| Background:Human papillomavirus(HPV)is the most common sexually transmitted disease in both sexes.Oncogenic HPV infection can cause 57,000 female cancer cases,including cervical,vaginal,vulvar,anal,and oropharyngeal cancers,and 6,000 male cancer cases,including penile,anal,and oropharyngeal cancers.Nononcogenic HPV infection can cause anogenital warts,and its incidences are similar between sexes.The reasons for sex differences in oncogenic and nononcogenic HPV-related diseases are still unknown,which may be caused by different natural history of oncogenic and nononcogenic HPV infection by sex.However,no studies simultaneously recruited men and women to estimate the natural history of multiple anogenital sites by sex.Objectives:To compare the prevalence,incidence,and clearance of anogenital HPV infection in general population by sex,age,and site;to investigate the factors associated with prevalence,incidence and clearance of HPV infection;to assess the risk of sequential acquisition of genital(or anal)HPV infection following a same anal(or genital)HPV infection among men and women;and to estimate the concordance and transmission of HPV infection among different anatomic sites of heterosexual couples.Methods:From May to July 2014,4,687 participants,including 2,309 men and 2,378 women,aged 18-55 years old from the general population in Liuzhou,China were enrolled by advertisement,flyers and posters.A questionnaire was conducted to collect the information on demographic characteristics,hygienic and sexual behaviors,then they were followed-up with 6-month interval for 1 year.On each visit,samples from male penis/glans penis/coronary sulcus(PGC)and perianal/anal canal(PA)specimens and from female vaginal(VA),vulvar(VU)and PA specimens were tested for 16 HPV genotypes(13 oncogenic types,including types 16,18,31,33,35,39,45,51,52,56,58,59 and 68;and 3 nononcogenic types,including types 6,11,and 66)by multicolor real-time PCR.Sex differences in HPV prevalence were compared by using Pearson's x2-test or the Fisher's exact test.The Kappa values were calculated to evaluate the concordance of HPV infection between different sites.Incidence rate ratio(IRR)and clearance rate ratio(CRR)were used to analysis sex differences in incidence and clearance of anogenital HPV infection,respectively.Logistic,Cox and Wei-Lin-Weissfeld Cox regression models were used to analyze the factors associated with prevalence,incidence and clearance of HPV infection,respectivelyResults:1.Prevalence and factors of HPV infection in general population in Liuzhou,ChinaThe prevalence of any oncogenic HPV type was higher in women than in men(18.7%vs 9.4%,p<0.0001),whereas the prevalence of types 6 and I 1 infection was similar by sex(1.4%vs 1.2%,P=0.6832).In both sexes,the five most common oncogenic types were HPV 52,HPV 58,HPV 16,HPV 39 and HPV 18.The prevalence of any HPV in male PGC and PA samples and female VA,VU and PA samples was 10.8%,3.8%,14.2%,13.3%and 8.4%,respectively.The concordance of female VA and VU was highest(Kappa = 0.74),whereas male PGC and PA had the poor concordance(0.14).The prevalence of anogenital HPV infection among women was negatively with age,whereas the prevalence in men was comparable across age.Sexual and hygienic behaviors were associated with HPV infection among men and women2.Incidence,clearance and factors of HPV infection in in general population in Liuzhou,ChinaThe incidence of oncogenic HPV infection was similar in men and women(10.3 and 11,5 per 1,000 person-months,P=0.2745),whereas the incidence of HPV 6/11 infection was higher in men than in women(2.0 versus 1.1,P=0.0176).Men were more likely to clear oncogenic HPV infections than women(101.5 versus 58.6,P<0.0001),but no significant difference was found in the clearance of HPV 6/11 by sex(111.7 versus 84.8,P=0.2662).The incidences of oncogenic HPV in male PA and female PA were 3.5 and 8.6 per 1000 person-months,respectively,with an IRR of 0.41(95%CI,0.30-0.55 for men versus women)(P<0.0001).The CRR of PA oncogenic HPV infection for men versus women was 1.54(95%CI,1.1 7-2.03)(P=0.0022).The incidence rates of any HPV infection were higher in PGC and VA compared to VU(P=0.0005).The clearance rate of HPV infection was higher in PGC than VA or VU(P<0.0001).The incidence of HPV infections was significantly higher in women in the 18-25 years age group than in the older age groups,whereas it did not vary by age among men.3.Sequential acquisition of genital and anal human papillomavirus infection by sex and siteThe risk of acquiring anal infection for any HPV types was higher in both men(HR,2.3;95%CI:1.2-4.4)and women(HR,4,2;95%CI:3.0-5,7)with a preceding concordant genital HPV infection,compared with those without a preceding genital HPV infection.Women had higher genital-to-anal infection for any HPV types than men(RR,3.0;95%CI:1.6-5.6).The RRs of anal-to-genital infection were 0.5(95%CI:0.1-2.0)among men and 1.4(95%CI:0.8-2.4)among women,respectively.4.Prevalence,concordance and transmission of human papillomavirus infection among heterosexual couplesThe HPV type-specific concordance rate between couples was 15.5%(95%CI:8.5-25.0).The concordance number between the male PGC site and female vaginal,vulvar and PA sites were 11,12 and 7,respectively,which were significantly higher than expected by chance.Male-to-female transmission rate(11.5 per 1000 person-month,95%CI:4.3-30.7)was similar to female-to-male transmission rate(11.3 per 1000 person-month,95%CI:5.9-21.7).All infections transmitted from male to female partners originated in male genital,while for female-to-male transmission,the vagina,vulva and PA sites were all involved.Conclusions:There are differences in the natural history of anogenital HPV infection by sex and by HPV type.Oncogenic HPV infections are more likely to process to the persistent infections among women than that among men.Both men and women with prior HPV infection at the first site(genital or anal)had higher risk to sequential acquire same-type HPV infection at the second site(anal or genital),and females seem to have higher risk to get sequential genital-to-anal or anal-to-genital infection.Among couples,the female-to-male HPV transmission rate was similar to the male-to-female rate.In addition to vaginal and vulva,female PA site is also an important reservoir for HPV transmission. |
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