In the last decade, the inclusion of HPV DNA testing in cervical cancer screening has provided one of the best strategies for the prevention and timely detection of HPV. We conducted a high-throughput HPV genotyping study based on MALDI-TOF mass spectrometry to determine the prevalence of 24 HPV genotypes, including oncogenic genotypes, in Mexican women and correlated the results with cytological findings and clinical variables. We likewise identified the risk factors in patients with the HPV infection. Our study included 1000 women from Sonora, Mexico, who participated in cervical cancer screening campaigns and who underwent a Pap smear and HPV DNA test. The results showed that the overall prevalence of HPV was 27.2%, 18.5% with single, and 8.7% multiple infections. The low-risk HPV genotype 6 (8.5%) and oncogenic genotypes 31 (8.1%) and 53 (4.4%) were the most prevalent in the study population. The number of lifetime sexual partners, previous STIs, and age at first intercourse was significantly associated with HPV infection (P ≤ 0.05). Smoking (OR = 1.5609; 95% IC 1.062–2.292) and more than three lifetime sexual partners (OR = 1.609; 95% IC = 1.124–2.303) represented risk factors for HPV infection. Cytological abnormalities were found in 3.4% of the HPV-positive samples. CIN 1–3 occurred in 0.6% of high-risk HPV cases. In general, the prevalence of the HPV genotypes is high in Mexican women with normal cytological findings. This issue highlights the importance of HPV research in seemingly healthy women and could help guide screening strategies for cervical cancer prevention in Mexico.
Impact statement
We are submitting data regarding the prevalence and type distribution of the HPV infection and the risk factors associated with it, which may provide a valuable reference to reinforce screening strategies, and to maintain HPV genotype surveillance in Mexico. We discuss the overall prevalence of HPV infection as detected in normal cytological samples stratified by age, different types of infection, and oncogenic capacity. One of the most important findings was that common HPV genotypes detected in healthy women were the genotype numbers: 6, 31, 16, and 56, likewise, smoking and having a history of more than three sexual partners over their lifetime, represented the main risk factors in this study. Furthermore, we found a low frequency of cytological abnormalities and CIN 1–3 in women with HR-HPV.
BruniLDiazMCastellsagueXFerrerEBoschFXde SanjoseS.Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis2010;
202:1789–99
2.
FerlayJSoerjomataramIDikshitREserSMathersCRebeloMParkinDMFormanDBrayF.Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer2015;
136:E359–86
3.
Van DoorslaerKLiZXirasagarSMaesPKaminskyDLiouDSunQKaurRHuyenYMcBrideAA.The papillomavirus episteme: a major update to the papillomavirus sequence database. Nucleic Acids Res2017;
45:D499–D506
4.
DoorbarJQuintWBanksLBravoIGStolerMBrokerTRStanleyMA.The biology and life-cycle of human papillomaviruses. Vaccine2012;
30(Suppl 5):F55–70
5.
EgawaNEgawaKGriffinHDoorbarJ.Human papillomaviruses; epithelial tropisms, and the development of neoplasia. Viruses2015;
7:3863–90
6.
DoorbarJEgawaNGriffinHKranjecCMurakamiI.Human papillomavirus molecular biology and disease association. Rev Med Virol2015;
25(Suppl 1):2–23
7.
de VilliersEMFauquetCBrokerTRBernardHUZur HausenH.Classification of papillomaviruses. Virology2004;
324:17–27
8.
SchiffmanMCliffordGBuonaguroFM.Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline. Infect Agent Cancer2009;
4:8
9.
WalboomersJMJacobsMVManosMMBoschFXKummerJAShahKVSnijdersPJPetoJMeijerCJMunozN.Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol1999;
189:12–9
10.
BoschFXMunozN.The viral etiology of cervical cancer. Virus Res2002;
89:183–90
11.
BoschFXLorinczAMunozNMeijerCJShahKV.The causal relation between human papillomavirus and cervical cancer. J Clin Pathol2002;
55:244–65
12.
MirabelloLYeagerMCullenMBolandJFChenZWentzensenNZhangXYuKYangQMitchellJRobersonDBassSXiaoYBurdettLRaine-BennettTLoreyTCastlePEBurkRDSchiffmanM.HPV16 sublineage associations with histology-specific cancer risk using HPV whole-genome sequences in 3200 women. J Natl Cancer Inst2016;
108:djw100
13.
SchiffmanMRodriguezACChenZWacholderSHerreroRHildesheimADesalleRBefanoBYuKSafaeianMShermanMEMoralesJGuillenDAlfaroMHutchinsonMSolomonDCastlePEBurkRD.A population-based prospective study of carcinogenic human papillomavirus variant lineages, viral persistence, and cervical neoplasia. Cancer Res2010;
70:3159–69
14.
Arias-PulidoHPeytonCLTorrez-MartinezNAndersonDNWheelerCM.Human papillomavirus type 18 variant lineages in United States populations characterized by sequence analysis of LCR-E6, E2, and L1 regions. Virology2005;
338:22–34
15.
de MartelCFerlayJFranceschiSVignatJBrayFFormanDPlummerM.Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol2012;
13:607–15
PettMColemanN.Integration of high-risk human papillomavirus: a key event in cervical carcinogenesis?J Pathol2007;
212:356–67
18.
WilliamsVMFilippovaMSotoUDuerksen-HughesPJ.HPV-DNA integration and carcinogenesis: putative roles for inflammation and oxidative stress. Future Virol2011;
6:45–57
19.
FranceschiS.The IARC commitment to cancer prevention: the example of papillomavirus and cervical cancer. Recent Results Cancer Res2005;
166:277–97
20.
RizzoAEFeldmanS.Update on primary HPV screening for cervical cancer prevention. Curr Probl Cancer2018;
42:507–20
21.
PapanicolaouGNTrautHF.The diagnostic value of vaginal smears in carcinoma of the uterus. 1941. Arch Pathol Lab Med1997;
121:211–24
22.
FranceschiSHerreroRCliffordGMSnijdersPJArslanAAnhPTBoschFXFerreccioCHieuNTLazcano-PonceEMatosEMolanoMQiaoYLRajkumarRRoncoGde SanjoseSShinHRSukvirachSThomasJOMeijerCJMunozN.Variations in the age-specific curves of human papillomavirus prevalence in women worldwide. Int J Cancer2006;
119:2677–84
23.
FormanDde MartelCLaceyCJSoerjomataramILortet-TieulentJBruniLVignatJFerlayJBrayFPlummerMFranceschiS.Global burden of human papillomavirus and related diseases. Vaccine2012;
30(Suppl 5):F12–23
24.
Van DoorslaerKTanQXirasagarSBandaruSGopalanVMohamoudYHuyenYMcBrideAA.The papillomavirus episteme: a Central resource for papillomavirus sequence data and analysis. Nucleic Acids Res2013;
41:D571–8
25.
GrahamSV.The human papillomavirus replication cycle, and its links to cancer progression: a comprehensive review. Clin Sci2017;
131:2201–21
26.
RaffABWoodhamAWRaffLMSkeateJGYanLDa SilvaDMSchelhaasMKastWM.The evolving field of human papillomavirus receptor research: a review of binding and entry. J Virol2013;
87:6062–72
27.
CriccaMMarascoEAlessandriniFFazioCProssomaritiASaviniCVenturoliSChiecoPCarolis BonafeDSReMGaragnaniMCMantovaniP.V. High-throughput genotyping of high-risk human papillomavirus by MALDI-TOF mass spectrometry-based method. New Microbiol2015;
38:211–23
28.
KriegsmannMWandernothPLisenkoKCasadonteRLonguespeeRArensNKriegsmannJ.Detection of HPV subtypes by mass spectrometry in FFPE tissue specimens: a reliable tool for routine diagnostics. J Clin Pathol2017;
70:417–23
29.
BasuPChandnaPBamezaiRNSiddiqiMSaranathDLearARatnamS.MassARRAY spectrometry is more sensitive than PreTect HPV-Proofer and consensus PCR for type-specific detection of high-risk oncogenic human papillomavirus genotypes in cervical cancer. J Clin Microbiol2011;
49:3537–44
30.
Soderlund-StrandADillnerJCarlsonJ.High-throughput genotyping of oncogenic human papilloma viruses with MALDI-TOF mass spectrometry. Clin Chem2008;
54:86–92
31.
Orozco-ColinACarrillo-GarciaAMendez-TenorioAPonce-de-LeonSMoharAMaldonado-RodriguezRGuerra-AriasRFlores-GilOSotelo-RegilRLizanoM.Geographical variation in human papillomavirus prevalence in Mexican women with normal cytology. Int J Infect Dis2010;
14:e1082–7
32.
Illades-AguiarB, A-RLdelCAntonio-VejarVZamudio-LopezNSales-LinaresNFlores-AlfaroEFernandez-TilapaGVences-VelazquezAMunoz-ValleJFLeyva-VazquezMA.Prevalence and distribution of human papillomavirus types in cervical cancer, squamous intraepithelial lesions, and with no intraepithelial lesions in women from Southern Mexico. Gynecol Oncol2010;
117:291–6
33.
Velazquez-MarquezNParedes-TelloMAPerez-TerronHSantos-LopezGReyes-LeyvaJVallejo-RuizV.Prevalence of human papillomavirus genotypes in women from a rural region of Puebla, Mexico. Int J Infect Dis2009;
13:690–5
34.
Illades-AguiarBCortes-MalagonEMAntonio-VejarVZamudio-LopezN, A-RLdelCFernandez-TilapaGHernandez-SoteloDTeran-PorcayoMAFlores-AlfaroELeyva-VazquezMA.Cervical carcinoma in Southern Mexico: human papillomavirus and cofactors. Cancer Detect Prev2009;
32:300–7
35.
Sanchez-AnguianoLFAlvarado-EsquivelCReyes-RomeroMACarreraRM.Human papillomavirus infections in women seeking cervical papanicolaou cytology of Durango, Mexico: prevalence and genotypes. BMC Infect Dis2006;
6:27
36.
Torroella-KouriMMorsbergerSCarrilloAMoharAMenesesAIbarraMDanielRWGhaffariAMSolorzaGShahKV.HPV prevalence among Mexican women with neoplastic and normal cervixes. Gynecol Oncol1998;
70:115–20
37.
Lazcano-PonceEHerreroRMunozNCruzAShahKVAlonsoPHernandezPSalmeronJHernandezM.Epidemiology of HPV infection among Mexican women with normal cervical cytology. Int J Cancer2001;
91:412–20
38.
SalcedoMPina-SanchezPVallejo-RuizVMonroy-GarciaAAguilar-LemarroyACortes-GutierrezEISantos-LopezGMontoya-FuentesHGrijalvaRMadrid-MarinaVApresa-GarciaTHernandezDMJave-SuarezLFRomeroPPootASalgadoERamos-GonzalezPGonzalez-HernandezRCantonJCJimenez-ArandaLParra-MelquiadezMPaniaguaLMendozaMArreolaHVillegasVTorres-PovedaKBahena-RomanMGonzalez-YebraBTaniguchiKRodeaCMantilla-MoralesA.Human papillomavirus genotypes among females in Mexico: a study from the Mexican Institute for Social Security. Asian Pac J Cancer Prev2014;
15:10061–6
39.
Torres-IbarraLCuzickJLorinczATSpiegelmanDLazcano-PonceEFrancoELMoscickiABMahmudSMWheelerCMRivera-ParedezBHernández-LópezRLeón-MaldonadoLSalmerónJ, FRIDA Study Group.Comparison of HPV-16 and HPV-18 genotyping and cytological testing as triage testing within human papillomavirus-based screening in Mexico. JAMA Netw Open2019;
2:e1915781
40.
Navarro-VidalEHernandez-RosasFReyMFlores-PeredoL.Prevalence of human papillomavirus genotypes in women from cozumel,Mexico. Asian Pac J Cancer Prev2018;
19:2417–22
41.
CiapponiABardachAGlujovskyDGibbonsLPicconiMA.Type-specific HPV prevalence in cervical cancer and high-grade lesions in Latin America and the Caribbean: systematic review and meta-analysis. PLoS One2011;
6:e25493
42.
MunozNBoschFXde SanjoseSHerreroRCastellsagueXShahKVSnijdersPJMeijerCJ.International agency for research on cancer multicenter cervical cancer study G. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med2003;
348:518–27
43.
ChanPKHoWCWongMCChangARChorJSYuMY.Epidemiologic risk profile of infection with different groups of human papillomaviruses. J Med Virol2009;
81:1635–44
44.
LiuZCLiuWDLiuYHYeXHChenSD.Multiple sexual partners as a potential independent risk factor for cervical cancer: a meta-analysis of epidemiological studies. Asian Pac J Cancer Prev2015;
16:3893–900
45.
RombaldiRLSerafiniEPVillaLLVanniACBareaFFrassiniRXavierMPaesiS.Infection with human papillomaviruses of sexual partners of women having cervical intraepithelial neoplasia. Braz J Med Biol Res2006;
39:177–87
46.
CastlePEJeronimoJSchiffmanMHerreroRRodriguezACBrattiMCHildesheimAWacholderSLongLRNeveLPfeifferRBurkRD.Age-related changes of the cervix influence human papillomavirus type distribution. Cancer Res2006;
66:1218–24
47.
KjellbergLHallmansGAhrenAMJohanssonRBergmanFWadellGAngstromTDillnerJ.Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection. Br J Cancer2000;
82:1332–8
48.
PanattoDAmiciziaDBianchiSFratiERZottiCMLaiPLDomnichAColzaniDGaspariniRTanziE.Chlamydia trachomatis prevalence and chlamydial/HPV co-infection among HPV-unvaccinated young Italian females with normal cytology. Hum Vaccin Immunother2015;
11:270–6
49.
Cigarette smoking linked to increased human papillomavirus DNA load. CA Cancer J Clin2010;
60:137–8
50.
WileyDJWiesmeierEMasongsongEGylysKHKoutskyLAFerrisDGBarrEYu RaoJProof Of Principle Study InvestigativeG.Smokers at higher risk for undetected antibody for oncogenic human papillomavirus type 16 infection. Cancer Epidemiol Biomarkers Prev2006;
15:915–20
51.
VaccarellaSHerreroRSnijdersPJDaiMThomasJOHieuNTFerreccioCMatosEPossoHde SanjoseSShinHRSukvirachSLazcano-PonceEMunozNMeijerCJFranceschiSGroupI.Smoking and human papillomavirus infection: pooled analysis of the international agency for research on cancer HPV prevalence surveys. Int J Epidemiol2008;
37:536–46
52.
SyrjanenKShabalovaIPetrovichevNKozachenkoVZakharovaTPajanidiJPodistovJChemerisGSozaevaLLipovaETsidaevaIIvanchenkoOPshepurkoAZakharenkoSNerovjnaRKljukinaLErokhinaOBranovskajaMNikitinaMGrunbergaVGrunbergAJuschenkoASantopietroRCintorinoMTosiP, SS.Smoking is an independent risk factor for oncogenic human papillomavirus (HPV) infections but not for high-grade CIN. Eur J Epidemiol2007;
22:723–35
53.
KoshiolJSchroederJJamiesonDJMarshallSWDuerrAHeiligCMShahKVKleinRSCu-UvinSSchumanPCelentanoDSmithJS.Smoking and time to clearance of human papillomavirus infection in HIV-seropositive and HIV-seronegative women. Am J Epidemiol2006;
164:176–83
KjaerSKvan den BruleAJBockJEPollPAEngholmGShermanMEWalboomersJMMeijerCJ.Determinants for genital human papillomavirus (HPV) infection in 1000 randomly chosen young Danish women with normal pap smear: are there different risk profiles for oncogenic and nononcogenic HPV types?Cancer Epidemiol Biomarkers Prev1997;
6:799–805
56.
YlitaloNSorensenPJosefssonAFrischMSparenPPontenJGyllenstenUMelbyeMAdamiHO.Smoking and oral contraceptives as risk factors for cervical carcinoma in situ. Int J Cancer1999;
81:357–65
57.
KurmanRJHensonDEHerbstALNollerKLSchiffmanMH.Interim guidelines for management of abnormal cervical cytology. The 1992 national cancer institute workshop. JAMA1994;
271:1866–9
58.
TamarelleJThiebautACMde BarbeyracBBebearCRavelJDelarocque-AstagneauE.The vaginal microbiota and its association with human papillomavirus, Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasma genitalium infections: a systematic review and Meta-analysis. Clin Microbiol Infect2019;
25:35–47
59.
CuzickJClavelCPetryKUMeijerCJHoyerHRatnamSSzarewskiABirembautPKulasingamSSasieniPIftnerT.Overview of the European and North American studies on HPV testing in primary cervical cancer screening. Int J Cancer2006;
119:1095–101
60.
SmelovVElfstromKMJohanssonALEklundCNauclerPArnheim-DahlstromLDillnerJ.Long-term HPV type-specific risks of high-grade cervical intraepithelial lesions: a 14-year follow-up of a randomized primary HPV screening trial. Int J Cancer2015;
136:1171–80
61.
CuzickJArbynMSankaranarayananRTsuVRoncoGMayrandMHDillnerJMeijerCJ.Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries. Vaccine2008;
26(Suppl 10):K29–41
62.
CastlePESchiffmanMWheelerCMWentzensenNGravittPE.Human papillomavirus genotypes in cervical intraepithelial neoplasia grade 3. Cancer Epidemiol Biomarkers Prev2010;
19:1675–81
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
