cervical carcinoma is the second most prevalent cancer in the world , and the most common female cancer in sub - saharan africa . infection with high - risk human papillomavirus ( hr - hpv ) is the main risk factor for the development of cervical carcinoma . hiv - positive women are reported to be almost twice as likely to be concurrently infected with hpv than hiv - negative women . recently introduced hpv vaccines against genotypes 16 and 18 are designed to prevent about 70% of cervical cancers . the relevance of these genotypes to women in other parts of the world has been questioned , with a study of hpv genotypes in women in 38 countries including some in central america , africa , asia , and oceania . in this study , hr - hpv types 16 and 18 were detected in 71% of cases of invasive cervical cancer . of the cases of invasive cervical cancer from africa , hr - hpv 16 and 18 were detected , respectively , in 48% and 23% of cases that were positive for hpv dna . there are limited data on hr - hpv genotypes among hiv - positive women in africa , and little is known about their relationship with cervical cytology in these populations . we carried out a study to determine the prevalence of hpv genotypes among hiv - positive women in africa with normal and abnormal cervical cytology scores . cervical samples were collected from women attending the hiv treatment clinic of sekou - toure regional hospital and surrounding hospitals in mwanza , tanzania between february and march 2010 , as part of a randomized controlled trial . eligible subjects were nonpregnant , hiv - positive females , over 18 years of age who had used antiretroviral therapy ( art ) for at least 6 months . subjects were excluded if pregnant , breastfeeding , intolerant to lactose or fermented milk . in total 168 tanzanian women were included in the study , of whom 143 women had cervical swabs adequate for hpv testing at baseline . the medical research coordinating committee of the national institute for medical research , tanzania , approved the study design and protocol . participants were informed of the purpose of the study and gave their signed or thumb - printed informed consent before participation ( clinicaltrials.gov identifier : nct01258556 ) . cervical samples collected in 2008 from hiv - positive women attending the ndlovu medical centre in elandsdoorn in moutse district , south africa , were also included in this analysis . in total , 51 women testing positive for hiv were included . information was provided to the study participants and oral consent was obtained by the doctors for a cervical sample to be examined . none of the hiv - positive women were receiving art at the time of sample collection . cervical samples from all participants were collected by a clinician using a standard sampling brush , and placed into a vial with coagulant fixative boonfix , which consists of ethyl alcohol , low molecular weight peg , and acetic acid . the fixed samples , coded by a method that did not disclose any subject names , were sent to the leiden cytology and pathology laboratory ( lcpl ) in the netherlands for analysis [ 5 , 6 ] . a thinprep cytology slide was made of the boonfixed samples , and stained with the papanicolaou method . the cytology thinprep slides were classified according to the bethesda classification system as wnl ( within normal limits ) , ascus or lsil ( atypical squamous cells of undetermined significance and low - grade squamous intraepithelial lesions ) , or hsil ( high - grade squamous intraepithelial lesions ) . of the cases with an abnormal cytology score ( ascus , lsil , and hsil ) , the residue of the cervical sample was used to prepare histologic paraffin slides [ 7 , 8 ] . the purification of dna from the boonfix solution was performed in the biorobot m48 , qiagen ( germany ) , which uses the magattract dna mini m48 kit . samples were analyzed using a sensitive spf 10 pcr - reverse hybridization line probe assay ( innogenetics , belgium ) . this system is based on pcr of part of the l1 region of the hpv genome , which is amplified using spf10 primers . this strip included 14  hr - hpv types ( 16 , 18 , 31 , 33 , 35 , 39 , 45 , 51 , 52 , 56 , 58 , 59 , 66 , and 68 ) . low risk ( lr ) and undetermined hpv types are differentiated into 13 types ( 6 , 11 , 26 , 40 , 43 , 44 , 53 , 54 , 69 , 70 , 73 , 74 , and 82 ) . type - specific hpv prevalence was compared between women with hsil , lsil , and wnl . the chi - square test was used to test for significant associations between country and hpv type . one hundred three ( 72% ) tanzanian women and 35 ( 69% ) south african women had a normal cytology score ( wnl ) ( table 1 ) . nine ( 6% ) tanzanian women and 8 ( 16% ) south african women had hsil . examples of cases with an abnormal cytology score are presented in figure 1 . overall , 109 ( 56% ) women tested positive for hr - hpv ( table 2 ) ; 80 ( 56% ) tanzanian women and 29 ( 57% ) south african women . seventy - six ( 53% ) tanzanian women and 30 ( 59% ) south african women tested positive for a lr - hpv or undetermined hpv type . among women testing positive for hpv , the mean age was 35.4 years ( range : 2052 ) in south africa and 40.5 years ( range : 2573 ) in tanzania . overall , the most prevalent hr - hpv subtypes were hr - hpv 16 ( 26% ) and hr - hpv 52 ( 30% ) , and the prevalence of hr - hpv genotypes varied by country . among tanzanian women testing positive for any hr - hpv , the most common genotype was hr - hpv 52 ( 35% ) , followed by hr - hpv 16 ( 23% ) and hr - hpv 66 ( 20% ) . in contrast , among south african women testing positive for any hr - hpv , the most common genotype was hr - hpv 16 ( 34% ) , followed by hr - hpv 35 ( 24% ) , hr - hpv 18 ( 21% ) , hr - hpv 33 ( 21% ) , and hr - hpv 66 ( 21% ) . genotypes 18 and 35 were significantly more common in south africa than tanzania ; the prevalence of genotype 18 was 21% in south africa compared to 4% in tanzania ( p - value = 0.01 ) , and the prevalence of hr - hpv 35 was 24% in south africa and 8% in tanzania ( p - value = 0.03 ) ( figure 3(a ) ) . the most prevalent lr - hpv subtype overall was hr - hpv 44 ( 22% ) ( figure 3(b ) ) . all women with abnormal cytology ( ascus , lsil , or hsil ) had detectable hpv ( table 2 ) . ninety - four percent ( 16/17 ) of women with hsil , 90% ( 35/39 ) of women with lsil , and 42% ( 58/138 ) of women within normal limits ( wnl ) tested positive for hr - hpv . women with hsil were more likely to test positive for hr - hpv 16 compared to women with normal cytology ( wnl ) ( 29% versus 6% , p < 0.01 ) . hr - hpv 18 was found in only 11.8% of women with hsil ( table 3 ) and the prevalence varied by country ; the prevalence of hr - hpv 18 was 4% in tanzania compared to 21% in south africa ( p - value = 0.01 ) . this study found that hr - hpv genotypes not included in the currently licensed hpv vaccines are highly prevalent in hiv - positive women from tanzania and south africa . as expected , among women with hr - hpv the prevalence of hr - hpv 16 was high ( 26% ) .    despite the high rate of abnormal cytology among women in tanzania , in contrast , hr - hpv 18 was significantly more common among south african women with abnormal cytology ( 21% ) . we also found significant regional differences in the prevalence of hr - hpv 35 ; the prevalence of hr - hpv 35 was 8% among tanzanian women compared to 24% for south african women . in rural mozambique , castellsagu et al . also found a high prevalence of hr - hpv 35 ( 17% among hpv - positive women , and 30% among women with cervical neoplasia ) , compared to an hr - hpv 35 prevalence of 5% found by sanjose in other african women with cervical neoplasia ( algeria , mozambique , nigeria , and uganda ) . the hr - hpv 52 prevalence found in this study ( 35% of tanzanian women and 17% of south african women with any hpv ) is vastly different from that in women in the netherlands ( 5.5% ) . a study in pretoria , south africa reported an hr - hpv 52 prevalence of 6% among women with cervical preneoplasia . in the general female population in macao , and northern taiwan , hr - hpv 52 was the most common genotype found , while in east asia it was among the top five detected [ 1315 ] . the prevalence of hr - hpv 45 was low in our cohort ( figure 3(a ) ) , as also found by others in women with preneoplastic lesions . however , hr - hpv 45 is the third most common hpv type in invasive cervical cancer worldwide . the early presentation of cases of invasive cervical cancer that are positive for hr - hpv 45 might be related to a short time for progression to invasive cancer , with or without transition through the preneoplastic stages , possible correlated to a high early integration rate . the strengths of our study include using a standardized hpv type - specific pcr protocol and cytology diagnosis across the two sites . there were differences between the women studied that may have contributed to the different prevalence estimates of hr - hpv types . in contrast , the women in south africa were recently diagnosed with hiv and not yet eligible for art . in hiv positive women there is less hpv clearance due to a lack of an appropriate immune response . the impact of art in hpv infection and cervical cancer still needs to be defined . a limitation of this study is that no additional information from the south african women is known about their sexual behavior , and therefore we were unable to explore associations between behaviors and hpv genotype . roteli - martins et al . found that young age at first sexual intercourse and increasing number of sexual partners is the main determinant for hr - hpv 16/18 infections . for an hpv vaccine to effectively reduce incidence of cervical cancer , it will need to protect against the major hr - hpv infection types progressing to cervical cancer . because infection types may vary across settings and ethnicities , the impact a vaccine has in preventing cancer in particular settings needs to be considered . in this study , hr - hpv16 was found in 29% of women diagnosed with hsil ; however , hr - hpv 18 was only found in 11% . certainly the high prevalence of hr - hpv found here and reported by others ,   emphasizes the importance of screening for cervical cancer especially in developing countries with high rates of hiv . because more than one - third ( 42% ) of women with normal cytology in this study tested positive for an hr - hpv type , as also found by bruni and others , hpv - based screening tests in this population would be highly inefficient unless coupled with cytology screening of the hpv positive sample .   in summary , the present study showed some differences in the prevalence of hpv genotypes among hiv - positive women in two african countries , and an overall high hpv prevalence . the differences found in hr - hpv genotypes warrant the need to consider different monitoring programmes for cervical preneoplasia , especially in hiv - positive women .
background . 
 there are limited data on high - risk human papillomavirus ( hr - hpv ) genotypes among hiv - positive women in africa , and little is known about their relationship with cervical cytology in these populations . methods . 
 we conducted a cross - sectional study among 194 hiv - positive women ( 143 from tanzania , and 51 from south africa ) to evaluate hpv genotypes among hiv - positive women with normal and abnormal cytology . 
 cervical samples were genotyped for hpv types , and slides were evaluated for atypical squamous cell changes according to the bethesda classification system . 
 results . 
 prevalence of high grade squamous intraepithelial dysplasia ( hsil ) was 9% . 
 overall , more than half ( 56% ) of women were infected with an hr - hpv type ; 94% of women with hsil ( n = 16 ) , 90% of women with lsil 
 ( n = 35 ) , and 42% of women within normal limits ( wnl ) 
 ( n = 58 ) tested positive for hr - hpv . 
 overall , the most prevalent hr - hpv subtypes were hpv16 ( 26% ) and hpv52 ( 30% ) . 
 regional differences in the prevalence of hpv18 and hpv35 were found . 
 conclusion . 
 regional differences in hpv genotypes among african women warrant the need to consider different monitoring programmes for cervical preneoplasia . 
 hpv - based screening tests for cervical preneoplasia would be highly inefficient unless coupled with cytology screening of the hpv - positive sample , especially in hiv - positive women .