¶Membership of the CVT Vaccine Group is provided in the Acknowledgments
JTS and DRL report that they are named inventors on US Government-owned HPV vaccine patents (US 5,437,951; US 5,709,996; US 5,716,620; US 5,744,142; US 5,756,284; US 5,871,998; US 5,985,610; US 7,220,419; and US 7,361,356: “Self-assembling recombinant papillomavirus capsid proteins”) that are licensed to GlaxoSmithKline and Merck and for which the National Cancer Institute receives licensing fees. They are entitled to limited royalties as specified by federal law. The following authors: Wim Quint, Leen-Jan van Doorn and Linda Struijk are employed by the commercial company DDL Diagnostic Laboratory, Rijswijk, The Netherlands. Vaccine was provided for our trial by GlaxoSmithKline Biologicals (GSK), under a Clinical Trials Agreement with the National Cancer Institute. GSK also provided support for aspects of the trial associated with regulatory submission needs of the company under FDA BB-IND 7920. The other authors declare that they have no conflicts of interest. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.
Conceived and designed the experiments: RH AH MS ACR DS JTS DRL SW. Performed the experiments: RH WQ AH PG LS HAK CP MS ACR SJ LJVD. Analyzed the data: RH AH PG HAK MS SW ARK. Contributed reagents/materials/analysis tools: WQ HAK LJVD LS. Wrote the paper: RH AH ARK SW MS DS PG.
Human papillomavirus (HPV) infection, particularly with type 16, causes a growing fraction of oropharyngeal cancers, whose incidence is increasing, mainly in developed countries. In a double-blind controlled trial conducted to investigate vaccine efficacy (VE) of the bivalent HPV 16/18 vaccine against cervical infections and lesions, we estimated VE against prevalent oral HPV infections 4 years after vaccination.
A total of 7,466 women 18–25 years old were randomized (1∶1) to receive the HPV16/18 vaccine or hepatitis A vaccine as control. At the final blinded 4-year study visit, 5,840 participants provided oral specimens (91·9% of eligible women) to evaluate VE against oral infections. Our primary analysis evaluated prevalent oral HPV infection among all vaccinated women with oral and cervical HPV results. Corresponding VE against prevalent cervical HPV16/18 infection was calculated for comparison. Oral prevalence of identifiable mucosal HPV was relatively low (1·7%). Approximately four years after vaccination, there were 15 prevalent HPV16/18 infections in the control group and one in the vaccine group, for an estimated VE of 93·3% (95% CI = 63% to 100%). Corresponding efficacy against prevalent cervical HPV16/18 infection for the same cohort at the same visit was 72·0% (95% CI = 63% to 79%) (p versus oral VE = 0·04). There was no statistically significant protection against other oral HPV infections, though power was limited for these analyses.
HPV prevalence four years after vaccination with the ASO4-adjuvanted HPV16/18 vaccine was much lower among women in the vaccine arm compared to the control arm, suggesting that the vaccine affords strong protection against oral HPV16/18 infection, with potentially important implications for prevention of increasingly common HPV-associated oropharyngeal cancer.
ClinicalTrials.gov, Registry number
A subset of oropharyngeal cancers (OPC) is caused by human papillomavirus (HPV) infection
HPV-positive OPC constitutes a distinct clinico-pathological entity with risk factors different from those for HPV-negative tumors. The incidence of OPC has increased significantly in the US
Randomized trials have provided strong evidence for high efficacy of two virus-like particle (VLP) vaccines: the bivalent HPV16/18 vaccine (
Oral anti-VLP antibodies are detectable in vaccinated subjects albeit at lower levels than those observed systemically
The protocol for this trial and supporting CONSORT checklist are available as supporting information; see
This evaluation of VE against oral HPV infection was conducted in a randomized clinical trial initially designed to evaluate VE against persistent cervical HPV16/18 infection and precancerous lesions
At enrollment, a pelvic examination was performed on sexually experienced women, with collection of exfoliated cervical cells for liquid-based cytology and HPV DNA testing, and blood for HPV16/18 serology. Next, women were randomized in a blinded fashion to the bivalent vaccine or a hepatitis A vaccine (modified
At the final blinded four-year study visit, after a new informed consent, a questionnaire was administered including oral and anal sexual behaviors and an oral specimen was collected by use of a 15-second rinse and 15-second gargle with 15 mL of commercially available alcohol-based mouth wash (Scope®, Procter and Gamble Company, Cincinnati, OH). This method of specimen collection
For HPV DNA testing of oral and cervical specimens, DNA was extracted from each specimen via the MagNAPure LC DNA isolation procedure (Roche Diagnostics); 10 µl of extracted DNA were used for each PCR-reaction. All DNA samples were tested for the presence of HPV DNA by PCR amplification using the HPV SPF10 PCR-DEIA (DNA enzyme immunoassay)-LiPA25 (Line probe assay) version 1 system (Labo Biomedical Products, Rijswijk, The Netherlands). Briefly, this broad-spectrum PCR-based HPV DNA testing system uses SPF10 primers to amplify at least 57 HPV genotypes and the LiPA line detection system to genotype the following carcinogenic and non-carcinogenic HPVs
The first 300 samples collected were tested using multiple volumes (200 µl, 400 µl, 800 µl) for DNA extraction as part of our laboratory optimization phase. The remaining specimens were tested in three batches of approximately the same size using 400 µl for DNA extraction. While we did observe batch-associated differences in the proportion of individuals positive by DEIA who were negative by LiPA (in other words, HPV infections of unknown type), the fraction of specimens positive for HPV16/18 was constant across batches (between 0·2% and 0·4%, excluding pilot), as was the fraction of specimens positive for an oncogenic or non-oncogenic HPV type. Thus, the variation between the batches was only for HPVs of unknown types and not for HPV 16/18 or the other types analyzed. As part of quality control, the final batch was retested with HPV16 or 18 type-specific primers using the same technique as in the primary testing, adding two HPV16 and one HPV18 infections. We decided that the limited potential yield of re-testing the other batches did not justify the extensive testing effort and associated cost. In our primary analysis, all infections detected were included in the analysis. We also conducted a sensitivity analysis excluding specimens positive in the second test (see results).
Serum collected at enrollment was used to determine HPV16 and HPV18 serological status using a VLP-based direct ELISA, for detection of polyclonal antibodies (GlaxoSmithKline Biologicals, Rixensart, Belgium), as described previously
Characteristics of women who accepted or declined the oral collection were compared using a chi-squared test for categorical variables. Among women who accepted, characteristics from the enrollment and four-year post-vaccination visits were compared by study arm. Median follow-up time was calculated and compared by arm using the Kruskal-Wallis test.
Before unblinding the data, we pre-specified our main objective for this analysis, which was an evaluation of VE against prevalent oral HPV16/18 infection approximately four years after the first vaccination among women with both oral and cervical HPV results available. Prevalence of oral HPV16/18 infections was the endpoint evaluated (defined as detection of either HPV16 or HPV18 or both in exfoliated cells from the oral cavity at the four-year study visit). VE against cervical HPV16/18 infections among the same women at the same time point are reported for comparison. Because this value-added component was introduced in response to the mounting evidence that HPV causes some oropharyngeal cancers, there was no pre-vaccination oral specimen obtained which would have allowed for exclusion from the analysis of women with prevalent oral HPV infection (as in a naïve cohort). To compensate, we pre-specified restricted cohorts in which to evaluate VE among women less likely to be exposed to HPV infection at vaccination, based on cervical HPV16/18 DNA or antibodies at enrollment. We also considered evaluating VE among women receiving fewer than three vaccine doses. However, given that only one subject in the vaccine arm had oral HPV16/18 detected 4 years after vaccination, these exploratory analyses became meaningless and were not formally conducted. We present in the results an estimate of VE among women who were HPV negative at the cervix.
Prevalences of oral and cervical HPV infections were expressed as number of infected women per 100 women vaccinated (stratified by vaccine arm). The complement of the ratios of the prevalence for the HPV and control arms constituted our VE estimates. We report asymptotic confidence intervals (95%CI) when cells had more than five events, and exact confidence limits otherwise
Oral and cervical VE estimates were compared using a GEE model
At the time of this analysis, field work was on-going and individual information remained blinded. Thus, analyses were conducted by an external group, Information Management Systems (Rockville, MD), under the direction of the investigators. SAS 9.2 TS2M3 was used for analysis.
Of the 7 466 women randomized, 1 114 did not attend their four-year follow-up visit (
Percentages of women who accepted oral specimen collection were similar in both arms (91·5% vaccine and 92.3% control), although they were lower at one of the study clinics (Nicoya) (
Characteristic | Number of women |
Percent who accepted oral collection | p value |
||
0.59 | |||||
18–19 | 1 859 | 91.6 | . | ||
20–21 | 1 437 | 91.8 | . | ||
22–23 | 1 340 | 92.8 | . | ||
24–25 | 1 204 | 91.8 | . | ||
<0.001 | |||||
Liberia | 1 661 | 92.6 | . | ||
Nicoya | 1 620 | 85.6 | . | ||
Cañas | 1 762 | 97.0 | . | ||
Puntarenas | 797 | 93.7 | . | ||
<0.001 | |||||
0 | 324 | 84.4 | . | ||
1 | 1 489 | 90.5 | . | ||
2–3 | 2 007 | 92.4 | . | ||
4+ | 2 020 | 94.0 | . | ||
<0.001 | |||||
0 | 2 189 | 88.6 | . | ||
1 | 2 105 | 93.3 | . | ||
2+ | 1 516 | 95.3 | . | ||
<0.001 | |||||
Never Had Oral Sex | 2 189 | 88.6 | . | ||
1st tertile (11–19 years) | 1 328 | 95.0 | . | ||
2nd tertile (20–22 years ) | 1 216 | 93.3 | . | ||
3rd tertile (23–32 years ) | 984 | 94.1 | . | ||
<0.001 | |||||
0 | 4 768 | 90.9 | . | ||
1 | 878 | 97.0 | . | ||
2+ | 177 | 97.8 | . | ||
<0.001 | |||||
Never had sex @ Enrollment | 1 137 | 87.1 | . | ||
Negative | 4 184 | 92.8 | . | ||
Positive | 511 | 96.2 | . | ||
0.25 | |||||
Control (Havrix) | 2 928 | 92.3 | . | ||
HPV (Cervarix) | 2 912 | 91.5 | . |
Unknown excluded from calculation.
P value for the comparison of women who did and did not accept oral specimen collections.
Two 17 yr olds are classified in the ‘18–19’ group and one 27 yr old is classified in the ‘24–25’ group.
Among women who agreed to oral specimen collection, there was balance in the HPV and control arms on enrollment characteristics: age at entry, number of clinic visits and self-reported vaginal, oral and anal sex, which were queried at the study visit corresponding to oral specimen collection, and on enrollment history of smoking and cervical HPV 16/18 DNA positivity (
HPV Arm | Control Arm | |||
Characteristic | Number of women |
Percent (Column) | Number of women |
Percent (Column) |
18–19 | 907 | 31.2 | 949 | 32.5 |
20–21 | 739 | 25.4 | 696 | 23.8 |
22–23 | 647 | 22.2 | 693 | 23.7 |
24–25 | 617 | 21.2 | 586 | 20.0 |
1–2 | 11 | 0.4 | 13 | 0.4 |
3–5 | 1.846 | 63.4 | 1.795 | 61.4 |
6–8 | 784 | 26.9 | 813 | 27.8 |
9+ | 269 | 9.2 | 303 | 10.4 |
0 | 168 | 5.8 | 156 | 5.3 |
1 | 715 | 24.6 | 771 | 26.4 |
2–3 | 1.007 | 34.6 | 999 | 34.2 |
4+ | 1.020 | 35.1 | 998 | 34.1 |
0 | 1.070 | 37.0 | 1.117 | 38.4 |
1 | 1.081 | 37.3 | 1.021 | 35.1 |
2+ | 744 | 25.7 | 771 | 26.5 |
Never Had Oral Sex | 1.070 | 37.6 | 1.117 | 39.0 |
1st tertile (11–19) | 660 | 23.2 | 667 | 23.3 |
2nd tertile (20–22) | 610 | 21.4 | 604 | 21.1 |
3rd tertile (23–32) | 505 | 17.8 | 478 | 16.7 |
0 | 2.356 | 81.2 | 2.407 | 82.5 |
1 | 463 | 16.0 | 414 | 14.2 |
2+ | 82 | 2.8 | 95 | 3.3 |
No | 405 | 13.9 | 400 | 13.7 |
Yes | 2.504 | 86.1 | 2.519 | 86.3 |
Liberia | 789 | 27.1 | 871 | 29.8 |
Nicoya | 855 | 29.4 | 764 | 26.1 |
Cañas | 880 | 30.2 | 878 | 30.0 |
Puntarenas | 386 | 13.3 | 411 | 14.1 |
Never had sex @ Enrolment | 551 | 19.0 | 584 | 20.0 |
Negative | 2.117 | 72.8 | 2.063 | 70.7 |
Positive | 239 | 8.2 | 272 | 9.3 |
Unknown excluded from calculation.
Two 17 yr olds are classified in the ‘18–19’ group and one 27 yr old is classified in the ‘24–25’ group.
Chi square p value for difference by arm = 0.02.
Prevalence of detectable oral HPV at the four-year study visit in the control group was 5·4% including identifiable (typeable) and untypeable types, 1·7% for infection with typeable HPV types, 1·3% for infections with oncogenic HPV types and 0·8% for non-oncogenic types. HPV16 was the most common type detected among controls (0·4%). Additional analyses of the uncharacterized oral HPV types detected are on-going. Oral HPV prevalence in the control group was significantly higher among women who were HPV-DNA positive at the cervix (3.5%) compared to those who were negative (1.0%). There was also a statistically significant association with single marital status and increasing numbers of lifetime vaginal sex partners, but there was no clear association with self-reported oral or anal sex
In the full cohort (
Arm | Number of women | Number of women with infection |
Prevalence | 95%CI | Vaccine efficacy | 95%CI |
HPV | 2910 | 1 | 0.0 | 0.0∶0.2 | ||
Control | 2924 | 15 | 0.5 | 0.3∶0.8 | 93.3% | 62.5% to 99.7% |
HPV | 2910 | 1 | 0.0 | 0.0∶0.2 | ||
Control | 2924 | 12 | 0.4 | 0.2∶0.7 | 91.6% | 51.7% to 99.6% |
HPV | 2910 | 0 | 0.0 | 0.0∶0.1 | ||
Control | 2924 | 4 | 0.1 | 0.0∶0.3 | 100% | −12.0% to 100% |
HPV | 2910 | 61 | 2.1 | 1.6∶2.7 | ||
Control | 2924 | 219 | 7.5 | 6.6∶8.5 | 72.0% | 63.0% to 79.1% |
HPV | 2910 | 44 | 1.5 | 1.1∶2.0 | ||
Control | 2924 | 151 | 5.2 | 4.4∶6.0 | 70.7% | 59.3% to 79.3% |
HPV | 2910 | 18 | 0.6 | 0.4∶1.0 | ||
Control | 2924 | 78 | 2.7 | 2.1∶3.3 | 76.8% | 61.9% to 86.5% |
There was one woman with a mixed infection with HPV 16 and 18.
P for arm* site interaction for VE against HPV 16/18 = 0.04.
The subject in the vaccine arm who had an oral HPV infection received only two vaccine doses, as did another 328 in the vaccine arm and 294 in the control arm. In addition, the HPV infection in this particular subject was only detected when her oral specimen was retested as part of quality control. Therefore, in the sensitivity analysis excluding HPV positive results from retested specimens, the VE against oral HPV16/18 infections was 100·0% (zero infection in the vaccine arm, thirteen in the control arm, 95% CI = 74·0% to 100·0%). When excluding women who were HPV 16/18 positive in the cervix at the enrolment visit, VE was 91.7% (95%CI = 52.3% to 99.6%).
There was no evidence of statistically significant protection against HPV31, 51, 52, 56, 39, or 6/11(
Arm | Number of women | Number of women with infection | Prevalence | 95%CI | Vaccine efficacy | 95%CI |
HPV | 2910 | 3 | 0.1 | 0.0∶0.3 | ||
Control | 2924 | 5 | 0.2 | 0.1∶0.4 | 39.7% | −161.0% to 88.1% |
HPV | 2910 | 7 | 0.2 | 0.1∶0.5 | ||
Control | 2924 | 10 | 0.3 | 0.2∶0.6 | 29.7% | −86.9% to 74.7% |
HPV | 2910 | 3 | 0.1 | 0.0∶0.3 | ||
Control | 2924 | 7 | 0.2 | 0.1∶0.5 | 56.9% | −63.9% to 91.0% |
HPV | 2910 | 2 | 0.1 | 0.0∶0.2 | ||
Control | 2924 | 4 | 0.1 | 0.0∶0.3 | 49.8% | −183.2% to 93.6% |
HPV | 2910 | 3 | 0.1 | 0.0∶0.3 | ||
Control | 2924 | 1 | 0.0 | 0.0∶0.2 | −201.4% | −7836.8% to 67.9% |
HPV | 2910 | 4 | 0.1 | 0.0∶0.3 | ||
Control | 2924 | 4 | 0.1 | 0.0∶0.3 | −0.5% | −345.5% to 77.3% |
HPV | 2910 | 19 | 0.7 | 0.4∶1.0 | ||
Control | 2924 | 22 | 0.8 | 0.5∶1.1 | 13.2% | −61.1% to 53.6% |
HPV | 2910 | 20 | 0.7 | 0.4∶1.0 | ||
Control | 2924 | 37 | 1.3 | 0.9∶1.7 | 45.7% | 6.9% to 69.0% |
In this first report evaluating efficacy of an HPV vaccine against oral infection, we observed, as part of a randomized trial of the bivalent vaccine among young women in Costa Rica, a 93·3% reduction of prevalent oral HPV 16/18 infection in the vaccine arm compared to the control arm approximately four years after vaccination.
Because our randomized trial was not specifically designed to evaluate VE against oral HPV infections, we had no baseline information on oral HPV status from study subjects, and we had to rely on HPV prevalence four years after vaccination rather than incidence of new infections. However, the VE estimate from a study restricted to HPV negative women at baseline would likely have been higher than the observed VE of 93%. Vaccination is known to be ineffective against established infections
There is limited knowledge about natural history of oral HPV infection, and the quantitative relationship between one-time detection of HPV in oral exfoliated cells and risk of future OPC is not established. In this context, our study does not constitute direct evidence that the vaccine prevents OPC. However, the high VE against oral HPV16/18 infection supports the possibility that vaccination may reduce risk of HPV-positive OPC, in particular HPV 16, the type most commonly associated with this cancer.
Although surrogate clinical endpoints, such as CIN2 or worse, were used to establish VE against cervical cancer, leading to licensing and mass vaccination programs, that approach is not possible with OPC because it lacks established precursor lesions. Direct evaluation of VE against OPC seems impractical, because given the relative rarity of both infection and OPC and the probably long interval between infection and the occurrence of cancer, such evaluation would require large studies and probably decades to complete. However, additional studies using virologic outcomes may further define the potential utility of HPV vaccines in prevention of these cancers in men and women.
We believe this study constitutes a valid randomized evaluation of VE against prevalent oral infections because the study and laboratory testing were blinded and there was balance by arm on demographic characteristics and risk factors for oral HPV acquisition. More than 90% of women agreed to donate oral specimens and valid HPV results were obtained on all but two of them. Although women who donated an oral specimen had evidence of more sexual activity than the relatively small number of women who did not, the balance by arm on all relevant characteristics is reassuring. In addition, the low prevalence of oral HPV16 infection in our control group (0·4%) was similar to its reported prevalence among healthy subjects in low-risk populations reported in a pooled analysis of 18 studies
VE against prevalent oral HPV16/18 infections was significantly higher than against corresponding cervical HPV16/18 infections (p = 0·04) in the same cohort without excluding enrollment prevalent infections. This is consistent with the possibility that most oral infections were incident, with very few prevalent at enrollment and persisting for four years. Further, oral sex tended to start later than vaginal sex (data not shown), which would also result in a larger fraction of oral infections being acquired after vaccination compared to cervical infections. However, we did not see a clear association of oral HPV infection with oral sex.
Until now, there have been no data on efficacy of any of the HPV vaccines for prevention of oral HPV infection, and this remains the case in men. However, it is likely that the protection we observed among women will also be present in men, as VE of both vaccines has been demonstrated against HPV infections among men and women at all mucosal sites evaluated. Our results suggest that administration of the HPV vaccine will guard against oral infection by the HPV types responsible for the vast majority of HPV-related OPC, and open the possibility of primary prevention of these increasingly common malignancies.
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We would like to extend a special thanks to the women of Guanacaste and Puntarenas, Costa Rica, who gave of themselves in participating in this effort. We also acknowledge the tremendous effort and dedication of the staff in Costa Rica involved in this project, including Bernardo Blanco and his team (census), Ricardo Cerdas and Ana Hernández (blood processing), José Miguel González, Osman López, Johnny Matamoros, Manuel Sánchez, Rafael Thompson and Jorge Umaña (field activity coordinators), Su Yen Araya, Hazel Barquero, Hayleen Campos, Muriel Grijalba, Ana Cristina Monge, Ana Peraza, Diana Robles, María Fernanda Sáenz, Dorita Vargas, and Jessica Vindas (clinic coordinators), Paola Alvarez, Dinia Angulo, Ana Live Arias, Betzaida Barrantes, Marianela Bonilla, Mary José Calvo, Loretto Carvajal, Jessenia Chinchilla, Blanca Cruz, Marianela Herrera, Andrea Interiano, Fabiola Jiménez, Erick Lagos, Viviana Loría, Andrea Messeguer, Rebeca Ocampo, Silvia Padilla, Angie Ramírez, Libia Rivas, Daniela Romero, Byron Romero, Jessenia Ruiz, Daniela Ruiz, Genie Saborío, Sofía Ssoto, Malena Salas, Adriana Torrez, Natalia Ugalde, Ana Cristina Ugalde, Adriana Vallejos, Yesenia Vázquez, Maricela Villegas (clinicians), Marta Alvarado, Ana Cristina Arroyo, Gloriana Barrientos, Diana Díaz, Marlen Jara, Maureen Matarrita, María Ester Molina, Elida Ordóñez, Gina Sánchez, and Zihara Villegas (nurses), Arianne Castrillo and Vivian López (education and outreach effort coordinators), Karla Coronado (appointment coordinator), Ricardo Alfaro (quality control coordinator), Charles Sánchez and Livia Romero (document center coordinators), Cristian Montero (quality assurance, regulatory) and Carlos Avila and Eric Alpízar (IT coordinators). Special recognition is also extended to the staff of Fundación INCIENSA for their administrative support. In the United States we would like to extend our appreciation to the team from Information Management Services (IMS) responsible for the development and maintenance of the data system used in the trial and who serve as the data management center for this effort. We would like to specifically acknowledge the invaluable contributions made by Jean Cyr, Julie Buckland, Laurie Rich, Brian Befano at Information Management Services (IMS) and acknowledge the contributions made by individuals at Westat, Inc., who provided project development and/or monitoring support, including Kerry Grace Morrisey, Kirk Midkiff, Susan Truitt, Sonia Stoszek, Maribel Gomez, and Isabel Trejos. We acknowledge the assistance provided by Carla Chorley, Troy Moore, Kathi Shea, and Heather Siefers in the establishment of a specimen and vaccine repository for our trial and in their continued assistance with the handling and shipment of specimens. From GSK Biologicals, we would like to acknowledge the contributions of Gary Dubin, Anne Schuind, Frank Struyf, Kelechi Lawrence, Darrick Fu, and Bruce Innis for their contribution to discussions regarding trial conduct and Francis Dessy and Catherine Bougelet for HPV-16/18 antibody testing. We would like to thank members of the Data and Safety Monitoring Board charged with protecting the safety and interest of participants in our trial (Steve Self, Chair, Adriana Benavides, Luis Diego Calzada, Ruth Karron, Ritu Nayar, and Nancy Roach) and members of the external Scientific HPV Working Group who have contributed to the success of our efforts over the years (Joanna Cain, Chair, Diane Davey, David DeMets, Francisco Fuster, Ann Gershon, Elizabeth Holly, Silvia Lara, Henriette Raventós, Wasima Rida, Luis Rosero-Bixby, Kristen Suthers, Sarah Thomas and Raphael Viscidi). We thank Annet Westbroek and Yvonne Zomerdijk from DDL for their help in testing the oral specimens, and Sabrina Chen from IMS for help with the analysis.
Cervarix is a registered trade mark of the Glaxo Smith Kline Biologicals group of companies.
Protocol available at
Names and Affiliations of investigators in the Costa Rica Vaccine Trial (CVT) group:
Rolando Herrero (Co-Principal Investigator)
Mario Alfaro (Cytopathologist)
M. Concepción Bratti (co-Investigator)
Bernal Cortés (Specimen and Repository Manager)
Albert Espinoza (Head, Coding and Data Entry)
Yenory Estrada (Pharmacist)
Paula González (co-Investigator)
Diego Guillén (Pathologist)
Silvia E. Jiménez (Co-Investigator, trial coordinator)
Jorge Morales (Colposcopist)
Luis Villegas (Colposcopist)
Lidia Ana Morera (Head Study Nurse)
Carolina Porras (co-Investigator)
Ana Cecilia Rodríguez (co-Investigator)
Allan Hildesheim (co-Principal Investigator & NCI co-Project Officer)
Aimée R. Kreimer (Investigator)
Douglas R. Lowy (HPV Virologist)
Nora Macklin (Trial Coordinator)
Mark Schiffman (Medical Monitor & NCI co-Project Officer)
John T. Schiller (HPV Virologist)
Mark Sherman (QC Pathologist)
Diane Solomon (Medical Monitor & QC Pathologist)
Sholom Wacholder (Statistician)
Enrique Freer (Director, HPV Diagnostics Laboratory)
José Bonilla (Head, HPV Immunology Laboratory)
Alfonso García-Piñeres (Immunologist)
Sandra Silva (Head Microbiologist, HPV Diagnostics Laboratory)
Ivannia Atmella (Microbiologist, Immunology Laboratory)
Margarita Ramírez (Microbiologist, Immunology Laboratory)
Ligia Pinto (Head, HPV Immunology Laboratory)
Troy Kemp (Scientist, HPV immunology Laboratory)
Claire Eklund (QC Cytology)
Martha Hutchinson (QC Cytology)
Mary Sidawy (Histopathologist)
Wim Quint (Virologist, HPV DNA Testing)
Leen-Jan van Doorn (HPV DNA Testing)
Linda Struijk (HPV DNA testing)