Costa Rican Natural History Study of HPV and Cervical Neoplasia
Costa Rican Natural History Study of HPV and Cervical Neoplasia
A population-based study was initiated in Costa Rica in June 1993 to investigate the natural
 history of human papillomaviruses (HPV) and cervical neoplasia. Over a period of 18 months,
 ending in December 1994, 10,080 women were recruited into our study, after informed consent
 was obtained. At the initial recruitment visit, all women were administered a brief risk
 factor questionnaire, had 15ml of blood collected and, if sexually active, were given a
 pelvic examination. At the time of the pelvic examination, a Pap smear was collected, as were
 additional cervical cells which were then used for additional monolayer smears (ThinPrep) and
 for human papillomavirus and other testing. Pictures of the cervix, known as cervigrams, were
 also taken as a third screening test. Based on these screening tests, women were referred to
 colposcopy, at which time a more detailed risk factor questionnaire was administered,
 additional cervical cells and blood (15ml) were collected, and histological specimens were
 obtained, if indicated by the colposcopy. Women diagnosed with a high-grade cervical lesion
 (HSIL) or cervical cancer were treated by Social Security Administration clinicians using
 standard local protocols.

 Women without evidence of HSIL or cancer at enrollment comprise the group of subjects who
 have been followed as part of our longitudinal study. Three distinct groups of women of
 approximately equal size (about 3,000 women each) exist within our longitudinal cohort. The
 first group consists of women who at enrollment had evidence of low-grade cervical lesions
 (LSIL) or equivocal lesions and a sample of the remaining cohort members. This group is being
 followed actively at 6-12 month intervals through their seventh anniversary in the cohort.
 The second group consists of women who were cytologically normal at enrollment but randomly
 selected for active follow-up. This second group will be seen once after enrollment, at their
 fifth anniversary in the cohort. Women in this group with evidence of LSIL at the fifth
 anniversary visit will be added to the first group described above and followed at 6-month
 intervals. The final group consists of the remaining women in our cohort (all cytologically
 normal at enrollment). These women are being followed passively via linkage to the cytology
 and tumor registries in Cost Rica.

 Clinical visits conducted during follow-up consist of a brief personal interview that
 collects information on exposures since enrollment, the collection of 15ml blood, and a
 pelvic examination. Pap smear is prepared during the pelvic examination, and additional
 cervical specimens are collected and used to prepare a monolayer smear (ThinPrep) and for
 human papillomavirus and other testing. Similar to the enrollment visit, cervigrams are also
 collected from each participant at the time of their follow-up visits.

 During follow-up, women with any evidence of progression to HSIL or cancer (by Pap smear,
 ThinPrep, cervicography, or by visual inspection) are referred to colposcopy, censored from
 the study, and treated by Social Security Administration clinicians using standard local
 protocols.
A population-based study was initiated in Costa Rica in June 1993 to investigate the natural
 history of human papillomaviruses (HPV) and cervical neoplasia. Over a period of 18 months,
 ending in December 1994, 10,080 women were recruited into our study, after informed consent
 was obtained. At the initial recruitment visit, all women were administered a brief risk
 factor questionnaire, had 15ml of blood collected and, if sexually active, were given a
 pelvic examination. At the time of the pelvic examination, a Pap smear was collected, as were
 additional cervical cells which were then used for additional monolayer smears (ThinPrep) and
 for human papillomavirus and other testing. Pictures of the cervix, known as cervigrams, were
 also taken as a third screening test. Based on these screening tests, women were referred to
 colposcopy, at which time a more detailed risk factor questionnaire was administered,
 additional cervical cells and blood (15ml) were collected, and histological specimens were
 obtained, if indicated by the colposcopy. Women diagnosed with a high-grade cervical lesion
 (HSIL) or cervical cancers were treated by Social Security Administration clinicians using
 standard local protocols.

 Women without evidence of HSIL or cancer at enrollment comprise the group of subjects who
 were followed as part of our longitudinal study. Three distinct groups of women of
 approximately equal size (about 3,000 women each) exist within our longitudinal cohort. The
 first group consists of women who at enrollment had evidence of low-grade cervical lesions
 (LSIL) or equivocal lesions and a sample of the remaining cohort members. This group was
 followed actively at 6-12 month intervals through their seventh anniversary in the cohort.
 The second group consists of women who were cytologically normal at enrollment but randomly
 selected for active follow-up. This second group was seen once after enrollment, close to
 fifth anniversary in the cohort. Women in this group with evidence of LSIL at the fifth
 anniversary visit were added to the first group described above and followed at 6-month
 intervals. The final group consists of the remaining women in our cohort (all cytologically
 normal at enrollment). These women were followed passively via linkage to the cytology and
 tumor registries in Costa Rica.

 Clinical visits conducted during follow-up consisted of a brief personal interview that
 collects information on exposures since enrollment, the collection of 15ml blood, and a
 pelvic examination. A Pap smear was prepared during the pelvic examination, and additional
 cervical specimens were collected and used to prepare a monolayer smear (ThinPrep) and for
 human papillomavirus and other testing. Similar to the enrollment visit, cervigrams were also
 collected from each participant at the time of their follow-up visits.

 During follow-up, women with any evidence of progression to HSIL or cancer (by Pap smear,
 ThinPrep, cervicography, or by visual inspection) were referred to colposcopy, censored from
 the study, and treated by Social Security Administration clinicians using standard local
 protocols.
-  INCLUSION CRITERIA FOR FOLLOW-UP PHASE OF NATURAL HISTORY STUDY:

 Less than 35 years of age.

 Intact uterus (non-hysterectomized).

 In good general health.

 Non-pregnant.

 For women not using OCs: Having regular cycles [cycles 25-35 days in length].

 HPV16 seropositive [based on data from latest visit tested].

 No evidence of HSIL/cancer [based on data from latest visit within cohort].

 Willing to participate [informed consent].

 INCLUSION CRITERIA FOR FOLLOW-UP PHASE OF COHORT STUDY:

 Must be between the ages of 45 to 70 years.

 Women who do not have a final diagnosis of HSIL.