Objective To investigate the natural changes of high-risk HPV (HR-HPV) in women with negative for intraepithelial lesion or malignancy (NILM) for regulating HR-HPV screening.Methods Four hundred and thirty-three newly-diagnosed women were enrolled from January 1st,2015 to December 31,2015 in Beijing Obstetrics and Gynecology Hospital.The ages of these patients were between 22 and 74 years,the average age was (45±21) years old.Two hundred and sixty-three cases were less than 50 years old,170 cases were more and equal to 50 years old.One hundred and fifty-six cases were HR-HPV positive,277 cases were HR-HPV negative.Follow up tests were conducted for all 433 patients,who were screened by ThinPrep cytologic test (TCT) combined with HR-HPV and were diagnosed with NILM,for a period of 1 year (at the 3,6,9 and 12 months intervals respectively),if the TCT results are abnormal and the HR-HPV test results are positive,will follow up colposcopy directed cervical biopsy.Results (1) HR-HPV natural changes:of 156 NILM cases with HR-HPV infection,42 cases (26.9％,42/156) turned negative within 3 months,88 cases (56.4％,88/156) turned negative within 6 months,99 cases (63.5％,99/156) turned negative within 9 months,and 100 cases (64.1％,100/156) turned negative within 12 months.The negative conversion ratio at 3,6,9 and 12 months for women at childbearing age (＜50 years) were significantly higher than those at non-childbearing age (≥50 years old;all P＜0.05).Of 277 NILM cases without HR-HPV infection,35 cases (12.6％,35/277) had new HR-HPV positive infections within 3 months,70 cases (25.3％,70/277) had new infections within 6 months,80 cases (28.9％,80/277) had new infections within 9 months,and 83 cases (30.0％,83/277) had new infections within 12 months.The new infections rate at 3,6,9 and 12 months for women at childbearing age (＜50 years old) were slightly higher than those at non-childbearing age (≥50 years old;all P＞0.05).(2) The progress of cervical leision:of 156 NILM cases with HR-HPV positive,no case progressed during 12 months follow-up.Of 277 NILM cases with HR-HPV negative,4 cases progressed to cervical intraepithelial neoplaisa (CIN) with HR-HPV infection and TCT abnormal during 12 months follow-up,including 2 cases pathology diagnosed with CIN Ⅰ,1 case with CIN Ⅱ,and 1 case with CIN Ⅲ.The progression rate was 1.4％ (4/277),which accounts for 4.8％ (4/83) of new HR-HPV infections cases in women.Conclusions The results of cytology combined with HR-HPV screenings suggest every 6 months for simple HR-HPV positive women,colposcopy directed cervical biopsy is recommended to assess cervical lesions if necessary.Cytology combined with HR-HPV screenings suggest every 12 months for simple HR-HPV negative women to early detection of cervical leision.