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Cancer Detection and Prevention 32 (2009) 300–307

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Cervical carcinoma in Southern Mexico: Human
papillomavirus and cofactors§
Berenice Illades-Aguiar PhDa,*, Enoc-Mariano Cortés-Malagón MSa,
Verónica Antonio-Véjar MSa, Noelio Zamudio-López MSa,
Luz del Carmen Alarcón-Romero PhDa, Gloria Fernández-Tilapa PhDa,
Daniel Hernández-Sotelo MSa, Marco-Antonio Terán-Porcayo MDb,
Eugenia Flores-Alfaro MSa, Marco-Antonio Leyva-Vázquez PhDa
a
Laboratorio de Biomedicina Molecular, Unidad Académica de Ciencias Quı́mico Biológicas,
Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, Mexico
b
Instituto Estatal de Cancerologı́a ‘‘Dr. Arturo Beltrán Ortega’’, Acapulco, Guerrero, Mexico
Accepted 10 September 2008

Abstract

Background: This study was conducted to determine human papillomavirus (HPV) types in women with cervical cancer (CC) and normal
cervical cytology in the Southern region of Mexico, and to know the contribution of HPV types and cofactors in cervical cancer etiology.
Methods: A case–control study was performed in 133 women with CC and 256 controls. HPV detection was done by MY09/11 and GP5+/
GP6+ PCR systems and typing by restriction fragment length polymorphism or DNA sequencing. Results: HPV was found in 100% of CC and
35.5% of controls. The genotype distribution in CC was: HPV 16 (66.8%), 18 (9%), 31 (7.5%), 45 (4.5%), 58 (3.7%), 69 (3%), 52 (1.6%), 6,
11, 33, 56, and 67 (0.8% each). Among controls, HPV 33 followed by HPV 16 were the most frequent. Cervical cancer was associated with
HPV 16 (OR = 573.5), HPV 18 (OR = 804.4), and undetermined risk HPV (types 67 and 69) (OR = 434.3). Age at first intercourse <16 years
(OR = 9.6) and 3 births (OR = 16) were significant risk factors for CC. Conclusions: HPV 16, by far, is the most frequent type in CC, HPV
16 and 18 are responsible for 75.8% of the CC cases and high-risk HPV for 94.7%, which is useful data to take into account in vaccination
programs. HPV 33 is the most frequent type in controls and high-risk HPV are more common than low-risk HPV.
# 2008 Elsevier Ltd. All rights reserved.

Keywords: Human papillomavirus epidemiology in Mexico; Human papillomavirus genotypes in Mexico; Human papillomavirus and cervical cancer;
Cervical cancer in Mexico; Cervical cancer risk; Cervical cancer in Latin America; Cervical cancer co-factors; Human papillomavirus in normal cervix; HPV
typing; HPV PCR detection

1. Introduction 493,000 new cases and 274,000 deaths in 2002 [1]. More
than eighty percent of new cases are currently diagnosed in
Cancer of the cervix uteri is the second most important developing countries [1], where there is a high incidence of
cancer among women worldwide with an estimated the disease because there are severe limitations in
screening programs as well as treatment facilities [2]. In
§
Sources of support: This work was supported by Grants S-20 and Latin America, a high incidence and mortality were
97SIBEJ-02-016 from the Sistema de Investigación Benito Juárez-CON- registered for cervical cancer (CC); by the year 2000, some
ACYT, México. 76,000 new cervical cancer cases and almost 30,000 deaths
* Corresponding author. Tel.: +52 747 4710901; fax: +52 747 4710901.
E-mail addresses: ibereni@yahoo.com.mx, ibereni@hotmail.com
were estimated for the whole region, which represent 16%
(B. Illades-Aguiar). and 13% of the world burden, respectively. From Latin

0361-090X/$ – see front matter # 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.cdp.2008.09.001

on the in Acapulco. For HPV 2a. has the lowest mortality rate histological confirmation of invasive cervical cancer and the lowest risk of death from cervical cancer. The cases were 133 contrary. Guerrero. The controls were cancer mortality rate was 11 deaths per 100. 34. 3. there have been relatively few case–control and stored at 20 8C until analysis. from for human beings and have been classified as high-risk or which good quality DNA was confirmed to include them in oncogenic types.5%) highest rates of non-coverage by social security health and adeno/adenosquamous carcinoma (ADC/ADSC) in 14 care services (47. 84. and to describe the contribution of DNA was extracted according to the standard SDS– different HPV types and cofactors in cervical cancer proteinase K–phenol–chloroform method [20].5% sodium dodecyl of HPV types in cervical cancer in Southern Mexico. 31. Inclusion criteria for case subjects were that they had where Mexico City is located. 87. 61. 71. Ayre spatula and endocervix with a cytobrush. reproductive history. Specimen collection reclassified as a subtype of HPV 44 and is considered as low-risk HPV type [11].000 women) and fifth in mortality (ASR 17. 67. smoking that HPV 66 as well as HPV 26.7%). consider that it is arbitrary to the study. Mexico. 28. and to not have gone through cervical in 2005 concluded that human papillomavirus types 16. 7. while the diagnosis. This study was approved by the ethical types. HPV 6. 11. making sure and 45 account for about 80% of invasive cervical cancer that tissue from the transformation zone was taken. Mexico. 81. 85. 18. So far. 74. Limited with cervical scrapes were placed in lysis buffer (10 mM information is available on the prevalence and distribution Tris pH 8. committee of the Cancer Institute of the State of Guerrero. and were removed after taking out cervical material addition to this. 44. 51. Squamous located in the Southern region. were used for cytomorphological examination using Geographical variation in HPV type distribution is known conventional Papanicolaou. 33. 52. / Cancer Detection and Prevention 32 (2009) 300–307 301 American countries. 53. For HPV detection.000 2. 72. 10. Participants answered a standardized question- classify HPV 66 as carcinogenic and they therefore propose naire on sexual behavior. 56. 86. Material and methods incidence (age standardized rates – ASR – 40. 43. 55. cervical HPV 16 is the most prevalent type found in women with scrapes were collected by sampling the ectocervix with an cervical cancer worldwide and together with HPV 18. and one of the states with the (10. 32. regions of the country. samples were tested by the MY09/11 PCR protocol . had not received any treatment. Deaths due to cervical cancer State of Guerrero. HPV 55 was 2.0 and 0. 13. a regional concentration Hospital located did not decrease during the 1990–2000 period.76% yearly average increase. The controls provide a cervical 31. 29. buffered saline (PBS). In sulfate). 68. For cytological analysis and HPV detection. 62. there was a 0. The IARC Monograph Working Group [9] any kind of cancer. cervical cancer is the most common type of The study was carried out in the Cancer Institute of the cancer among women [4]. B.5 per 100. 90. nearly 100 HPV have been described [8] and expected age distribution of the case subjects and had to more than 50 different HPV types primarily infect the anal fulfill the following inclusion criteria: negative diagnosis of and genital tracts. which is cases group. 59 and 66 are carcinogenic scrape containing exfoliated cells from the cervix.5%). HPV detection and typing women with cervical cancer and normal cervical cytology from Southern Mexico. Study population women [3]. 73 and 82 should be habits. 58. Of the highest mortality risk. 69. 39. 77. 57. In Mexico. and that DNA Southern region has the highest mortality rate and the extracted from the biopsy samples was good quality.1 per 100. Illades-Aguiar et al. 45.1. was undertaken to establish which HPV types are circulating in 2. The Central region of Mexico. Mexican women with residence in Guerrero State. 27. 83. The State of Guerrero. cytobrushes to occur in different regions of the world. 40. This study in the State of Guerrero. 70. considered as probably carcinogenic [10]. with Cervical cancer mortality shows heterogeneity in different invasive cervical cancer recruited between 1997 and 2003. and socioeconomic background. Mexico is seventh place in relative 2. mentioned above for cytological screening with cytologi- Certain types of human papillomavirus (HPV) are the cally normal cervical epithelium according to the Bethesda central and necessary cause of cervical cancer worldwide System [19]. 20 mM EDTA pH 8. 30.0. according to the highest cervical cancer rates with the highest mortality classification system of the International Federation of risk for this disease [5].000 women in 256 gynecological patients who attended the hospital 2005 [6]. 35.2. 89 are classified as low-risk control women. and stored at 70 8C until analysis. 91 the risk of cervical cancer is undetermined [10]. conization or hysterectomy. is one of the states with the cell carcinoma (SCC) was diagnosed in 119 cases (89. Control women were selected to match the [7]. 54. Smears collected from around the world [12]. The State of Guerrero cervical Gynecology and Obstetrics (FIGO) [18]. by histological diagnosis. Muñoz et al. DNA etiology.3. Informed consent was obtained from both cases and 42. no exfoliated cells were obtained. A tumor biopsy studies about invasive cervical carcinoma performed in specimen was also taken and was eluted in phosphate- Mexico [13–17].

0.5) and having 3 or more births Integrity of DNA specimens was verified by amplifica. Briefly.22].26] (see: Supplementary Data). age at menarche and smoking. human DNA an apparent association with the risk of developing cervical without HPV DNA and water were used as negative cancer. Statistical analysis Multiple infection was not found in either control or cases (Table 2) (see: Supplementary Data). Of performed to identify more than 40 genital HPV types the women that participated in this study. after adjusting for HPV infection. Table 1 summarizes the main sexual history and GeneAmp PCR System 2400 (Applied Biosystems.6%).302 B. Illades-Aguiar et al. The consensus primers MY09 and MY11 target a 119 (89.2. models for different risk factors.3%).5%) were SCC and 14 (10. 3. of sexual partners. HinfI. performed using STATA software version 9. odds ratios (ORs) and (a-9: HPV 31. CA) with the following steps: an initial step 10 min and control status and the association of these characteristics denaturation at 95 8C. Table 3 summarizes the association of cervical cancer with HPV genotype infection A total of 133 case patients with cervical cancer and 256 using five models and various adjustments. Statistical analysis was The remainder 5. 45 (5. and 69) were also detected.6%). and 6% in women 34 years old or Biosystems. and a-10 (HPV 6 and 11) (Table 2). Analysis of the HPV type-specific were negative or the HPV could not be genotyped by distribution among cases and control women showed that RFLP’s. number controls. The presence of HPV was associated with SCC (OR.2% did not say if they smoked or not. 58 (1. Typing of HPVof randomly selected samples that were provide the number of sexual partners they have had and positive for HPV 33 and HPV 16 was carried out by type. followed by 40 cycles of 95 8C for with cervical carcinoma after various adjustments.2%). however. 3. CA). Fifty-three percent of the cervical each primer.1%).5. In the 1 min. (7.2. CI. HPV types were classified as high-risk versus low.8 mM of controls 50.3%). CaSki and for age.5%) and all cases of SSC and ADC/ADSC were positive When samples analyzed with MY09/11 PCR protocol for HPV DNA.5%) followed by HPV types 18 (9.2). specific PCR with primers designed for the E6 region of Among the 256 control women. 72 8C for 1 min.8% did not [24]. Foster City. 95% CI.7%) was the most frequent type followed using Big Dye Terminator Chemistry Version 3 Cycle by HPV types 18 (7. classification [10]. and a final fully adjusted model.5 ( p = 0. Applied Biosystems. start of sexual activity before age 16 extension at 72 8C for 10 min. Two LR-HPV types (HPV after the purification of PCR products using 75% 6 and 11) and two undetermined risk HPV types (HPV 67 isopropanol and columns (Centri-Sep Spin Columns. 52.5% of cervical cancer. The reaction The average age of the cases was 52. 58 8C for 1 min. specimens from 91 these viral types [25. the For HPV typing. 95% with restriction enzymes BamHI. types and only 11 (4. PstI. 150 mM of each cancer cases occurred in women 50 years old or older.1%). Applied Biosystems. and 58 (4. In the non-adjusted model PC04 and GH20 primers [23].5–+1) (data not shown). In women with ADC/ADSC. 3–84) showed statistically significant tion of a 268-bp region of the human b-globin gene using associations with cervical cancer. Carlsbad. (OR = 9. conserved 450-pb region of the HPV L1 gene. CA).5–26. / Cancer Detection and Prevention 32 (2009) 300–307 [21. Of the cases.1. Results 95% CI. 0. 41% dNTP and 1. 5 samples with HPV 33 and 14 with HPV 16. Foster City.4% cases had a-5 (HPV 69). 31 (7. Foster City. with any HPV type was associated with a 279-fold increase . 6. To estimate the relative risk of cervical cancer associated HPV 16 phylogenetically related types found in this study with HPV types and other risk factors.5%) were ADC/ADSC. 27. they corresponded to the results obtained by MY-RFLPs. Foster City. 76 (29. 31 products were subjected to sequencing analysis. (35. 95% CI. HPV infection control subjects were included in this study. (11. 2 mM MgCl2. amplified PCR products were digested association was found to be not significant (OR = 1. All the sequences It is important to note that in the control group HPV type 33 available for the HPV types were recovered from the NCBI was the most recurrent (13. a-6 (HPV 56). 216.2 years and of the mixtures (50 ml) contained 1 mg of target DNA.25 U of Ampli Taq GoldTM (Applied in women 35–49 years old. type-specific PCR. CA). the presence of HPV DNA was assessed using the the most common HPV type in women with SCC was HPV general GP5+/6+ PCR system [27]. age at menarche and smoking habits.3–4.4% of 95% confidence intervals (CIs) were calculated by using cervical cancer cases and HPV 18 phylogenetically related logistic regression in non-adjusted models and adjusted types (a-7: HPV 45) were present in 4. 67) were present in 14. CA) and restriction found not to be associated with cervical cancer included fragment length polymorphism (RFLP) analysis were number of sexual partners.7%) followed by HPV types 16 site [28]. CA) in an control subjects. HPV 16 plasmid. Other characteristics that were examined and RsaI and Sau3AI (Invitrogen. 2.3%) where infected with low-risk types. Foster reproductive factors characteristics of study subjects by case City. 58. DdeI.1%).1%) and 69 (7.6%) were infected with high-risk automated sequencer (310 ABI PRISM Genetic Analyzer. 58.6. PCR buffer 1X. HaeIII. 95% CI. 33.4. 56–+1) and with ADC/ADSC (OR.6). menopause in women younger than 45 years showed HeLa cells were used as positive controls. (OR = 16. When we analyzed by risk accordingly to Muñoz et al. In Sequencing Kit (Applied Biosystems. 64. DNA was amplified in a younger.6%) and 61 (1. PCR GP5+/GP6+ type 16 (65. these were sequenced HPV type 16 (78.

1) 34 (13.4–14) 3 and more 114 (85.8–19.3) 8.1–+1).0 1.5–2.1%).3) 51 (19. HPV 16 is by far the most risks were associated with HPV 18 (OR= 804. HPV genotype distribution risk HPV were associated with cervical cancer (OR = 434.1.6 (0.0 (0.75) 6 (2. 31.2–6.7 (1.4) 1.4. Mexico.6) 0.7 (0. types (OR = 312.6) 1.8) 8. b OR adjusted by sexual partners.0) Did not answer 9 (6.0 1. The 71.5) <45 20 (15.8 (4.9) 1. Variable Cases (n = 133) Controls (n = 256) ORa (95% CI) ORb (95% CI) ORc (95% CI) n (%) n (%) Age at first sexual intercourse (years) >20 17 (12.7) 16 (3. low-risk HPV. a Odd ratio non-adjusted.1–8. Discussion worldwide HPV 16 was identified in 55.7) 172 (67.5) Did not answer 5 (3.7) Did not remember 36 (27.0 (0.5) 1.6) 2.7–39% in ADC/ . HPV types identified in SCC.2–3.9) 94 (36.0–84) Did not answer 2 (1.8) 4 (1.0 Yes 7 (5.2–1. 22. high-risk HPV and undetermined risk HPV).4) 0.1) Age at menopause (years) 50 or more 16 (12.5 (0.0 1.5–+1) was higher than that 33. in the risk of cervical cancer.9) 48 (18.5 (0.0 1.1) 128 (50.2–1.6–1. CI = confidence interval.3 (0.5%).3) 13 (5.6–6. 56. 27.8) 166 (64.0) <16 52 (39. 45.2 (0.4–16.1% of the cervical cancer cases [17].1–1.0 1.3% of SCC [30] and 37.2) 2.6 (0.1) 1. smoking (except for the evaluated factor).8 (0.6 (1.6–3. is present in 12.9) Smoking No 81 (60. HPV 16 was found more often in ADC/ADSC (78.7% of the cervical cancer Analysis of the risk of developing cervical cancer with cases.3% of ADC [30].2–1. 95% CI.9) 1.9 (0.6) 0.0) 2.2) 10.3–1.6) No menopause 36 (27.0) 2. 31.0) 0.0 1–2 15 (11. similar to that found in North Africa and South America where HPV 16 was found in 72% of the ADC cases [29].8) 149(58.2–1.9) 4.9) 1. in ADC/ADSC they were HPV 16 and 18. 95% CI.0 1. Surprisingly.2 (0. 10.0 1.1) 1. 69. which disagrees with was confirmed in 100% of cervical cancer cases (SCC and other studies in which it is found that throughout the world it ADC/ADSC) and in 35.7–1.3) Parity None 2 (1.4) 121 (47.0) 4 and more 5 (3.0 2–3 30 (22.9–+1).6 (0.1–+1) and HPV 16 (OR = 573. HR-HPVs were present in 94.5 (4.0) 0.6–46.9 (1. the presence of HPV DNA (9.5) 1.9) Did not answer 45 (33.3) 2.6 (0.0) 0. 69.1. and in a study from Mexico City it was This study provides information on the risk factors for found in 45.2) OR = odds ratio.5) 0 Sexual partners 1 69 (51.5 (0.5.1) 0.0 1.5 (2. similar to that found in other worldwide studies [7] HPV 16.4 (0.3 (1. among those infected with HPV 16 related types (OR = 86.5–26.0 10–13 60 (45. In this study.8) Age at menarche (years) 14 and more 64 (48.6–2.5) 38 (14.7%) than in SCC (65.8) 9.8) 8 (3. 95% CI.9) 1.2–2.8) 0.0) 26 (10.7) 1.9 (2. c OR adjusted by factors of model c and HPV type by oncongenic risk (HPV negative.4–+1).3%) than in ADC/ADSC (7.2–4. were HPV 16. age at menarche. Illades-Aguiar et al.3. B.0–22.1–18.0 1.0 1.8) 53 (20.0) 1.5–3.2–3.7) 1.0 1.5) 1.0 (0.0 45–49 25 (18.9 (0. 95% CI. however.4) 2.1–5.4) Did not answer 29 (21. 4. common HPV type identified in cervical carcinoma.2.8–56. 11.3–4.0 (0.1) 120 (46.1) 111 (43.1 (0. 74. undetermined 4. 52 and 6.5) 33 (12.5–5.1) 0.1) 15 (5.5 (0.7–3.5 (1. We found cervical cancer and the infection of HPV in the State of that in Southern Mexico.2% of SCC and in 31.5) 12.0 16–20 59 (44. 18.6 (3.0) 51 (19. HPV 18 and related types showed that the highest and in Mexico as well [17]. in order of decreasing The relative risk in women infected with HPV 18 related prevalence. There was variation in HPV-specific prevalence between 95% CI. / Cancer Detection and Prevention 32 (2009) 300–307 303 Table 1 Cervical cancer: associations with sexual history and reproductive factors.3–1.6) 0. HPV 18 was more frequent in SCC Guerrero. different histological cancer types.5% of control women.6) 3.8) 95 (37. 58. 67.3 (0.8) 1.

2 (78–+1) (1)–(5) HPV.0) 0 (0) 71 0 (0) 0 (0) 0 (0) 1 (0.2) LR-HPV 2 (1. 70.4) 67 1 (0.8) 29 (11.2 (33.9–+1) 312.4) Probable HR-PV 0 (0) 0 (0) 0 (0) 3 (1.2) 53 0 (0) 0 (0) 0 (0) 3 (1.4–+1) 522.24]. Models.7) 45 6 (5.4–+1) HPV 16 related typesb(3) 19 42 74. 67 [10. OR. a Undetermined risk HPV: 67.7) 0 (0) 2 (1.4) Undetermined risk-HPV 4 (3.4–+1) 293.7) 76 (29. HR-HPV.0* 1.5–+1) HPV 18 and related types(4) 18 7 424.9 (2.3–+1) HPV 18(3) 12 3 660 (63.8) 0 (0) 1 (0.8–+1) HR-HPV(2) 126 76 273. Table 3 HPV infection and its association with cervical cancer.8) 0 (0) 1 (0.9) 126 (94.1–+1) HPV 18 related typesc(3) 6 4 247. confidence interval.8) 0 (0) 69 3 (2.5–+1) 321 (43. low-risk human papillomavirus.1) 12 (9.1) 11 1 (0. a Muñoz et al.8) 0 (0) 1 (0.8) 0 (0) 1 (0.6 (37.5) Positive 119 (100) 14 (100) 133 (100) 91 (35.9–+1) HPV 16 and related types(4) 108 71 251 (34.7–+1) 804.6–+1) HPV types LR-HPV(2) 2 11 30 (2.3) 1 (7.7) 4 (1.6) 11 (4.5(74.8–+1) 573.8) 0 (0) 58 5 (4.1–+1) Undetermined risk HPVa(2) 5 1 825 (44.1–+1) 597.8) 81 0 (0) 0 (0) 0 (0) 1 (0.24].8) 35 (13. 85 [10.24].5 (23. 33.1–+1) HPV 16(3) 89 29 506. HPV typesa Cervical cancer Controls Squamous cell Adeno/ Total cases carcinoma adenosquamous carcinoma n (%) n (%) n (%) n (%) Total 119 (100) 14 (100) 133 (100) 256 (100) Negative 0 (0) 0 (0) 0 (0) 165 (64.7 (39.5–+1) HPV 16 or HPV 18(5) 101 32 520.304 B.1) 33 1 (0.3 (22.6) 16 78 (65.6) 0 (0) 2 (1. 59.6) 59 0 (0) 0 (0) 0 (0) 1 (0. 45.6) 0 (0) 56 1 (0.2 (27.1) 0 (0) 6 (4. .1) 31 9 (7.0 * Positive (any type) 133 91 241. CI.4 (71.1) 5 (3.4) 1 (7.8) 0 (0) 1 (0. c HPV 18 related types: 39.2) 0 (0) 5 (3.9–+1) 434. human papillomavirus.0) 13 (92.3) 18 11 (9. 52.4 (67.8) 3 (1.4) 61 0 (0) 0 (0) 0 (0) 4 (1.3) 6 1 (0.5) 11 (78. HPV classification [10]. 58.0) 3 (1.5) HR-HPV 113 (95.1) 10 (7.3 (49.6) 1 (7. / Cancer Detection and Prevention 32 (2009) 300–307 Table 2 Distribution of HPV types in cases of cervical cancer and control women with normal cervical cytology. odds ratio. 71 [10.7) 89 (66.1) 4 (3.1 (10. 69. HPV infection Cases (n = 133) Controls (n = 256) ORd (95% CI) ORe (95% CI) HPV(1) Negative 0 165 1.4) 52 2 (1.5) 1 (0. Illades-Aguiar et al.2–+1) 279 (37.7–+1) 86. *reference category for all models.4) HPV.6) 1 (7.8) 1 (0. LR-HPV. high-risk human papillomavirus. human papillomavirus.5) 3 (1. d Odd ratio non-adjusted.6 (9.3 (57.6) 70 0 (0) 0 (0) 0 (0) 2 (0.8 (70.8) 1 (0. b HPV 16 related types: 31. e Odds ratio adjusted for age at first sexual intercourse and parity.5–+1) 34.

followed by HPV 16.8% of cervical cancer cases. The the transitory infections could be present in the calculation heterogeneity of the HPV genotypes distribution in Mexico of the ORs. 9 were HR-HPV. It is interesting to address that undetermined common HPV type. HPV distribution of HPV types in cytologically normal women 18. From those. 56 and 11 is similar to that in cytology is low (0–2. The use of hospital controls. the bivalent vaccine in theory could detection systems increased HPV DNA detection in cervical . 18. 31. In the and GP5+/6+ PCR systems.29. 45. without letting us know if the infection is transitory of In this study multiple infections were not found in cases persistent. Our population is different from others associated with cervical carcinoma. In cases and control studies. the tetravalent HPV 18 in ADC/ADSC is 13.33]. 11.2% [32]. who found 26 types in a being positive. PCR for HPV 33 carried out in 11% of the samples of normal It is important to take into account that HPV status in the cervical cytology with HPV 33 and in the only cervical control group is variable because transient infections could cancer sample with the this viral type. and 81. In this study we found detection of infections with multiple HPV types. [33] in which type of studies. 45 and 58) could the same as reported worldwide [10]. in Asia 8. 53. HPV 58 change in infection status throughout time cannot be was the most frequent type found in LSIL and HSIL. hand.6%. followed by HPV 42. 1 probable tails. has advantages such as The presence of HPV was associated with SCC and with high participation and disadvantages like potential for ADC/ADSC. although in women with Central/South America. Combination of two PCR south of Mexico. in North Africa the frequency of prevent 75. in case of that reported by Muñoz et al.3%. were absent in ADC and were only found in SCC and control The prevalence of infection by HPV in population-based women. The most frequent HPV species associated that HR-HPVs are present in 29. an effective vaccine against 18 was 74. these are 12 types of HPV including types 67 and 69.7%. and strong associations reported by the International Agency for Research on (OR > 18) for HPV 16 related types like in other worldwide Cancer HPV in 2005 [32] showed that HPV 16 was the most studies [10]. This could be due to the methods employed for The geographic distribution and prevalence of HPV types typing (RFLPs or sequencing) which are not suitable for the in cervical cancer varies worldwide. and in evaluated. a single measure cervical cancer cases its frequency was the same as HPV 16 is done that allows us to know the current HPV infection (see: Supplementary Data). 58. LR-HPVs are only present in 4.6% of the controls while with cervical cancer was a-9 HPV followed by a-7 HPV. ten more types were also associated with invasive 31. The fraction of SCC attributable to HPV 16 and unprotected. like in our study.35]. 71.5% of the cases of cervical cancer. and 18 (Gardasil). a basal risk is et al. / Cancer Detection and Prevention 32 (2009) 300–307 305 ADSC [29. 59. [31].8% while that for ADC/ADSC was 85. The prevalence we found for HPV types 16. On the other not reported. Knowledge of geographic distribu. and a tetravalent presence of these HPV types was detected using MY09/11 vaccine against HPV 6. B. [13] did not find HPV 33 in Mexico City and Lazcano- present in both cases and controls. 31. the presence 52 and 6 is similar to that found in Northern Africa and the of multiple infections in women with normal cervical prevalence for types 18. confirmed that our findings were real.2. 70. assuming that an effect of Ponce et al. Type-specific in the development of cervical carcinoma. 61. This partially explains the high frequency of [10.30]. a bivalent HR-HPV. in studies carried out in Mexican women.3%.6% and in South America vaccine could prevent 77. in controls was HPV 33. which could typed by MY-RFLPs. in 4. influence in the estimation of the risk in the cases in which In Mexican women with normal cytology. 12 cervical cancer prevention and screening regarding the HPV types in cervical cancer and 14 HPV types in normal composition of prophylactic vaccines and screening cock. HPV 16. cervical cancer the prevalence is greater [13. worldwide associations (OR > 100) for total HR-HPV. 81.30]. risk HPV (HPV 67 and HPV 69) [10] were very strongly 35. status. and in Europe 5. 16.13. and HPV 18 related types. The vaccine (Cervarix) against HPV 16 and 18. 6. the they found that in women from the State of Yucatan. almost the 5 most common HPV types (16. The most common HPV type this study were associated with HPV 16 and HPV 18. as reported in many studies worldwide selection bias. 58. two HPV vaccines are available. tion of HPV types in cervical cancer has implications for A total of 18 HPV types were detected in this study. it would be difficult to evaluate in this is evident in the study by Gonzalez-Losa et al. Odd ratios linked to HPV types demonstrated very strong In comparison to the south of Mexico. HPV and cervical cancer South America 14. 18. different from less sensitive than hybridization methods and. 56. 31. 5 LR-HPV. in Sub-Saharian Africa it is 25.6% [29]. Because this is not a follow up study.6% 19. Epidemiologically. 45. Illades-Aguiar et al. 11. 58. However. however. On the other hand. so these findings could regarding predominance of HPV 33 in women with normal contribute to determining the association of these HPV types cytology. cervical cytology. which is higher than that of HPV 16. 18.5%). [4] found it in 1% in the State of Morelos. 33 and 45. Three-fourths of invasive cervical cancers in HPV in the controls (35. It is important to mention cervical cancer. studies carried out in different regions of the world is variable. or controls. At present.4%) [4. However. that were previously not be differentiated from persistent infections. and 3 undetermined risk-HPV. In this study LR-HPV prevent 91. leaving 22. these will usually give an uninterpretable multicentric worldwide study in which types 67 and 69 are mix-up of digestion/sequence patterns [34].8%.4% of cases. Torroella-Kouri infection is persistent.

2006. monogamous and in a study that we carried out in Nahuatl Shah KV. a disease of poverty: mortality differences [38]. Rangel-Gómez G. Human papillomavirus is a necessary cause of invasive indigenous women in the year 2000 over 90% reported they cervical cancer worldwide. the high promiscuity of the men could Hybrid Capture II (Digene) assay that detects 13 HR-HPVand explain the high frequency of infection by HPV and shows 5 LR-HPV [36]. it has been assumed and specimen collection. IARC CancerBase invasive cervical cancer are having three or more births and No. would also not detect genotypes 53. cause for cervical cancer [7]. Kummer JA. or the et al. 45:S315–25. We Because infection by HR-HPV is a necessary.salud. at doi:10. Cancer Causes Control facilitating the direct exposure to HPV and possibly other 1997. 2004. polygamy analyzing MY-PCR negative samples with GP5+/6+ PCR is a common practice among men from the State of system. A study shows that 98% of men have had more prevalence found in other studies (83–89% [30]. and Marco Antonio Jiménez for that other factors contribute to modulate the risk of transition histological evaluation of all biopsy material. would not detect genotypes 67 and 69 that why the sexual behavior of the men is an important factor in were found in 3.001. Shah KV. Salud Pública Mex 2003. et al. We found a higher prevalence than the worldwide Guerrero.306 B. The risk factors found by Castañeda-Iñiguez et al. So. women.0. Even though thank technicians of Laboratorio de Biomedicina Molecular there are many studies performed worldwide that analyze for their excellent laboratory assistance. Int J Cancer 2001. Manos MM. et al. Salud Pública Mex 2003.8% of cervical cancer cases in this study. Arturo Beltrán Ortega’’ and Secretarı́a de Salud personnel who helped with this study at the clinic sites. multiparity and a history of many sexual partners. Lazcano- to reach the basal layer and establish a persistent infection Ponce E. [15] in 1998 in women from the State of Zacatecas (Central-Northern Appendix A. Muñoz N. Hormonal changes induced by pregnancy may of cervical cancer in Latin America. in Mexico very few exist. even though the number of the sexual partners the HPV DNA detection.8% using MY09/11 PCR system to 100% by were monogamous (unpublished data). [1] Ferlay J.7% [7]). Cantoral L. start of sexual activity before 16 years of age. References In this study. Supplementary data Mexico) are multiparity.4% of the controls. that the developing cervix. [16] found that the main risk factors for cervical Science Center) for revising the English style of the cancer in women from Mexico City (Central region) are manuscript.1016/j. The cervical cancer screening program in the transformation zone of the exocervix for many years. in this study 60% of the women said that they were [7] Walboomers JM. 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(Mexico City and Veracruz) and Southern region (Morelos) 09. were not risk factors in the development of cervical cancer. It would be important that the composition of screening ‘‘cocktails’’ for HR-HPV and Acknowledgments LR-HPV types be revised as proposed by other studies [37]. Age. women had is not a risk factor in the development of cervical Our findings indicate that the commercially available cancer in this study. Mexico: problems with access and coverage. [3] Arrossi S. early start of sexual activity and the use of oral contraceptives. unfavorable socioeconomic condition. Buiatti E. multiparity. Herrero R. . Tirado-Gómez et al. 71 and 81 which were found in 4. Cruz A. J Pathol 1999. Incidence and mortality cofactors. the risk factors of incidence. It has also been proposed [4] Lazcano-Ponce E. like to thank Dinorah Leyva-Illades (Texas A&M Health Ponce et al. Sankaranarayanan R. Guerrero. and number of sexual partners between urban and rural areas in Mexico. Cofactors for cervical cancer ‘‘Dr.cdp. Cervical cancer. Nájera-Aguilar P. healing cervix are high-risk situations for an HPV infection [5] Palacio-Mejı́a LS.mx/ [Last accessed: 2007 May 8]. lack of access to health services. of Mexico low education levels. In 2005. presence of vaginal infection.2008. in the online version. Available from URL: http://sinais.3. Jacobs MV. Lyon: IARC Press. we found that in the State of Guerrero. of which 60% is infected with HPV and 99. Parkin DM. In 1995. 91:412–20. 8:698–704. Bray F. And we would also these factors. Bosch FX. [17] Supplementary data associated with this article can be found as risk factors in women from the Central region found. also modulate the immune response to HPV and influence 45:S306–14. Alonso P. but not a thank Vı́ctor Hugo Garzón for management of the patients sufficient. as reported in other World populations.

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