materials were collected from the pathology archives of gachon university gil medical center for the period between 2006 and 2012 . during the six - year period , we collected 10,002 smears examined with hpv analysis as well as papanicolaou staining from female patients in incheon , korea . we retrospectively selected hpv - positive patients based on the results of cytologic and histologic examination . the authors arbitrarily regarded cases comprising less than 6.0% as uncommon and rare hpv genotypes . the total proportion of rare and uncommon hpv genotypes was 44.3% ( 1,666/3,758 ) , however , we excluded the uncommon and rare group 1 hpv genotypes . a total of 404 cases were included in this study , comprised of groups 2a , 2b , 3 , and unclassified hpv genotypes in cases excluding group 1-coinfection . after addition of each genotype of multiple infections , the total number of cases was 447 . according to the carcinogenic potential , hpv types were classified as high risk , low risk , and probably high risk . among the hpv genotypes , only 12 are categorized as carcinogens of the uterine cervix by the working group of the world health organization ( who ) international agency for research on cancer ( iarc).12 hpv genotypes are classified as carcinogens ( group 1 ; hpv16 , 18 , 31 , 33 , 35 , 39 , 45 , 51 , 52 , 56 , 58 , and 59 ) , probable carcinogens ( group 2a ; hpv68 ) , possible carcinogens ( group 2b , hpv26 , 30 , 34 , 53 , 66 , 67 , 69 , 70 , 73 , 82 , 85 , and 97 ) , and not classifiable as to its carcinogenicity to humans ( group 3 ; hpv6 and 11 ) . we used the myhpv chip kit ( mygene co. , seoul , korea ) for detection of hpv . the chip kit was originally able to detect 19 hpv types , and 13 types ( hpv26 , 32 , 53 , 55 , 57 , 59 , 61 , 62 , 66 , 68 , 69 , 70 , and 73 ) were additionally included in may 2010 so the total 32 hpv types in the mygene chip kit included group 1 ( hpv16 , 18 , 31 , 33 , 35 , 39 , 45 , 51 , 52 , 56 , 58 , and 59 ) , group 2a ( hpv 68 ) , group 2b ( hpv26 , 34 , 53 , 66 , 69 , 70 , and 73 ) , and group 3 ( hpv6 and 11 ) . unclassified genotypes ( hpv32 , 40 , 42 , 43 , 44 , 54 , 55 , 57 , 61 , and 62 ) were also detectable . thirty - two oligonucleotide probes ( 5 ' amine , 30-mer sized ) specific for each of the 32 hpv subtypes were fixated . after obtaining fixated dna specimens using a dna isolation kit ( mygene ) , the l1 region , which is the target of hpv dna , was amplified and dyed with indocarbocyanine - dutp using gp5+/gp6+primer . after amplification of hpv dna , 10 ml of the product was denatured for 5 minutes at 95 , and was placed inside the chamber with hybridization solution . the hybridization was performed for 90 minutes at 43 and then washed twice using 2 saline - sodium citrate ( ssc ) with 0.1% sodium dodecyl sulfate for 5 minutes , twice using 0.2 ssc for 5 minutes , and once using 1 ssc for 5 minutes . hybridated hpv dna was detected using a chip scanner ( genepix 4100a , axon instruments , sunnyvale , ca , usa ) . cases showing hpv - negativity by chip scanner but positivity under electrophoresis , i.e. , not specified , were categorized as ' other ' after one repeated examination . we included all specimens on which both papanicolaou cervicovaginal smears and hpv genotyping were performed . the pathologic results of smears , punch biopsy , or conization at the time of hpv genotyping were reviewed . the highest grade of diagnosed pathology was attached to the associated hpv type because of predictable variable errors , including histologic and/or cytologic under- or over - diagnoses . in this study , we analyzed cases showing reactive or inflammatory pathology as within normal limits ( wnl ) . data analysis was performed using spss ver . 17.0 ( spss inc . , chicago , il , usa ) . for estimation of the hpv genotype distribution , multiple hpv infections were considered separately . here , we evaluated genotype - specific hpv prevalence , however , hpv - positive cases with multiple co - infections by group 1 were not counted . a stratified analysis of the relative overall hpv and genotype - specific contribution according to patient age at diagnosis and histological characteristics was performed using pearson chi - square test and fisher 's exact test . to eliminate the bias of the small sample size , we set the number of each group to over 20 for statistical analysis . materials were collected from the pathology archives of gachon university gil medical center for the period between 2006 and 2012 . during the six - year period , we collected 10,002 smears examined with hpv analysis as well as papanicolaou staining from female patients in incheon , korea . we retrospectively selected hpv - positive patients based on the results of cytologic and histologic examination . the authors arbitrarily regarded cases comprising less than 6.0% as uncommon and rare hpv genotypes . the total proportion of rare and uncommon hpv genotypes was 44.3% ( 1,666/3,758 ) , however , we excluded the uncommon and rare group 1 hpv genotypes . a total of 404 cases were included in this study , comprised of groups 2a , 2b , 3 , and unclassified hpv genotypes in cases excluding group 1-coinfection . after addition of each genotype of multiple infections , the total number of cases was 447 . according to the carcinogenic potential , hpv types were classified as high risk , low risk , and probably high risk . among the hpv genotypes , only 12 are categorized as carcinogens of the uterine cervix by the working group of the world health organization ( who ) international agency for research on cancer ( iarc).12 hpv genotypes are classified as carcinogens ( group 1 ; hpv16 , 18 , 31 , 33 , 35 , 39 , 45 , 51 , 52 , 56 , 58 , and 59 ) , probable carcinogens ( group 2a ; hpv68 ) , possible carcinogens ( group 2b , hpv26 , 30 , 34 , 53 , 66 , 67 , 69 , 70 , 73 , 82 , 85 , and 97 ) , and not classifiable as to its carcinogenicity to humans ( group 3 ; hpv6 and 11 ) . we used the myhpv chip kit ( mygene co. , seoul , korea ) for detection of hpv . the chip kit was originally able to detect 19 hpv types , and 13 types ( hpv26 , 32 , 53 , 55 , 57 , 59 , 61 , 62 , 66 , 68 , 69 , 70 , and 73 ) were additionally included in may 2010 so the total 32 hpv types in the mygene chip kit included group 1 ( hpv16 , 18 , 31 , 33 , 35 , 39 , 45 , 51 , 52 , 56 , 58 , and 59 ) , group 2a ( hpv 68 ) , group 2b ( hpv26 , 34 , 53 , 66 , 69 , 70 , and 73 ) , and group 3 ( hpv6 and 11 ) . unclassified genotypes ( hpv32 , 40 , 42 , 43 , 44 , 54 , 55 , 57 , 61 , and 62 ) were also detectable . thirty - two oligonucleotide probes ( 5 ' amine , 30-mer sized ) specific for each of the 32 hpv subtypes were fixated . after obtaining fixated dna specimens using a dna isolation kit ( mygene ) , the l1 region , which is the target of hpv dna , was amplified and dyed with indocarbocyanine - dutp using gp5+/gp6+primer . after amplification of hpv dna , 10 ml of the product was denatured for 5 minutes at 95 , and was placed inside the chamber with hybridization solution . the hybridization was performed for 90 minutes at 43 and then washed twice using 2 saline - sodium citrate ( ssc ) with 0.1% sodium dodecyl sulfate for 5 minutes , twice using 0.2 ssc for 5 minutes , and once using 1 ssc for 5 minutes . hybridated hpv dna was detected using a chip scanner ( genepix 4100a , axon instruments , sunnyvale , ca , usa ) . cases showing hpv - negativity by chip scanner but positivity under electrophoresis , i.e. , not specified , were categorized as ' other ' after one repeated examination . we included all specimens on which both papanicolaou cervicovaginal smears and hpv genotyping were performed . the pathologic results of smears , punch biopsy , or conization at the time of hpv genotyping were reviewed . the highest grade of diagnosed pathology was attached to the associated hpv type because of predictable variable errors , including histologic and/or cytologic under- or over - diagnoses . in this study , we analyzed cases showing reactive or inflammatory pathology as within normal limits ( wnl ) . we evaluated genotype - specific hpv prevalence , however , hpv - positive cases with multiple co - infections by group 1 were not counted . a stratified analysis of the relative overall hpv and genotype - specific contribution according to patient age at diagnosis and histological characteristics was performed using pearson chi - square test and fisher 's exact test . to eliminate the bias of the small sample size , we set the number of each group to over 20 for statistical analysis . a total of 447 cases comprised groups 2a , 2b , 3 , and unclassified hpv genotypes in cases excluding group 1-coinfection ( table 1 ) . one hundred one cases were lsils ( 25.0% ) , 33 cases were hsils ( 8.2% ) , and 11 cases were ics ( 2.7% ) . among them , 64.1% showed normal cytologic or histologic diagnosis ( 259/447 ) . in a comparison of the normal group versus abnormal groups ( lsil , hsil , and ic ) between group 2 , unclassified group , and hpv16/hpv6 , 11 cases were statistically significant ( relative risk [ rr ] , 1.397 ; p<.001 and rr , 2.616 ; p<.001 , respectively ) , irrespective of group 1-coinfections . wnl and lsil versus cases of higher grade than lsil between group 2 , unclassified group , and hpv16 were statistically significant ( rr , 3.191 ; p<.001 ) , while differences were not significant between group 2 , unclassified group , and hpv6 and 11 ( p=.19 ) ( table 2 ) . there were three hpv6-infected cases , which were shown to be hsil . at the time of diagnosis , we re - tested the hpv typing using the same samples and got concordant results . one case involved a 46-year - old female who was diagnosed as having atypical squamous cells , which could not be excluded as being hsil on papanicolaou cervicovaginal smears , and moderate dysplasia on punch biopsy . she underwent a hysterectomy , and the diagnosis was severe dysplasia on the cervix . during 14 months of follow - up , there was no evidence of disease recurrence . the other 2 cases were from the same patient , a 32-year - old female . the first time , she was diagnosed as having hsil by papanicolaou cervicovaginal smears , and chronic cervicitis on punch biopsy . the results of these repeated examinations were that there was hsil by papanicolaou cervicovaginal smears and a persistent hpv6 infection . she underwent conization , and the diagnosis was squamous cell carcinoma in situ with clear resection margin . during 3 months of follow - up , the results of papanicolaou cervicovaginal smears and hpv typing were all negative . in the groups 2a , 2b , and unclassified , 35.6% ( 159/447 ) of uncommon hpv genotypes - hpv68 , 26 , 34 , 53 , 66 , 69 , 70 , 73 , 32 , 40 , 42 , 43 , 44 , 54 , 55 , 57 , 61 , and 62-infected cases showed lsils , hsils , and ics ; 2.7% ( 12/447 ) showed an association with ics , 7.8% ( 35/447 ) showed an association with hsils , and 25.1% ( 112/447 ) showed an association with lsils . lsils , hsils , and ics were detected in cases involving hpv68 ( 17/32 , 53.1% ) , hpv42 ( 4/8 , 50.0% ) , hpv53 ( 39/89 , 43.8% ) , hpv40 ( 11/26 , 42.3% ) , hpv66 ( 17/43 , 40.0% ) , hpv54 ( 19/49 , 38.8% ) , hpv43 ( 3/8 , 37.5% ) , and hpv70 ( 38/104 , 36.5% ) . the rare and uncommon types showing a statistical relationship with lsils , hsils , and ics compared to hpv6 and 11 were as follows : hpv68 ( p<.001 ) , hpv53 ( p=.001 ) , hpv40 ( p=.01 ) , hpv66 ( p=.01 ) , hpv54 ( p=.01 ) , and hpv70 ( p=.01 ) . hpv68 ( rr , 3.453 ) showed the highest the value of relative risk followed by hpv53 ( rr , 2.848 ) , hpv40 ( rr , 2.750 ) , hpv66 ( rr , 2.570 ) , hpv54 ( rr , 2.520 ) , and hpv70 ( rr , 2.375 ) ( table 3 ) . the rare and uncommon types showing a statistical relationship with lsils , hsils , and ics compared to hpv16 were as follows : hpv68 ( rr , 1.059 ; p=.73 ) , hpv53 ( rr , 1.284 ; p=.03 ) , hpv40 ( rr , 1.330 ; p=.16 ) , hpv66 ( rr , 1.423 ; p=.03 ) , hpv54 ( rr , 1.451 ; p=.02 ) , and hpv70 ( rr , 1.539 ; p<.001 ) . differences between hpv16 and hpv53 , 66 , 54 , and 70 genotypes were statistically significant , however , the value of the relative risk of hpv66 showed no significance ( table 4 ) . out of 659 cases of ' other ' hpv - positive cases , 22.6% ( 149/659 ) were accompanied by hsil and ic . these other types showed statistical significances with hsils and ics , compared to hpv6 and 11 ( p=.01 ) . coinfection with multiple hpv genotypes was observed in 15.7% ( 497/3,164 ) of hpv - infected patients . cases infected with two types , three types , four types , and more than five types were 13.3% ( 421/3,164 ) , 1.9% ( 59/3,164 ) , 0.4% ( 14/3,164 ) , and 0.1% ( 3/3,164 ) , respectively . after exclusion of group 1 genotypes , the hpv genotypes affected by multiple infections were 8.2% ( 37/447 ) . there were 6 cases in hsils or ics : hpv40/53 ( n=2 ) , hpv54/68 ( n=2 ) , hpv40/55 ( n=1 ) , and hpv53/66 ( n=1 ) . a total of 447 cases comprised groups 2a , 2b , 3 , and unclassified hpv genotypes in cases excluding group 1-coinfection ( table 1 ) . one hundred one cases were lsils ( 25.0% ) , 33 cases were hsils ( 8.2% ) , and 11 cases were ics ( 2.7% ) . among them , 64.1% showed normal cytologic or histologic diagnosis ( 259/447 ) . in a comparison of the normal group versus abnormal groups ( lsil , hsil , and ic ) between group 2 , unclassified group , and hpv16/hpv6 , 11 cases were statistically significant ( relative risk [ rr ] , 1.397 ; p<.001 and rr , 2.616 ; p<.001 , respectively ) , irrespective of group 1-coinfections . wnl and lsil versus cases of higher grade than lsil between group 2 , unclassified group , and hpv16 were statistically significant ( rr , 3.191 ; p<.001 ) , while differences were not significant between group 2 , unclassified group , and hpv6 and 11 ( p=.19 ) ( table 2 ) . there were three hpv6-infected cases , which were shown to be hsil . at the time of diagnosis , we re - tested the hpv typing using the same samples and got concordant results . one case involved a 46-year - old female who was diagnosed as having atypical squamous cells , which could not be excluded as being hsil on papanicolaou cervicovaginal smears , and moderate dysplasia on punch biopsy . she underwent a hysterectomy , and the diagnosis was severe dysplasia on the cervix . during 14 months of follow - up , there was no evidence of disease recurrence . the other 2 cases were from the same patient , a 32-year - old female . the first time , she was diagnosed as having hsil by papanicolaou cervicovaginal smears , and chronic cervicitis on punch biopsy . the results of these repeated examinations were that there was hsil by papanicolaou cervicovaginal smears and a persistent hpv6 infection . she underwent conization , and the diagnosis was squamous cell carcinoma in situ with clear resection margin . during 3 months of follow - up , the results of papanicolaou cervicovaginal smears and hpv typing were all negative . in the groups 2a , 2b , and unclassified , 35.6% ( 159/447 ) of uncommon hpv genotypes - hpv68 , 26 , 34 , 53 , 66 , 69 , 70 , 73 , 32 , 40 , 42 , 43 , 44 , 54 , 55 , 57 , 61 , and 62-infected cases showed lsils , hsils , and ics ; 2.7% ( 12/447 ) showed an association with ics , 7.8% ( 35/447 ) showed an association with hsils , and 25.1% ( 112/447 ) showed an association with lsils . lsils , hsils , and ics were detected in cases involving hpv68 ( 17/32 , 53.1% ) , hpv42 ( 4/8 , 50.0% ) , hpv53 ( 39/89 , 43.8% ) , hpv40 ( 11/26 , 42.3% ) , hpv66 ( 17/43 , 40.0% ) , hpv54 ( 19/49 , 38.8% ) , hpv43 ( 3/8 , 37.5% ) , and hpv70 ( 38/104 , 36.5% ) . the rare and uncommon types showing a statistical relationship with lsils , hsils , and ics compared to hpv6 and 11 were as follows : hpv68 ( p<.001 ) , hpv53 ( p=.001 ) , hpv40 ( p=.01 ) , hpv66 ( p=.01 ) , hpv54 ( p=.01 ) , and hpv70 ( p=.01 ) . hpv68 ( rr , 3.453 ) showed the highest the value of relative risk followed by hpv53 ( rr , 2.848 ) , hpv40 ( rr , 2.750 ) , hpv66 ( rr , 2.570 ) , hpv54 ( rr , 2.520 ) , and hpv70 ( rr , 2.375 ) ( table 3 ) . the rare and uncommon types showing a statistical relationship with lsils , hsils , and ics compared to hpv16 were as follows : hpv68 ( rr , 1.059 ; p=.73 ) , hpv53 ( rr , 1.284 ; p=.03 ) , hpv40 ( rr , 1.330 ; p=.16 ) , hpv66 ( rr , 1.423 ; p=.03 ) , hpv54 ( rr , 1.451 ; p=.02 ) , and hpv70 ( rr , 1.539 ; p<.001 ) . differences between hpv16 and hpv53 , 66 , 54 , and 70 genotypes were statistically significant , however , the value of the relative risk of hpv66 showed no significance ( table 4 ) . out of 659 cases of ' other ' hpv - positive cases , 22.6% ( 149/659 ) were accompanied by hsil and ic . these other types showed statistical significances with hsils and ics , compared to hpv6 and 11 ( p=.01 ) . coinfection with multiple hpv genotypes was observed in 15.7% ( 497/3,164 ) of hpv - infected patients . cases infected with two types , three types , four types , and more than five types were 13.3% ( 421/3,164 ) , 1.9% ( 59/3,164 ) , 0.4% ( 14/3,164 ) , and 0.1% ( 3/3,164 ) , respectively . after exclusion of group 1 genotypes , the hpv genotypes affected by multiple infections were 8.2% ( 37/447 ) . there were 6 cases in hsils or ics : hpv40/53 ( n=2 ) , hpv54/68 ( n=2 ) , hpv40/55 ( n=1 ) , and hpv53/66 ( n=1 ) . hpvs are epitheliotrophic viruses that predominantly infect mucocutaneous tissue , including the uterine cervix.4 despite screening based on a national cervical cancer screening program and recent introduction of hpv vaccination , uterine cervical cancer is the second most common female malignancy worldwide.1,13 cervical cancer remains a major health burden in korea.2,5 according to the carcinogenic potential , hpv types were classified as high risk , low risk , and probably high risk . among the hpv genotypes , only 12 are categorized as carcinogens of the uterine cervix by the working group of the world health organization ( who ) international agency for research on cancer ( iarc).12 hpv genotypes are classified as carcinogens ( group 1 ; hpv16 , 18 , 31 , 33 , 35 , 39 , 45 , 51 , 52 , 56 , 58 , and 59 ) , probable carcinogens ( group 2a ; hpv68 ) , possible carcinogens ( group 2b , hpv26 , 30 , 34 , 53 , 66 , 67 , 69 , 70 , 73 , 82 , 85 , and 97 ) , and not classifiable as to its carcinogenicity to humans ( group 3 ; hpv6 and 11 ) . however , a recent worldwide assessment of hpv genotypes revealed that the previously unknown uncommon hpv types , which were identified as types 26 , 30 , 61 , 67 , 69 , 82 , and 91 , were identified in 1% of all studied ics , although the biological behaviors of these rare genotypes have not yet been fully clarified due to insufficient epidemiological research.14,15 in this study , we focused on the correlation of dysplasia or ic with rare and uncommon hpv genotypes to clarify the importance of these uncommon genotypes associated with uterine cervical dysplasia and carcinogenesis . in our study of the previously unnoticed rare and uncommon hpv genotypes , significant differences were observed between hpv16 and group 2/ unclassified group , except for group 1-coinfection . significant differences were observed between group 2/ unclassified group and group 3 only when compared between the normal group and the cervical intraepithelial neoplasm . hpv 68 ( group 2a ) is closely related to hpv39 , 70 , 59 , 45 , and 18.4,10 these types belong to the alpha-7 species , associated with high - risk mucosal lesions , and all genotypes in these alpha-7 species were categorized as group 1 , except for hpv68 and 70.4 according to our results , hpv68 was statistically different from group 3 , however , it did not show a difference with group 1 in the pathogenesis of hsil and ics . especially , the possibility of cervical intraepithelial neoplasms was 3.453 times higher with hpv68 than with hpv6 and 11 . these results suggest that hpv genotype may take similar carcinogenic significance in cervical carcinogenesis as the previous study and surveys revealed . hpv70 was statistically different with wnl versus abnormal findings compared to hpv16 or group 3 ( p<.001 and p=.01 , respectively ) . according to the previous data , identification of hpv70 is relatively infrequent in normal and cancer patients , with a higher prevalence seen in precancerous lesions.10,16 the relatively high incidence of lsil in hpv70 infection was seen in this study , as was seen in previous studies.10,16 hpv53 showed a significant increase in prevalence from 1990 - 1999 to 2006 - 2010.11,15,17 in this study , hpv53 was the genotype with the second highest prevalence ( 3.5% ) among the rare and uncommon types , and showed the second highest incidence among the rare and uncommon hpv types in hsils and ics ( 13/89 , 14.6% ) , followed by hpv68 , excluding group 1-coinfection . a significant difference was observed in group 3 ( p=.001 ) , and the value of relative risk was the second highest among uncommon and rare hpvs ( rr , 2.848 ) . a difference in abnormal finding was also observed between hpv53 and that of hpv16 , however , the value of relative risk in hpv16 was lower than that of group 3 ( rr , 1.284 ) . these results suggest a relatively high incidence of lsil with hpv53 , as is seen with hpv70 infection.18 untreated lsil could worsen or progress to persistent lsil , and has been reported to occur in 29.7% of cases.13 for this reason , awareness of lsil in hpv53 or hpv70 infection is needed . coinfection with multiple hpv genotypes is commonly encountered in hpv studies.6,8 - 11,15 the reported prevalences of multiple genotype infection span a broad range , from 4.4% to 78.3%.15 furthermore , the carcinogenic effects of multiple infections are still debatable . a high incidence of coinfection by multiple genotypes ( 15.7% ) was observed in this study , which might have been affected by the sensitivity of the hpv dna array system , the characteristics of the study population , and geographic distribution.19 watari et al.7 reported that coinfection with hpv34 could prevent tumor progression of invasive squamous cell carcinoma with hpv16 . however , according to the study reported by lee et al.,20 multiple infection showed a 31.8-fold higher risk of cervical cancer , while the single hpv type showed a 19.9-fold increased risk compared to no hpv infection . we found that multiple infections were statistically different from single infections ( p<.001 ) , in that they were more prevalent in hsils and ics . these results were expected because most hsils and ics in multiple infections involved high risk hpv ( 133/139 , 95.7% ) . however , previous studies on the relationship between infection by multiple hpv genotypes and cervical carcinogenesis have reported inconsistent and controversial results and subsequent possible influence of group 1 , the most powerful carcinogens , on evaluation of these uncommon and rare hpv genotypes . therefore , we excluded those types of cases from this study . additional studies will be needed in order to determine the association between multiple infections and pathogenesis . a previous study reported the detection of hpv dna in up to 89.1% of ic cases when on the basis of formalin - fixed paraffin - embedded blocks,8 and that rate is similar to the one identified in our study ( 204/245 , 85.3% ) . we also found that 2.4% ( 92/3,758 ) of uncommon groups 2a , 2b , 3 , and unclassified genotypes showed hsils and ics , whereas 7.9% ( 298/3,758 ) of group 1 genotypes , except for hpv16 , 18 , and 58 , showed hsils and ics , similar to rates found by the survey on the previously unknown hpv types that comprised 1% of all studied ics , such as hpv26 , 30 , 61 , 67 , 69 , 82 , and 91.14 the dna microarray ( dna chip ) method that we used is widely available for clinical use due to its relatively simplified and quick method , its use of both fresh and paraffin samples with high sensitivity , and its capacity for detection of single and multiple coinfections of hpv at once.19 out of 659 cases of other types , 22.6% ( 149/659 ) were hsil and ic , which can not be detected by this method and may influence the results of this study . despite low prevalence and less potency rare and uncommon hpv type , this paper might provide clues for the closeness of the link between rare and uncommon hpv type , carcinogenicity , and invasive cervical carcinomas . unlike women with hpv infection , the age of patients with ics related to hpv16 , 18 , or 58 is not different from that of ic patients infected with rare and uncommon hpv types . two recently developed vaccines , the recombinant quadrivalent hpv vaccine ( gardasil , merck ) , mainly prevents the hpv targeting types 16 , 18 , 6 , 11 , and 31 , while the bivalent hpv recombinant vaccine ( cervarix , glaxosmithkline ) mainly prevents the hpv targeting types 16 , 18 , 45 , and 31.21 as shown in the end - of - study analysis of patricia , the hpv16 and 18 vaccine provides cross - protective efficacy against six - month persistent infection and moderate to severe dysplasia or ic associated with hpv31 , 33 , 45 , and 51 , although gardasil showed slightly less potency for cross - protection . even if clinical trials of prophylactic vaccines targeted for hpv16 and 18 showed drastically preventive effects for hpv infection and precancerous lesions , the possibility of cross - protection against other hpv genotypes,21 especially uncommon and rare hpv genotypes , is extremely important but remains unsolved . because hpv genotypes share structural similarities , the vaccines may protect against hpv types other than these targeted types . however , detailed and targeted developed vaccine may be required . in summary , we found that uncommon and rare hpv genotypes may provide incremental etiologic contributions in cervical carcinogenesis , especially hpv68 , 70 , and 53 . the rare and uncommon hpv genotypes are correlated with cervical carcinogenesis as well as well known , established high - risk hpv genotypes . the results of our study may be helpful in formulating a strategy for further second - generation vaccine development in a particular region . we emphasize that future studies should also focus on these rare uncommon hpv genotypes , especially on the different distributions of these rare hpv genotypes in particular regions .
backgroundhuman papillomavirus ( hpv ) is an oncogenic virus in cervical cancer and most invasive carcinomas ( ics ) are caused by hpv16 and 18 . 
 however , the roles and contributions of other uncommon and rare genotypes remain uncertain.methodshpv genotypes were retrospectively assessed using an hpv dna chip that can specify up to 32 hpv genotypes . 
 we arbitrarily regarded genotypes accounting for less than 6% of the total as uncommon and rare genotypes.resultsa total of 3,164 hpv - positive cases were enrolled . in groups 2a , 
 2b , 3 , and unclassified hpv genotypes , 2.4% of cases with uncommon hpv genotypes ( 68 , 26 , 34 , 53 , 66 , 69 , 70 , 73 , 40 , 42 , 43 , 44 , 54 , 55 , 61 , 62 , 6 , and 11 ) showed high grade squamous intraepithelial lesions and ics . 
 there were no hpv32- and 57-infected cases.conclusionswe found that the uncommon and rare hpv genotypes may provide incremental etiologic contributions in cervical carcinogenesis , especially hpv68 , 70 , and 53 . 
 further studies on these uncommon and rare hpv genotypes will be of importance in establishing the significance of genotypes in different regions , especially in planning a strategy for further vaccine development as well as follow - up on the effectiveness of the currently used vaccines .