• Asia;
  • cervix;
  • human papillomavirus;
  • meta-analysis;
  • type distribution


  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

The aim of this study was to determine human papillomavirus (HPV) type distribution in women with and without cervical neoplasia from Asia and to estimate the potential future impact of an HPV 16/18 prophylactic vaccine in this region. A meta-analysis was conducted including 79 studies using polymerase chain reaction to detect HPV types. A total of 5954, 1653, 958, and 16,803 women with invasive cervical cancer (ICC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), and normal cytology or histology were included, respectively. Type-specific prevalence of HPV types 6, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 70, 73, and 82 were estimated and stratified by cervical lesion grade. Overall HPV prevalence was 85.9%, 81.0%, 72.9%, and 14.4%, respectively, in women with ICC, HSIL, LSIL, and normal cytology/histology. In ICC, HPV 16 was the predominant type (52.4%), followed by HPV 18, 58, 33, 52, 45, 31, and 35. The estimated HPV 16/18–positive fraction was 66.9%, 40.4%, 26.7%, and 3.3% in women with ICC, HSIL, LSIL, and normal cytology or histology, respectively. In ICC, the estimated HPV 16/18–positive fraction was about 70% in all Asian geographic regions, with the exception of Japan (51.3%). HPV 16/18 vaccines are estimated to provide about 67% protection against ICC in Asia. HPV 58 and 52 were among the five most common types in ICC in eastern and southeastern Asia but not in south central Asia. After HPV 16 and 18, the next most six common HPV types were 58, 33, 52, 45, 31, and 35 that accounted for additional 20% of cervical cancer cases in Asia. For optimal population coverage, these HPV carcinogenic types should be considered for second-generation HPV prophylactic vaccines.

Invasive cervical cancer (ICC) is the second most common cancer among women worldwide. According to estimates from the International Agency for Research on Cancer (GLOBOCAN 2002), an estimated 493,000 new cases and 274,000 deaths of cervical cancer occur among women worldwide each year(1). Approximately 265,885 (54%) cases occur in Asia(2), where cervical cancer remains a significant public health problem threatening women.

Human papillomavirus (HPV) has been established as a necessary cause of cervical cancer and its precursors, including cervical intraepithelial neoplasias grades 2 and 3 (CIN 2–3)(3–6). The utility of high-risk HPV DNA testing is being evaluated as a future cervical cancer screening methods(7). In contrast, HPV prophylactic vaccines hold great promise to reduce the global burden of cervical cancer(8). Thus, the detection and control of carcinogenic HPV types have become the focus of both primary and secondary cervical cancer prevention strategies(9). The determination of the most common HPV types in cervical cancer is instructive for the development of new HPV screening methods and HPV vaccines. Although previous publications of multicenter and meta-analyses provided total information about HPV type distribution in Asia(10–13), data from the Asian region have been limited in terms geographic coverage and cervical status.

HPV prophylactic vaccine has been successfully developed and will be available on the market of some Asian countries. To provide information for the public health and governmental decision makers and government, it is important to determine the detailed pattern of HPV type distribution and to estimate the potential protection of the current HPV 16/18 prophylactic vaccine candidates. The development of new second-generation HPV prophylactic vaccines will likely include additional priority carcinogenic types in addition to HPV types 16/18.

The purposes of this meta-analysis are to estimate the potential protection of an HPV 16/18 vaccine in different geographic regions of Asia and to determine the priority HPV types for the development of new HPV vaccines for the Asian region.

Materials and methods

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

Study selection

Source material was obtained from citations listed in Medline. References included in previous studies of Clifford on HPV type distribution in ICC(11), high-grade squamous intraepithelial lesions (HSIL)(12), and low-grade squamous intraepithelial lesions (LSIL)(13) in Asia were updated using the following key search terms: “cervical cancer/cervical neoplasms,”“human papillomavirus (HPV),”“human,”“female,” and “polymerase chain reaction (PCR)”. This analysis included peer-reviewed published literature in the Medline database up to October 2006 and was limited to studies fulfilling the following inclusion criteria: (1) the cervical specimen was from the Asian women, (2) clear description of pathology or cytology determined classification as follows: ICC, HSIL, LSIL, and normal cytology/histology, (3) sample sizes were more than 20 cases for each classification group. Studies at least included one category from four groups (ICC, HSIL, LSIL, and normal cytology/histology), (4) clearly described HPV DNA detection methods by PCR, (5) in addition to HPV 16, 18, 6, and 11, the detection of at least one additional HPV type, and (6) HPV type–specific prevalence stratified by cervical lesion grade (ICC, HSIL, LSIL, or normal). Where available, ICC was independently divided into squamous cell carcinoma (SCC) and adenocarcinoma and adenosquamous carcinoma (ADC). If histology-specific HPV prevalence was not reported or cases included other histology types, cases were classified as unspecific ICC. HSIL refers either to lesions cytologically equivalent to HSIL according to the Bethesda system or to lesions histologically confirmed as CIN 2–3. Cases of carcinoma in situ were included in the classification CIN 3. LSIL refers to lesions cytologically equivalent to LSIL according to the Bethesda system as well as to lesions histologically confirmed as CIN 1. For normal group, women were included with confirmed histology or cytology diagnosis from either population-based or hospital-based studies. Furthermore, if data or data subsets were published in more than one article, only the publication with the largest sample size was included.

Data abstraction

For each study, the following key information was extracted: (1) data of publication, (2) country or area of sample, (3) the classification of pathology or cytology (ICC [SCC/ADC], HSIL [CIN 3/CIN 2], LSIL [CIN 1], and normal), (4) type of cervical specimen (fresh or fixed biopsy tissue; exfoliated cell or combination), (5) the PCR primers used to detect HPV-positive samples, (6) diagnosis cervical outcome confirmed by: histology and cytology, and (7) type-specific and overall prevalence of HPV infection, which stratified by pathologic/cytologic classification. The countries were divided into four subregions in Asia according to geographic settings, sample size, and ethnicity includes: eastern Asia-1(14–38) (including China, Hong Kong, and Taiwan, where the majority are Chinese women), eastern Asia-2(39–71) (including Japan and Korea), southeastern Asia(72–79) (including Indonesia, Philippines, Malaysia, and Thailand), and south central Asia(3,80–90) (India and Iran). For studies comparing HPV prevalence across two countries, data were separated into regional components, respectively(21).

Estimation of type-specific prevalence

HPV prevalence data were expressed as proportion of the number of HPV-positive cases among all cases tested for HPV. Type-specific HPV prevalence was defined according to the specific publication and was presented for the most 18 common HPV types identified by the previous ICC meta-analysis(11), including HPV types 6, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 70, 73, and 82(11). Multiple HPV infections were separated into constituent types and thus type-specific prevalence included that in both single and multiple infections. Similarly, HPV type–specific prevalence was presented in descending order for individual HPV types in ICC for each histologic/cytologic classification, and only studies testing for a particular HPV type contribute to the analysis for that specific type. Therefore, sample size varied among the type-specific analyses.

Statistical analyses

For each histologic/cytologic classification of ICC, HSIL, LSIL, and normal cytology/histology, following sources of variation (publication year, geographic area, histologic determined type for ICC [only for ICC], diagnosis cervical outcome, type of specimen for HPV DNA testing, and type of PCR primers used) were introduced into a unconditional multiple logistic regression analysis. Final logistic models were conducted based on statistically significant variables. Overall adjusted HPV prevalence and 95% confidence intervals for stage of cervical lesion were estimated by adjustment for variables found to be significant in final model. P values comparing type-specific HPV prevalence were calculated using Chi-square tests.

Type-specific HPV prevalence was compared between HSIL /LSIL/normal, with ICC by prevalence ratios (PRs) with 95% confidence intervals. All statistical analyses were done in SAS version 8.0.


  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

Studies included

A total of 25,368 women from 79 studies(3,14–90) were included in analyses. Among them, a total of 5954, 1653, 958, and 16,803 women with ICC, HSIL, LSIL, and normal cytology/histology were included in 55, 27, 10, and 25 studies, respectively (Table 1). For ICC cases, the majority were SCC (n = 3231) in comparison with ADC (n = 533). Among women with normal cytology/histology, 12,670 women from population-based studies and 4133 women from hospital-based studies were included.

Table 1.  Overall HPV prevalence in 25,368 women from Asia, stratified by geographic region
Number of casesCrude/adjusted HPV %Number of casesCrude/adjusted HPV %Number of casesCrude/adjusted HPV %Number of casesCrude/adjusted HPV %Number of cases
  • a

    Includes 3231 SCC, 533 ADC, and 2190 unspecified ICC.

  • b

    Includes 12,670 and 4133 from population-based and hospital-based studies; among them, 2445 were based on cytology and 1688 were based on pathology.

  • c

    Includes China mainland, Hong Kong, and Taiwan (Chinese women).

  • d

    Includes Japan and Korea (Non-Chinese women).

  • e

    Includes India and Iran.

  • f

    Includes Indonesia, Philippines, Malaysia, and Thailand.

  • g

    Based on pathology cervical outcome/cytology diagnosis.

Eastern Asia-1c(14–38)269883.7/82.542668.3/75.15164.7/64.7169713.0/14.34872
Eastern Asia-2d(39–71)162383.4/86.697089.6/85.188074.5/74.612,26814.6/14.415,741
South central Asiae(72–79)49291.9/90.5198315.2/14.42475
Southeastern Asiaf(3,80–90)114192.2/91.125769.6/75.32733.3/33.385511.8/14.02280
Totalg(3,14–90)5954, 5905/4985.9/89.51653, 1227/42681.0/70.9958, 640/31872.9/41.3,16,803, 1688/15,11514.4/15.925,368

Overall HPV prevalence

The overall crude HPV prevalence was 85.9%, 81.0%, 72.9%, and 14.4% in ICC, HSIL, LSIL, and normal cytology/histology, respectively. Some geographic variation in overall HPV prevalence was noted among women with all cervical lesion grades. In ICC, overall adjusted HPV prevalence ranged from 82.5% to 91.1%, being lowest in China/Hong Kong/Taiwan (82.5%), higher in Japan/Korea (86.6%) and south central Asia (90.5%), and the highest in southeastern area (91.1%). In HSIL, overall adjusted HPV prevalence ranged from 75.1% in China/Hong Kong/Taiwan to 85.1% in Korea and Japan. For LSIL, HPV prevalence ranged from 33.3% in India to 74.6% in Korea and Japan. For women with normal cytology/histology, HPV prevalence had a smaller range of 14.0% in southeastern Asia to 14.4% in south central Asia.

In ICC, adjusted HPV prevalence was slightly lower in ADC (84.5%) than in SCC (86.1%), and this difference was not statistically significant. HPV DNA was significantly less frequently detected in biopsies tissue (83.4%) than either in cervical exfoliated cells (89.9%) or in both cells and biopsies (91.0%) (P < 0.0001). For PCR primers, the highest HPV prevalence was detected using short PCR fragment 10 (94.2%) and the lowest in specimens using type-specific PCR (82.8%). HPV prevalence increased with dates of study publication, from 82.8% in specimens included in publications before the year 2000 to 90.5% after the year 2004 (trend test P < 0.0001).

In normal women with cytology/histology, HPV prevalence was lower in the 12,670 women included from population-based studies (10.9%) than in the 4133 women included from hospital-based studies (25.0%) (P < 0.0001).

Summary of type-specific HPV prevalence

In decreasing order of HPV prevalence in ICC cases from Asia, the ten most common HPV types were 16, 18, 58, 33, 52, 45, 31, 35, 59, and 51 (Fig. 1). The HPV 16/18–positive fraction among women with ICC in Asia was 67% overall with geographic variation in subregion of Asia. After HPV 16 and 18, HPV types 58, 33, 52, 45, 31, and 35 accounted for additional 20% of ICC cases in this region. The proportion of ICC cases attributed to HPV 16/18 appeared to differ somewhat by geographic region, being the highest in south central Asia (77.6%), in the order of southeastern Asia (72.0%), Korea (70.3%), China/Hong Kong/Taiwan (69.5%), and being the lowest in Japan (50.3%) (P < 0.0001).


Figure 1. Percentages of 5954 ICC cases attributed to the most common HPV types in Asian region.

Download figure to PowerPoint

In ICC, HPV 16 type–specific prevalence in SCC was 53.8%, significantly higher than that in ADC (32.3%) (P < 0.0001). Similar results were found for the HPV 16 phylogenetically related types 58, 52, and 35 (P < 0.05) but not for HPV 33 and 31. In contract, the HPV 18 was statistically more common in ADC (34.4%) than SCC (11.1%) (P < 0.0001) (Fig. 2).


Figure 2. The HPV type distribution in 25,368 women from Asia, stratified by grade of cervical lesion .

Download figure to PowerPoint

Among all ICC cases, there appeared to be some variation in the prevalence of the third, forth, and fifth most common HPV types after HPV 16 and 18 in different subregions of Asia. HPV 16 and 18 were followed by HPV 58, 52, and 33 in eastern Asia (including China/Hong Kong/Taiwan and Korea and Japan), by HPV 45, 52, and 58 in southeastern Asia, but HPV 45, 33, and 35 in south central Asia (Fig. 3). Overall, HPV 58 and 52 were among the five most common HPV types in ICC in all regions of Asia except in south central Asia (India and Iran).


Figure 3. The type distribution of the eight most common HPV types by geographic region in 5954 women with ICC from Asia.

Download figure to PowerPoint

A similar sequence pattern of HPV type–specific prevalence was found in women with HSIL, LSIL, and normal cytology/histology. The ten most common HPV types were 16, 58, 52, 18, 33, 51, 31, 56, 35, and 45 in HSIL;16, 58, 52, 18, 51, 56, 39, 31, 68, and 35 in LSIL; and 16, 52, 58, 51, 18, 56, 35, 33, 39, and 31 in normal histology/cytology, respectively. For HSIL, LSIL, and normal group, HPV 16/18–positive fractions were 40.4%, 26.7%, and 3.3%, respectively.

The PRs are presented in Table 2 for comparisons of ICC to HSIL cases (ICC/HSIL) and ICC to LSIL cases (ICC/LSIL). PRs for HPV types 16, 18, and 45 were 1.6, 2.0, and 1.6 for ICC/HSIL comparisons and 2.6, 2.2, and 2.2 for ICC/LSIL comparisons, respectively. PRs for all other HPV types were less than 1 for ICC/HSIL, although HPV 33 also showed a PR notably higher than 1 for ICC/LSIL comparisons.

Table 2.  HPV type–specific prevalence and PRs in women from 25,368 Asia, stratified by grade of cervical lesion
Number of case (%)Number of case (%)Number of case (%)Number of case (%)ICC/HSIL PRNumber of case (%)ICC/LSIL PRNumber of case (%)
  • a

    Type-specific prevalence higher in SCC than in ADC.

  • b

    Type-specific prevalence higher in ADC than in SCC.

HPV 16a5954 (52.4)3231 (53.8)533 (32.3)1653 (33.1)1.6958 (20.0)2.616,803 (2.6)
HPV 18b5853 (14.5)3139 (11.1)524 (34.4)1587 (7.3)2.0790 (6.7)2.215,048 (0.7)
HPV 58a4922 (5.5)2708 (5.5)473 (1.3)1275 (11.8)0.5931 (7.9)0.716,470 (0.9)
HPV 335823 (3.8)3187 (3.7)527 (2.7)1162 (6.6)0.6590 (1.2)3.215,194 (0.5)
HPV 52a4585 (3.8)2556 (4.2)467 (1.9)1066 (10.6)0.4731 (7.3)0.512,320 (1.5)
HPV 453857 (2.8)2297 (2.8)302 (3.3)585 (1.7)1.6387 (1.3)2.210,204 (0.3)
HPV 314774 (2.3)2623 (2.2)332 (0.6)941 (5.2)0.4563 (3.4)0.715,048 (0.4)
HPV 35a4307 (1.3)2602 (1.5)310 (0)835 (3.1)0.4677 (2.5)0.514,731 (0.6)
HPV 593880 (1.2)2297 (1)238 (2.1)640 (1.4)0.9563 (0.9)1.310,481 (0.3)
HPV 513712 (0.7)2256 (0.9)238 (0)737 (5.7)0.1931 (5.7)0.112,090 (0.9)
HPV 563974 (0.6)2256 (0.7)373 (0.5)640 (3.4)0.2563 (5.3)0.110,481 (0.7)
HPV 684049 (0.6)2300 (0.4)379 (1.3)640 (0.8)0.8563 (3)0.210,481 (0.3)
HPV 64907 (0.4)2850 (0.4)387 (0)714 (0.6)0.7483 (0.8)0.510,307 (0.2)
HPV 822180 (0.4)1341 (0.1)106 (0)162 (0.6)0.751 (0)8182 (0.1)
HPV 393766 (0.3)2256 (0.3)238 (0)568 (1.4)0.2477 (3.8)0.110,351 (0.4)
HPV 663597 (0.2)2256 (0.4)238 (0)412 (1)0.2405 (2.2)0.110,044 (0.3)
HPV 703344 (0.2)2189 (0.2)225 (0)282 (0.4)0.5231 (1.7)0.19221 (0.3)
HPV 732982 (0.2)2172 (0.2)200 (0)246 (0)196 (0.5)0.49177 (0)


  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

Overall HPV prevalence

This meta-analysis presents data on HPV type–specific prevalence in over 25,368 women in Asia. Overall HPV prevalence in 5954 ICC cases (85.9%) was lower than the almost 100% prevalence detected using most sensitive PCR HPV detection methods(4). This lower HPV prevalence may be due to the inclusion of studies using PCR detection techniques of lower sensitivity or ascertaining a relatively smaller number of HPV types. Of the 5954 ICC cases included, 76% cases were from eastern Asia, with slightly lower HPV prevalence of 83–86%. A quarter (24%) of ICC cases came from south central and southeastern Asia, with a higher HPV prevalence of 90–91%. The more proportional cases from eastern Asia degraded the average overall HPV prevalence. Adjusted HPV prevalence found in SCC and in ADC cases from Asia were not different statistically, confirming previous conclusions that HPV infection is the primary causal agent for both SCC and ADC consistently worldwide(6,91).

This analysis includes data from 1653 HSIL and 958 LSIL cases, notably increasing the number of cervical neoplasia cases included in previous reviews. With the inclusion of these new cases, overall HPV prevalence of HSIL (80.8%) and LSIL (72.8%) in Asian women were similar to that previously reported (84.2% and 67.1%, respectively)(12,13). In 16,803 women with normal histology/cytology, overall HPV prevalence appeared to be similar within all of the subregions of Asia (eastern, south central, and southeastern) and was slightly higher (∼14%) than that found in 6100 Asian women with normal cytology (8.2%) in population-based samples using General Primer 5, +/6+ HPV DNA detection assays(92). The 12,670 normal women were from population-based study (10.9%), which was similar to that in previous study(92), and 4133 women were from hospital-based study (25.0%). The histologic normal group possibly included the case with abnormal cytology that could heighten the overall HPV prevalence in normal group of Asia.

The overall adjusted HPV prevalence was similar between four geographic subregions within Asia for women with ICC, HSIL, and normal cytology/histology in our study. However, HPV prevalence appeared to differ among LSIL cases within geographic regions of Asia. The possible reason was that the overall sample sizes for LSIL were limited in stratified analyses by geographic region, with one study from Thailand showing a notably low HPV prevalence (33.3%, n = 20)(80). Additional studies with a larger number of women are required to reliably estimate HPV type distribution in LSIL from Asia.

HPV type–specific prevalence

HPV 16 was clearly the predominant type in Asian women with and without cervical neoplasia. In ICC, the attributable fraction of HPV 16 was 52.4%, slightly higher than the figure of 45.9% in 3091 women with ICC from Asia in Clifford’s previous systematic review(11). HPV 16 was more common than HPV 18 in SCC cases, and HPV 18 was the most common type in ADC, consistent with results of previous studies(11,93).

The potential impact of an HPV 16/18 prophylactic vaccine for the future prevention of cervical neoplasia can be estimated from the HPV 16/18–positive fraction in women with cervical neoplasia, under the assumption of wide vaccination coverage. Our data suggest that an HPV 16/18 prophylactic vaccine has the potential to prevent an estimated 67% of ICC cases in Asia. The HPV 16/18–positive fraction was about 70% of ICC cases in all Asia but not in Japan (50.3%). One interesting finding was that the proportion of ICC cases attributable to HPV types 16 and 18 appeared to be slightly lower in Japan (∼50%). This lower fraction of HPV 16/18 cases in Japan may be due to a potential lower detection of HPV 16 and/or 18 by the “L1C1/C2” PCR primer, which is widely used in Japan(41,50,62), and it need furthermore investigation.

After HPV 16 and 18, HPV types 58, 33, 52, 31, 33 35, and 45 were the most six common HPV types in ICC. Figure 1 showed the possible cumulative protection fraction of vaccine with the priority HPV types, according to the descending order of HPV type–specific prevalence in ICC. Our analysis indicated that the prevention of HPV 16, 18, 58, 33, and 52 could potentially provide ∼80% protection of ICC. The prevention of HPV types 16, 18, 58, 33, 52, 31, 35, and 45 could potential provide ∼87% protection of ICC cases in the Asian area, which was similar to other geographic regions(10,11,93). Figure 3 showed that HPV types 58 and 52 were among the five most common types in ICC in all geographic regions of Asia, except south central Asia (India and Iran), confirming results of previous reviews(11,13,37,38,93).

The PR values of HPV 16, 18, and 45 in ICC/HSIL and ICC/LSIL were greater than 1, indicating that HPV 16, 18, and 45 are more likely to progress to cervical cancer from LSIL and HSIL than the other HPV types, supporting results from previous similar study(13,94,95). Although HPV 33 also appeared to have a higher progression potential from LSIL to ICC based on these PR data, further data are needed with larger samples sizes to confirm findings.

The HPV 16/18–positive fractions were 41.3% in HSIL, 26.8% in LSIL, and 3.3% in normal histology/cytology, and ranged 36–50%, 11–33%, and 0.9–8%, respectively. The findings are largely consistent with those from a previous review including fewer cervical neoplasia cases, which showed that the fractions were about 41% in HSIL and 32% in LSIL, ranging from 41% to 67% and from 16% to 32% in HSIL and LSIL, respectively(93).

Our findings provide a detailed description of overall and type-specific HPV prevalence in Asia, stratified by geographic region. With a large sample size and systematic review of the literature, these findings notably improve our understanding of HPV infection prevalence in women having different grades of cervical neoplasia in Asia. Our review, however, was limited as some studies used relatively insensitive assays or only detected a subset of HPV types. Thus, we expect that our estimated figures on the proportion of HPV 16- or HPV 18-positive ICC cases would have been higher if most sensitive PCR assays had been systematically used in all included studies, and if HPV-negative ICC cases have been typed using more sensitive assays(10).

Among 265,885 new cases of cervical cancer occurring in the Asian region, the contributions of eastern Asia, southeastern Asia, and south central Asia were 61,132 (23%), 42,538 (16%), and 157,759 (60%), respectively(2). Although approximately 50% new cases of Asia occur in India and 3% are estimated to occur in Japan(2), the proportion of cases with HPV-typing data from India was notably low (4%), in comparison to Japan, which accounted for 30% of included cases. The inclusion of a relatively greater number of ICC cases typed from Japan may have slightly reduced the proportion of HPV 16– and/or HPV 18–positive ICC cases in Asia. Moreover, the cases were not obtained from every Asian subregion, as some countries had no published HPV DNA–typing data (eg, Myanmar, Singapore, and Vietnam) and were thus not included in this systematic review.

In summary, the estimated HPV 16/18–positive fraction was 66.9% for ICC, 40.4% for HSIL, 26.7% for LSIL, and 3.3% for women with normal cytology/histology from Asia. Thus, first-generation HPV 16/18 vaccines have the potential to provide ∼67% protection against ICC in Asia. HPV 58 and 52 were among the five most common types in ICC in all Asia but not in south central Asia. After HPV 16 and 18, HPV types 58, 33, 52, 45, 31, and 35 accounted for additional about 20% cervical cancer of Asia and should be considered for inclusion in second-generation HPV vaccines.


  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

We are grateful to all of authors who made detailed data available from their published studies, and we express our gratitude to GlaxoSmithKline for its technical support during the identification of published studies for this work.


  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References
  • 1
    Parkin DM, Bray F, Ferlay J et al. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74108.
  • 2
    Ferlay J, Bray F, Pisani P et al. GLOBOCAN 2002: Cancer incidence, mortality and prevalence worldwide. IARC Cancer Base No. 5, version 2.0, Lyon: IARC Press, 2004. Available at: [accessed Nov 25, 2006].
  • 3
    Bosch FX, Manos MM, Munoz N et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst 1995;87:796802.
  • 4
    Walboomers JMM, Jacobs MV, Manos MM et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:129.
  • 5
    Munoz N, Bosch FX, De Sanjos S et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003;384:51827.
  • 6
    Castellsague X, Diaz M, De Sanjose S et al. Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention. J Natl Cancer Inst 2006;98:30315.
  • 7
    Franco EL. Chapter 13: Primary screening of cervical cancer with human papillomavirus tests. J Natl Cancer Inst Monogr 2003;31:8996.
  • 8
    Harper DM, Franco EL, Wheeler C et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004;364:175765.
  • 9
    Schiffman M, Castle PE. The promise of global cervical-cancer prevention. N Engl J Med 2005;353:21014.
  • 10
    Munoz N, Bosch FX, Castellsague X et al. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int J Cancer 2004;111:27885.
  • 11
    Clifford GM, Smith JS, Plummer M et al. Human papillomavirus types in invasive cervical cancer worldwide: a meta-analysis. Br J Cancer 2003;88:6373.
  • 12
    Clifford GM, Smith JS, Aguado T et al. Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis. Br J Cancer 2003;89:1015.
  • 13
    Clifford GM, Rana RK, Franceschi S et al. Human papillomavirus genotype distribution in low-grade cervical lesions: comparison by geographic region and with cervical cancer. Cancer Epidemiol Biomarkers Prev 2005;14:115764.
  • 14
    Huang S, Afonina I, Miller BA et al. Human papillomavirus types 52 and 58 are prevalent in cervical cancers from Chinese women. Int J Cancer 1997;70:40811.
  • 15
    Lin QQ, Yu SZ, Qu W et al. Human papillomavirus types 52 and 58. Int J Cancer 1998;75:4845.
  • 16
    Lo KW, Cheung TH, Chung TK et al. Clinical and prognostic significance of human papillomavirus in a Chinese population of cervical cancers. Gynecol Obstet Invest 2001;51:2027.
  • 17
    Lo KW, Wong YF, Chan MK et al. Prevalence of human papillomavirus in cervical cancer: a multicenter study in China. Int J Cancer 2002;100:32731.
  • 18
    Peng HQ, Liu SL, Mann V et al. Human papillomavirus types 16 and 33, herpes simplex virus type 2 and other risk factors for cervical cancer in Sichuan Province, China. Int J Cancer 1991;47:7116.
  • 19
    Stephen AL, Thompson CH, Tattersall MH et al. Analysis of mutations in the URR and E6/E7 oncogenes of HPV 16 cervical cancer isolates from central China. Int J Cancer 2000;86:695701.
  • 20
    Yu MY, Tong J, Chan PKS et al. Hypermethylation of the tumor suppressor gene RASSFIA and frequent concomitant loss of heterozygosity at 3p21 in cervical cancers. Int J Cancer 2003;105:2049.
  • 21
    Gao YE, Zhang J, Wu J et al. Detection and genotyping of human papillomavirus DNA in cervical cancer tissues with fluorescence polarization. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai) 2003;35:102934.
  • 22
    Liu J, Rose B, Huang X et al. Comparative analysis of characteristics of women with cervical cancer in high- versus low-incidence regions. Gynecol Oncol 2004;94:80310.
  • 23
    Wu YP, Chen YL, Li LY et al. Associations of high-risk HPV types and viral load with cervical cancer in China. J Clin Virol 2006;35:2649.
  • 24
    Chen SL, Han CP, Tsao YP et al. Identification and typing of human papillomavirus in cervical cancers in Taiwan. Cancer 1993;72:193945.
  • 25
    Chen TM, Chen CA, Wu CC et al. The genotypes and prognostic significance of human papillomaviruses in cervical cancer. Int J Cancer 1994;57:1814.
  • 26
    Lai HC, Sun CA, Yu MH et al. Favorable clinical outcome of cervical cancers infected with human papilloma virus type 58 and related types. Int J Cancer 1999;84:5537.
  • 27
    Yang YC, Shen J, Tate JE et al. Cervical cancer in young women in Taiwan: prognosis is independent of papillomavirus or tumor cell type. Gynecol Oncol 1997;64:5963.
  • 28
    Lin H, Moh JS, Ou YC et al. A simple method for the detection and genotyping of high-risk human papillomavirus using seminested polymerase chain reaction and reverse hybridization. Gynecol Oncol 2005;96:8491.
  • 29
    Yang YY, Koh LW, Tsai JH et al. Correlation of viral factors with cervical cancer in Taiwan. J Microbiol Immunol Infect 2004;37:2827.
  • 30
    Huang LW, Chao SL, Chen PH et al. Multiple HPV genotypes in cervical carcinomas: improved DNA detection and typing in archival tissues. J Clin Virol 2004;29:2716.
  • 31
    Ho CM, Chien TY, Huang SH et al. Integrated human papillomavirus types 52 and 58 are infrequently found in cervical cancer, and high viral loads predict risk of cervical cancer. Gynecol Oncol 2006;102:5460.
  • 32
    Huang HJ, Huang SL, Lin CY et al. Human papillomavirus genotyping by a polymerase chain reaction-based genechip method in cervical carcinoma treated with neoadjuvant chemotherapy plus radical surgery. Int J Gynecol Cancer 2004;14:63949.
  • 33
    Chan MK, Lau KM, Tsui Y et al. Human papillomavirus infection in Hong Kong Chinese women with normal and abnormal cervix—detection by polymerase chain reaction method on cervical scrapes. Gynecol Oncol 1996;60:21723.
  • 34
    Chan PKS, Li WH, Chan MYM et al. High prevalence of human papillomavirus type 58 in Chinese women with cervical cancer and precancerous lesions. J Med Virol 1999;59:2328.
  • 35
    Wu CH, Lee MF, Chang MC et al. Detection of human papillomavirus types in cervical lesions of patients from Taiwan by the polymerase chain reaction. Sex Transm Dis 1994;21:30914.
  • 36
    Lai HC, Sytwu HK, Sun CA et al. Single nucleotide polymorphism at FAS promoter is associated with cervical carcinogenesis. Int J Cancer 2003;103:2215.
  • 37
    Dai M, Bao YP, Li N et al. Human papillomavirus infection in Shanxi Province, People’s Republic of China: a population-based study. Br J Cancer 2006;95:96101.
  • 38
    Li LK, Dai M, Clifford GM et al. Human papillomavirus infection in Shenyang City, People’s Republic of China: a population-based study. Br J Cancer 2006;95:15937.
  • 39
    Asato T, Maehama T, Nagai Y et al. A large case-control study of cervical cancer risk associated with human papillomavirus infection in Japan, by nucleotide sequencing–based genotyping. J Infect Dis 2004;189:182932.
  • 40
    Fujinaga Y, Shimada M, Okazawa K et al. Simultaneous detection and typing of genital human papillomavirus DNA using the polymerase chain reaction. J Gen Virol 1991;72:103944.
  • 41
    Harima Y, Sawada S, Nagata K. Human papilloma virus (HPV) DNA associated with prognosis of cervical cancer after radiotherapy. Int J Radiat Oncol Biol Phys 2002;52:134551.
  • 42
    Ishikawa H, Mitsuhashi N, Sakurai H et al. The effects of p53 status and human papillomavirus infection on the clinical outcome of patients with stage IIIB cervical carcinoma treated with radiation therapy alone. Cancer 2001;91:809.
  • 43
    Kashiwabara K, Nakajima T. Detection of human papillomavirus DNA in invasive cervical cancers by the polymerase chain reaction and its clinical significance. Acta Pathol Jpn 1992;42:87683.
  • 44
    Maki H, Saito S, Ibaraki T et al. Use of universal and type-specific primers in the polymerase chain reaction for the detection and typing of genital human papillomaviruses. Jpn J Cancer Res 1991;82:4119.
  • 45
    Nakagawa S, Yoshikawa H, Onda T et al. Type of human papillomavirus is related to clinical features of cervical carcinoma. Cancer 1996;78:193541.
  • 46
    Nakagawa H, Sugano K, Fujii T et al. Frequent detection of human papilloma viruses in cervical dysplasia by PCR single-strand DNA-conformational polymorphism analysis. Anticancer Res 2002;22:165560.
  • 47
    Saito J, Hoshiai H, Noda K. Type of human papillomavirus and expression of p53 in elderly women with cervical cancer. Gynecol Obstet Invest 2000;49:1903.
  • 48
    Sasagawa T, Basha W, Yamazaki H et al. High-risk and multiple human papillomavirus infections associated with cervical abnormalities in Japanese women. Cancer Epidemiol Biomarkers Prev 2001;10:4552.
  • 49
    Tsuda H, Hashiguchi Y, Nishimura S et al. Relationship between HPV typing and abnormality of G1 cell cycle regulators in cervical neoplasm. Gynecol Oncol 2003;91:47685.
  • 50
    Yamakawa Y, Forslund O, Teshima H et al. Human papillomavirus DNA in adenocarcinoma and adenosquamous carcinoma of the uterine cervix detected by polymerase chain reaction (PCR). Gynecol Oncol 1994;53:1905.
  • 51
    Kanao H, Enomoto T, Ueda Y et al. Correlation between p14 (ARF)/p16(INK4A) expression and HPV infection in uterine cervical cancer. Cancer Lett 2004;213:317.
  • 52
    Nobeyama H, Sumi T, Misugi F et al. Association of HPV infection with prognosis after neoadjuvant chemotherapy in advanced uterine cervical cancer. Int J Mol Med 2004;14:1015.
  • 53
    Nawa A, Nishiyama Y, Kobayashi T et al. Association of human leukocyte antigen-B1*03 with cervical cancer in Japanese women aged 35 years and younger. Cancer 1995;75:51821.
  • 54
    Hwang TS, Jeong JK, Park M et al. Detection and typing of HPV genotypes in various cervical lesions by HPV oligonucleotide microarray. Gynecol Oncol 2003;90:516.
  • 55
    Kim KH, Kim YS. Role of human papillomavirus and p53 tumor suppressor gene in cervical carcinogenesis. Yonsei Med J 1995;36:41225.
  • 56
    Hwang T. Detection and typing of human papillomavirus DNA by PCR using consensus primers in various cervical lesions of Korean women. J Korean Med Sci 1999;14:5939.
  • 57
    Park TC, Kim CJ, Koh YM et al. Human papillomavirus genotyping by the DNA chip in the cervical neoplasia. DNA Cell Biol 2004;23:11925.
  • 58
    An HJ, Kim KR, Kim IS et al. Prevalence of human papillomavirus DNA in various histological subtypes of cervical adenocarcinoma: a population-based study. Mod Pathol 2005;18:52834.
  • 59
    An HJ, Cho NH, Lee SY et al. Correlation of cervical carcinoma and precancerous lesions with human papillomavirus (HPV) genotypes detected with the HPV DNA chip microarray method. Cancer 2003;97:167280.
  • 60
    Cho NH, An HJ, Jeong JK et al. Genotyping of 22 human papillomavirus types by DNA chip in Korean women: comparison with cytologic diagnosis. Am J Obstet Gynecol 2003;188:5662.
  • 61
    Yoshida T, Fukuda T, Sano T et al. Usefulness of liquid-based cytology specimens for the immunocytochemical study of p16 expression and human papillomavirus testing. Cancer 2004;102:1008.
  • 62
    Nagai Y, Maehama T, Asato T et al. Persistence of human papillomavirus infection after therapeutic conization for CIN 3: is it an alarm for disease recurrence? Gynecol Oncol 2000;79:2949.
  • 63
    Yoshikawa H, Kawana T, Kitagawa K et al. Detection and typing of multiple genital human papillomaviruses by DNA amplification with consensus primers. Jpn J Cancer Res 1991;82:52431.
  • 64
    Yoshikawa H, Nagata C, Noda K et al. Human papillomavirus infection and other risk factors for cervical intraepithelial neoplasia in Japan. Br J Cancer 1999;80:6214.
  • 65
    Ichimura H, Yamaguchi S, Kojima A et al. Eradication and reinfection of human papillomavirus after photodynamic therapy for cervical intraepithelial neoplasia. Int J Clin Oncol 2003;8:3225.
  • 66
    Niwa K, Tagami K, Lian Z et al. Topical vidarabine or 5-fluorouracil treatment against persistent HPV in genital (pre)cancerous lesions. Oncol Rep 2003;10:143741.
  • 67
    Hwang HS, Park M, Lee SY et al. Distribution and prevalence of human papillomavirus genotypes in routine pap smear of 2,470 Korean women determined by DNA chip. Cancer Epidemiol Biomarkers Prev 2004;13:21536.
  • 68
    Kim CJ, Jeong JK, Park M et al. HPV oligonucleotide microarray-based detection of HPV genotypes in cervical neoplastic lesions. Gynecol Oncol 2003;89:2107.
  • 69
    Oh LY, Shin JK, Han J et al. Significance of high-risk human papillomavirus detection by polymerase chain reaction in primary cervical cancer screening. Cytopathology 2001;12:7583.
  • 70
    Maehama T. Epidemiological study in Okinawa, Japan, of human papillomavirus infection of the uterine cervix. Infect Dis Obstet Gynecol 2005;13:7780.
  • 71
    Shin HR, Lee DH, Herrero R et al. Prevalence of human papillomavirus infection in women in Busan, South Korea. Cancer 2003;103:41321.
  • 72
    Sajio J, Fukuda T, Hoshiai H et al. High-risk types of human papillomavirus associated with the progression of cervical dysplasia to carcinoma. J Obstet Gynaecol Res 1999;25:2816.
  • 73
    Bhatla N, Dar L, Patro A et al. Human papillomavirus type distribution in cervical cancer in Delhi, India. Int J Gynecol Pathol 2006;25:398402.
  • 74
    Franceschi S, Rajkumar T, Vaccarella S et al. Human papillomavirus and risk factors for cervical cancer in Chennai, India: a case-control study. Int J Cancer 2003;107:12733.
  • 75
    Munirajan AK, Kannan K, Bhuvarahamurthy V et al. The status of human papillomavirus and tumor suppressor genes p53 and p16 in carcinomas of uterine cervix from India. Gynecol Oncol 1998;69:2059.
  • 76
    Sowjanya AP, Jain M, Poli UR et al. Prevalence and distribution of high-risk human papilloma virus(HPV) types in invasive squamous cell carcinoma of the cervix and in normal women in Andhra Pradesh, India. BMC Infectious Diseases 2005;5:116.
  • 77
    Hamkar R, Azad TM, Mahmoodi M et al. Prevalence of human papillomavirus in Mazandaran Province. Islamic Republic of Iran. East Mediterr Health J 2002;8:80511.
  • 78
    Mortazavi S, Zali M, Raoufi M et al. The prevalence of human papillomavirus in cervical cancer in Iran. Asian Pac J Cancer Prev 2002;3:6972.
  • 79
    Franceschi S, Snijders PJF, Arslan A et al. Papillomavirus infection in rural women in Southern India. Br J Cancer 2005;92:6016.
  • 80
    Bhattarakosol P, Lertworapreecha M. Survey of human papillomavirus infection in cervical intraepithelial neoplasia in Thai women. J Med Assoc Thai 2002;85(Suppl. 1):S3605.
  • 81
    Chichareon S, Herrero R, Munoz N et al. Risk factors for cervical cancer in Thailand: a case–control study. J Natl Cancer Inst 1998;90:507.
  • 82
    Siritantikorn S, Laiwejpithaya S, Siripanyaphinyo U et al. Detection and typing of human papillomavirus DNAs in normal cervix, intraepithelial neoplasia and cervical cancer in Bangkok. Southeast Asian J Trop Med Public Health 1997;28:70710.
  • 83
    Settheetham-Ishida W, Kanjanavirojkul N, Kularbkaew C et al. Human papillomavirus genotypes and the p53 codon 72 polymorphism in cervical cancer of Northeastern Thailand. Microbiol Immunol 2005;49:41721.
  • 84
    Sriamporn S, Snijders PJF, Pientong C et al. Human papillomavirus and cervical cancer from a prospective study in Khon Kaen, Northeast Thailand. Int J Gynecol Cancer 2006;16:2669.
  • 85
    Yadav M, Nurhayati ZA, Padmanathan A et al. Polymerase chain reaction detection and restriction enzyme typing of human papillomavirus in cervical carcinoma. Med J Malaysia 1995;50:6471.
  • 86
    Ngelangel C, Munoz N, Bosch FX et al. Causes of cervical cancer in the Philippines: a case–control study. J Natl Cancer Inst 1998;90:439.
  • 87
    Schellekens MC, Dijkman A, Aziz MF et al. Prevalence of single and multiple HPV types in cervical carcinomas in Jakarta, Indonesia. Am J Pathol 2000;157:105562.
  • 88
    Ekalaksananan T, Pientong C, Kotimanusvanij D et al. The relationship of human papillomavirus (HPV) detection to pap smear classification of cervical-scraped cells in asymptomatic women in northeast Thailand. J Obstet Gynaecol Res 2001;27:11724.
  • 89
    Lertworapreecha M, Bhattarakosol P, Niruthisard S. Detection and typing of human papillomavirus in cervical intraepithelial neoplasia grade III in Thai women. Southeast Asian J Trop Med Public Health 1998;29:50711.
  • 90
    Limpaiboon T, Pooart J, Bhattarakosol P. et al. p53 status and human papillomavirus infection in Thai women with cervical carcinoma. Southeast Asian J Trop Med Public Health 2000;31:6671.
  • 91
    Bosch FX. Preface. Vaccine 2006;24(Suppl. 3):vvi.
  • 92
    Clifford GM, Gallus S, Herrero R et al. Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis. Lancet 2005;366:9918.
  • 93
    Clifford GM, Franceschi S, Diaz M et al. Chapter 3: HPV type-distribution in women with and without cervical neoplastic diseases. Vaccine 2006;24(Suppl. 3):S2634.
  • 94
    Woodman CB, Collins S, Rollason TP et al. Human papillomavirus type 18 and rapidly progressing cervical intraepithelial neoplasia. Lancet 2003;361:403.
  • 95
    Schwartz SM, Daling JR, Shera KA et al. Human papillomavirus and prognosis of invasive cervical cancer: a population-based study. J Clin Oncol 2001;19:190615.