Prevalence And Genotype Distribution Of Human Papillomavirus In Women With Cervical Lesions In Guangxi, China

BackgroundIn spite of the evident decreasing of morbidity and mortality of cervical cancer under cervical lesion screening, cervical cancer is still the second most common malignant tumor after breast cancer for women in the world. It is widely believed that persistent infection with high-risk human papillomavirus (HPV) represents the prime risk factor in cervical carcinogenesis, which aroused highly attention about the prevalence of HPV in woman. Currently, mass screenings for HPV have been performed in many courtries and the data indicated that the distribution of HPV genotypes in various geographical areas and populations varies widely. Similar inadequate researches have been carried out in China, however the screening coverage remains imcomplete. The objective of the present study is to explore the prevalence of HPV infection and genotype distribution in patients with different cervical diseases in Guangxi, People's Republic of China.Materials and Methods1. A total of 304 cases of formalin-fixed, paraffin-embedded (FFPE), specimens were included in this study, which contains 29 cases of condylomata acuminate (CA), 34 cases of cervicitis, 28 cases of cervical intraepithelial neoplasia(CIN) ?, 25 cases of CINП, 25 cases of CINШ, 131 cases of squamous cell carcinoma(SCC) and 32 cases of adenocarcinoma (ADC).2. HPV DNA-chips technology which can explore 23 classes of common HPV subtypes at a time was employed to analyze the HPV infection and its genotypes distribution in 304 cases of FFPE specimens.3. Immunohistochemistry (IHC) was performed to test HPV protein expression in 123 cases of random samples (including 16 cases of cervicitis, 13 cases of CIN ?, 11 cases of CINП, 12 cases of CINШ, 27 cases of SCC, 15 cases of ADC and 29 cases of CA). The sensitivity between IHC and DNA chip technology was compared.4. DNA sequecing was carried out with 22 cases of HPV infective samples to investigate the specificity of HPV DNA chip technology.Results1.The relationship between HPV infection and cervical lesions from Guangxi regionA total of 241 HPV infective cases were detected by DNA chip technology among 304 cases of cervical lesion tissues, with an infective rate of 79.3%. HPV infective rates of each cervical disease group were: 27/29 (93.1%) in CA; 6/34 (17.6%) in cervicitis; 13/28 (46.4%) in CINⅠ; 16/25 (64.0%) in CINⅡ; 24/25 (96.0%) in CINⅢ; 129/131 (98.5%) in SCC and 26/32 (81.3%) in ADC. A significant rise of HPV infective rates can be found with more advanced cervical lesions (P< 0.05) except the CA group.2. HPV genotypes distribution in cervical lesions from Guangxi regionAmong a total of 23 kinds of HPV subtypes in DNA chip, there were 18 subtypes detected (including 14 high risk types and 4 low-risk types). The distribution of these types was as below: HPV16 was the most predominant type(136/304, 44.7%), followed by: high-risk types HPV18 (12.8%), HPV58 (5.9%), HPV52 (3.9%), HPV33 (3.6%) and low-risk types HPV11 (7.6%), HPV6 (3.9%), respectively.HPV distribution of different cervical lesions was analyzed. HPV low-risk types were the common infective types in CA, and HPV11 was the most common type (20/29, 69.0%), HPV6 was the second most common one (9/29, 31.0%), the positive rate of HPV52 was 6.9%(2/29); In the group of CIN, HPV16 was the predominant type(22/78), HPV58 was the second most common one (13/78), followed by HPV33 (2/29), HPV18(5/78), respectively; In SCC, HPV16 was the predominant type(103/131), HPV18 was the second (15/131), then HPV59(7/131), HPV58(4/131), HPV33(4/131), HPV31(4/131), respectively; In ADC, the predominant type was HPV18(19/32), the second was HPV16(7/32), and next HPV52(2/32).3. HPV single type infection, double type infections, multiple type infections in cervical lesions from Guangxi regionAmong a total of 241 HPV infective cases in this study, there were 200 cases of single type infection, 37 cases of double type infections, 3 cases of triple type infections and only one case of quadruple infections. HPV16, 18 were the most common high-risk double infections.There were 22 cases of HPV single type infection among all 27 HPV positive cases in CA, double infections accounted for 2/27, triple infections accounted for 2/27, and quadruple infections 1/27; In cervicitis, all HPV positive cases were single infection; In CINⅠ, single infection was 12/13, only one case was triple infections; In CINⅡ, single infection was 15/16, only one case was double infections; In CINⅢ, single infection was 17/24, double infections 7/24; In SCC, single infection was 106/129, double infections 23/129; In ADC, 22/26 were found as single infection, 4/26 were double infections. The type of multiple infections in CA was mainly low-risk multiple infections or co-infection with high-risk type and low-risk type, but in CIN or cervical cancer, high risk type multiple infections or co-infections with high-risk type and low-risk type were more common.4. Among 123 cases of random samples, a total of 62 HPV infective cases were detected by IHC, with a positive rate of 50.4%, whereas 95 cases were diagnosed as HPV infection via HPV DNA chip technology and the positive rate was 77.2%. The positive rate by HPV DNA chip technology was significantly higher than that by IHC(P<0.05).5. The sequences of 22 random samples were compared to the NCBI gene bank and the conformity was higher than 96%. The subtypes detected with sequencing was consistent with those from DNA chip technology.Conclusions1. Cervical lesions were closely related with HPV infection. High HPV prevalence was found in cervical lesions, nearly 100% in the group of SCC, and the HPV positive ratio raises with the cervical lesion grade;2. HPV16,18,58,52,33 were the five most common HPV types in cervical lesions from Guangxi. HPV16 was the predominant type, then HPV58 was the second common HPV type in group of CIN, however, HPV18 was the second common HPV type in the group of cervical cancer, and it was more relative with ADC;3. In cervical cancer or CIN, nearly all HPV infective types were high-risk types, but HPV low-risk types were closely related with CA;4. Most HPV positive cases were single infection, only one case was multiple infections (1/241) and three triple infective cases (3/241) and 43 cases were double infections (43/241). HPV low-risk type multiple infections was common in CA, however, the high-risk type multiple infections were more common in CIN or cervical cancer.5. DNA chip technology was an excellent HPV DNA detective method, due to its high sensitivity and specificity. And it can detect 23 HPV types at one time. It can be applied to HPV detection in FFPE specimens to support pathological diagnosis, clinical treatment and to predict the disease prognosis.