 31, 33, 35, 39, 45, 51, 56, 58, 59, and 68. Of these, HPV 16 and HPV 18 cause 70% of cervical cancers, while HPV 45 and HPV 31 cause 5% and 10% of cervical cancers, respectively. Low-risk viruses are the pathogens that cause perianal warts of the genital tract and include HPV types 6, 11, 40, 42, 43, 44, 53, 54, 61 and 72. Of these, HPV 6 and HPV 11 are associated with 90% of genital tract warts and 96% of condyloma acuminatum. HPV is the most common type of sexually transmitted pathogen, with a worldwide prevalence of HPV infection of up to 10%. Infection rates are particularly high in young women (45% in women aged 20-24 years in the United States) and decline sharply after age 30. The lifetime risk of HPV infection is about 80%, and it is estimated that about half of all men and women have been infected with HPV once in their lifetime. HPV infection is transmitted through sexual intercourse. Compared to human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV-2), which are less transmissible pathogens, HPV is highly infectious. The transmission rate from men to women is as high as 0.4 to 0.8 per sexual encounter, and each male sexual partner has a 60% to 80% chance of transmitting HPV16 to women. Any factor related to sexual activity is a high risk factor for HPV infection in the genital tract, including younger age at the start of sexual life, number of sexual partners, recent changes in sexual partners, and sex with someone who has another sexual partner (both male and female). Postmenopausal women have infection rates of 14%-38%, and women over 65 years of age are more likely to have persistent HPV infection. Oral contraceptives and hormone supplementation therapy may upregulate HPV viral expression. Active and passive smoking are important factors in HPV infection, with ORs of 3.7 and 2.1, respectively, for developing cervical squamous carcinoma. There are three mainstream HPV testing strategies. All of these strategies have been tested in the United States and Europe. The first is cytology-based, with HPV for triage, and is used primarily in women under 30 years of age. This strategy is more appropriate for areas with high HPV prevalence. HPV testing is currently recommended for return testing for ASC-US (reflex HPV). The second type is HPV-based with cytology for triage. It is suitable for low HPV prevalence. The third is simultaneous testing for cytology and HPV and is currently used for women over 30 years of age. Cytology screening is the first-line cervical cancer screening protocol that reduces the incidence of cervical cancer and mortality. Retrospective studies from Japan and Sweden have confirmed that cytology screening significantly reduces the incidence of cervical cancer. However, the sensitivity of this regimen for detecting highly advanced lesions ranges from 55% to 94%. hpv was initially used for triage of abnormal cytologic findings and is now used for concurrent testing or as the preferred regimen. hpv testing increases the sensitivity of abnormal lesion detection, but has poor overall specificity. Four HPV testing protocols are approved in the United States and Europe: (1) HC2 analysis (Qiagen, Gaithersberg, MD, USA; formerly Digene Corp). (2) Cervista HPV HR (Hologic), which adds the HPV 66 test to HC2. Another Cervista test (Cervista 16/18) is also available for HPV 16/18 subtypes. (3) The Cobas 4800 system (Roche Molecular Sysytems, Alameda, CA USA) detects HPV 16/18 subtypes as well as a summary analysis of 12 other high-risk HPV species (HPV 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68). (4) Aptima mRNA (Gen-Probe, San Diego, CA USA), which detects E6 and E7 RNA, is able to screen for 14 high-risk HPV subtypes. The sensitivity is similar to HC2 (100%), but the specificity is higher (84%). One of the Cobas 4800 systems is the only method approved by the FDA in 2014 for HPV preferred screening. In well-screened populations, HPV testing and cytology are equivalent; however, in unscreened populations, HPV has a somewhat greater domain for detection of abnormal lesions. The risk of CIN3 in women with positive HPV 16 and normal cytology is 10%. Women with ASC-US who were positive for either HPV subtype had a 5-year cumulative risk of CIN3 and cancer of 6.8%. In cross-sectional studies, the sensitivity of high-risk HPV testing for precancerous lesions was superior to cytology, but this advantage was not present for invasive cancers. However, high-risk HPV testing has predictive value for future cervical cancer risk. The ideal time to repeat HPV after conization is 18-24 months. HPV testing can be used as a follow-up for the cure of cervical lesions because of its sensitivity of 85-97%. testing for HPV subtypes can help predict the risk of subsequent CIN3 recurrence. In 12,527 women in Sweden followed for up to 14 years, the cumulative incidence of CIN3 at 14 years was more than 28% in women positive for HPV 16, 18, 31, or 33, compared with 14-18% in women positive for HPV 35, 45, 52, or 58, and less than 10% in women positive for HPV 39, 51, 56, 59, 66, or 68. The time interval between cones (median 2.6 years) was shorter in women older than 40 years than in women younger than 40 years (6 years), and shorter in women with HPV 16/18 subtypes (1.8 years) than in other high-risk HPV subtypes (3.8-8.2 years). The poor specificity and positive predictive value of HPV limits its use as a preferred screening test, especially in younger women. In older women, who are more likely to have persistent HPV infection, HPV testing is of great clinical value. The risk of invasive cancer in women with ASC-H and HPV-negative is 2% in the subsequent 5 years. women with HSIL and HPV-negative have a 29% and 7% risk of CIN3 and invasive cancer, respectively, in the next 5 years. False negatives for HC2 in CIN2/3 ranged from 1-5%. False negatives were somewhat higher in women older than 40 years with smaller lesions. The detection rate of high-risk HPV varies with menstruation. Therefore single DNA tests are easily missed. Overall, HPV testing is too expensive for people in low-resource settings. There is also a careHPV (Qiagen, Gaithersberg, MD, USA) kit currently available for only $5, which appears to be superior to the vinegar white test, similar to cytology and HC2. The current accumulation of information on the incidence of cervical cancer over 65 years of age and the age at which cervical cancer screening is terminated needs to be reconsidered. Reducing the frequency of cytology and HPV testing may increase the windfall rate of cervical cancer. A predictive model found an additional 1 in 369 cases of invasive cancer if cytology and HPV testing were performed once every 5 years. A possible line of defense for future research: the incidence of invasive cancer in women over 65 years of age without hysterectomy? What factors contribute to persistent high-risk HPV infection and how can this persistence be assessed? What is the ideal follow-up protocol after high-risk HPV positivity? What are the screening guidelines for women after HPV vaccination?