Human Papillomavirus Type-Specific Prevalence in Women with Cervical Intraepithelial Neoplasm in Western China

Abstract

Human papillomavirus (HPV) type-specific prevalence was studied in 600 cases of cervical intraepithelial neoplasm in western China by GenoArray test. HPV-16 and -58 were the most prevalent types, with prevalences of 37.8% and 21.8%, respectively. HPV-18 and -45 were uncommon types. The results show different type distributions from that of other regions, which is important evidence for the selection of future genotypes in HPV vaccines in western China.

TEXT

Cervical carcinoma is one of the most common malignancies that affect women worldwide. It is developed from a series of precancerous lesions called cervical intraepithelial neoplasm (CIN; graded from 1 to 3). Human papillomavirus (HPV) infection, the most important risk factor for cervical cancer development, can be detected in over 95% of carcinoma tissues (10). More than 100 different HPV genotypes are sequenced, of which about 15 types are called high-risk HPV because of their strong carcinogenic potentials (12). One important approach to prevent cervical cancer and CIN is the prevention of HPV infection by prophylactic vaccination. The currently available HPV vaccines are mainly against HPV-16 and -18 types, since they are the most important genotypes globally (7). However, HPV genotype prevalence varies in different countries or regions. In a previous study, we reported a high prevalence of HPV-16 and -58 in cervical carcinoma patients in western China, suggesting HPV genotype distribution may be quite different from other regions in the world (8). In the present study, we further investigated HPV type-specific prevalence in CIN lesions in a much larger patient population.

A total of 600 histologically diagnosed patients with CIN (CIN1, 143 cases; CIN2, 181 cases; and CIN3, 276 cases) were included. These patients visited West China Second Hospital, Sichuan University, one of the largest medical centers in western China, from January 2010 to March 2011. The histological diagnosis was verified by two independent pathologists who were blinded of the HPV status. Cast-off cells were scraped from cervical lesions by using plastic swabs and stored in physiological saline at 4°C until further use. Cervical samples were used for HPV DNA detection and genotyping by GenoArray test (Hybribio Limited, Hong Kong, China) as described previously (9). This kit can simultaneously identify 21 HPV genotypes, including 7 low-risk types (types 6, 11, 42, 43, 44, 53, and 81) and 14 high-risk genotypes (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68). Cochran-Armitage trend tests were used, and P values of <0.05 were considered significant. The attributable fraction of each genotype was estimated, and 95% confidential intervals (CI) were calculated as described before (6).

In the 600 CIN patients, the overall HPV infection rate was 80.8%, while that of the high-risk HPV type was 75.8%. As for the types, HPV-16 was the one most frequently found, with a prevalence of 37.8% and an attributable fraction of 34.2%. HPV-58 was the second most common genotype, which was detected in 21.8% of CIN patients and had an attributable fraction of 17.7%. Other common high-risk types include HPV-52, -33, and –31, with prevalences of 13.2%, 7.8%, and 5.7%, respectively. The attributable fractions of these types were 8.1%, 5.4%, and 3.0%, respectively. HPV-18, -68, -51, -39, -66, -59, -35, and -45 were uncommon high-risk types with attribution under 3%. Low-risk types, such as HPV-11, -53, -81, -6, and -42 were also detected in CIN patients; however, the prevalence was relatively low (Fig. 1).

Fig 1.

HPV genotype prevalence and attributable fraction in 600 cases of CIN patients in western China. The 95% confidential interval of each HPV attribution was calculated.

The overall HPV infection rates were 59.4%, 82.3%, and 90.9% for CIN1, CIN2, and CIN3, respectively (χ² = 7.53, P < 0.001), while high-risk HPV infection rates were 51%, 75.1%, and 89.1%, respectively (χ² = 8.54, P < 0.001). The result shows an association between grades of lesions and HPV infection, especially high-risk HPV infection. When type-specific HPV prevalence was analyzed, HPV-16 and HPV-58 were mostly related to the grade of CIN. HPV-16 infection rates were 16.1%, 30.4%, and 54.0% for CIN1, -2, and -3, respectively (χ² = 7.91, P < 0.001), while HPV-58 was detected in 14.0%, 21.5%, and 26.1% of CIN1, -2, and -3, respectively (χ² = 2.82, P < 0.003). HPV-33 prevalence was also related to the CIN grade (χ² = 2.93, P < 0.002). All the other high-risk genotypes or low-risk types exerted the similar increasing trend among the CIN lesions (Table 1).

Table 1.

HPV genotype distributions in women with different grades of cervical intraepithelial neoplasm (CIN)

HPV DNA or genotype	No. (%) of infections
	CIN1 (n = 143)		CIN2 (n = 181)		CIN3 (n = 276)
	Single and/or in concurrence with other HPV genotypes	Single infection	Single and/or in concurrence with other HPV genotypes	Single infection	Single and/or in concurrence with other HPV genotypes	Single genotype infection
HPV DNA	85 (59.4)		149 (82.3)		251 (90.9)
HR-HPV DNA	73 (51.0)		136 (75.1)		246 (89.1)
HPV-16	23 (16.1)b	11 (7.7)	55 (30.4)	35 (19.3)	149 (54.0)	107 (38.8)
HPV-58	20 (14.0)c	12 (8.4)	39 (21.5)	25 (13.8)	76 (26.1)	37 (13.4)
HPV-52	24 (16.8)	9 (6.3)	33 (18.2)	15 (8.3)	22 (8.0)	8 (2.9)
HPV-33	5 (3.5)d	3 (2.1)	11 (6.1)	6 (3.3)	31 (11.2)	16 (5.8)
HPV-18	4 (2.8)	2 (1.4)	11 (6.1)	4 (2.2)	12 (4.3)	3 (1.1)
HPV-68	5 (3.5)	2 (1.4)	3 (1.7)	1 (0.6)	3 (1.1)	0
HPV-53a	7 (4.9)	2 (1.4)	6 (3.3)	1 (0.6)	4 (1.4)	0
HPV-31	4 (2.8)	2 (1.4)	12 (6.6)	8 (4.45)	18 (6.5)	2 (0.7)
HPV-66	5 (3.5)	2 (1.4)	1 (0.6)	0	1 (0.4)	1 (0.4)
HPV-11a	5 (3.5)	3 (2.1)	11 (6.1)	7 (3.9)	5 (1.8)	2 (0.7)
HPV-42a	2 (1.4)	0	0	0	1 (0.4)	0
HPV-59	0	0	4 (2.2)	1 (0.6)	3 (1.1)	1 (0.4)
HPV-6a	5 (3.5)	3 (2.1)	4 (2.2)	1 (0.6)	2 (0.7)	2 (0.7)
HPV-51	2 (1.4)	1 (0.7)	0	0	1 (0.4)	0
HPV-35	1 (0.7)	0	1 (0.6)	0	1 (0.4)	0
HPV-39	2 (1.4)	0	5 (2.8)	0	1 (0.4)	0
HPV-45	0	0	0	0	3 (1.1)	2 (0.7)
HPV-81a	6 (4.2)	1 (0.7)	5 (2.8)	1 (0.6)	1 (0.4)	0

^aLow-risk types.

^bχ² = 7.91, P < 0.001, Cochran-Armitage trend test.

^cχ² = 2.82, P < 0.003, Cochran-Armitage trend test.

^dχ² = 2.93, P < 0.002, Cochran-Armitage trend test.

Globally, HPV-16 and -18 are the most oncogenic genotypes, which were associated with over 70% of invasive carcinoma, 50% of high-grade lesions (CIN2/3), and 35% of low-grade lesions (CIN1) (5, 11). HPV-45 is the third most common genotype, which is associated with 5% of the squamous cervical cancers, 2.5% of CIN2/3 lesions, and 5% of CIN1 (5, 11). HPV-58 was reported to be a rare genotype. However, to our knowledge, HPV-58 was detected more frequently in some areas of China, supporting diversified and geographic variations of HPV distribution (1–4). Our recent study found that HPV-58 was the second most prevalent genotype in cervical carcinoma in western China (8). In the present study, we further verified that in this area, HPV-58 is the second most prevalent genotype in CIN patients, which could be detected in over one-fifth of CIN lesions. In addition, 17.7% of CIN lesions were attributed to HPV-58 infections. HPV-16 is the most prevalent type, unsurprisingly. HPV-18 is less common, with the attribution under 3%. HPV-45, the third most commonly prevalent genotype in the worldwide scope, is extremely scarce in CIN patients in western China. Thus, in the area with high HPV-58 attribution, inclusion of HPV-58 should be considered in prioritization of HPV types in future vaccines (2).

In summary, our study demonstrates a high prevalence of HPV-16 and -58, but not HPV-18 and -45, in cervical precancerous lesions in western China, suggesting an important role of the two HPV genotypes in cervical cancer development in this area. What we have found may provide important evidence for the selection of future genotypes in HPV vaccines in western China.