MEXICAN CERVICAL CANCER SCREENING STUDY II
This project took place in the State of Michoacán Mexico. Enrollment was conduced from December 2008 through March of 2009. Approximately 2500 women took part in the study.
The primary objective of this study is to design a cost-effective, highly sensitive and highly specific screening program able to be adapted to all socioeconomic levels in the State of Michoacán, Mexico.
Secondary Objectives are the following; 1) To Determine the comparative sensitivity and specificity of primary HPV screening (using self-sampling and direct sampling) using the Gen-Probe APTIMA HPV Assay for the detection of high-grade pre-cancer and cancer of the cervix, 2) To study the role of VIA to allow safe and effective treatment triage in screen positive women in Michoacán, Mexico, and 3) To determine if the new design for the HPV self-sampler device is a simple and comfortable tool for HPV detection.
After obtaining informed consent, women who met inclusion/exclusion criteria collected a self sample for HPV using the POI/NIH device and placed in PreservCyt to be processed using Hybrid Capture II and Gen-Probe APTIMA assays. Next, a physician collected a direct sample for HPV and Cytology. The physician collection device alternated between the Rover’s brush placed in PreservCyt and the Gen-Probe brush placed directly in Gen-Probe media.
Specimens were transferred to the POI laboratory in Morelia, Mexico. The cytology and the HC-II was processed in Mexico. The samples collected for Gen-Probe were shipped to Gen-Probe laboratories in San Diego for processing.
All participants were recalled on specific days as the study progressed to receive their HPV and cytology results. The patients that were HPV positive on any test and/or cytology greater than or equal to ASCUS (read at the Cleveland Clinic) were further evaluate by VIA, colposcopy and biopsy. VIA was used to identify lesions inappropriate for intermediate cryotherapy (high grade lesions defined as greater than or equal to 3 quadrants or suspicious of cancer). Colposcopy and biopsy were done using the POI biopsy protocol (link). Cryotherapy was done on any HPV positive women unless their lesions were identified as inappropriate for immediate cryotherapy, in which case women were referred for appropriate care. Women whose biopsies proved undertreated, were recalled for further treatment. (Biopsies read by Cleveland Clinic Gynecologic Pathology) Follow up was conducted at 6 months and has recently been completed at 2-2 1/2 years.
2 papers have been published (Int J Gynecol Cancer 2010 Nov;20(8):1415-23; Int J Gynecol Cancer. 2013 Mar; 23(3): 513-8.) reporting the acceptability of a POI self-collection device and the use of a mRNA primary screening assay respectively. A third paper has recently been accepted examining the 6 month and 2+ years follow-up after cryotherapy (Starks et.al. J Lower Genital Tract Disease) .
REFERENCES
1. Int J Gynecol Cancer. 2009 Jan;19(1):27-32. doi: 10.1111/IGC.0b013e318197f479.
The Mexican Cervical Cancer Screening Trial: self-sampling for human papillomavirus with unaided visual inspection as a secondary screen.
Belinson JL(1), Pretorius RG, Enerson C, Garcia F, Cruz EP, Belinson SE,
Yeverino García E, Brainard J.
Author information:
(1)Department of Obstetrics and Gynecology, Cleveland Clinic, Cleveland, OH,
USA.
The Mexican Cervical Cancer Screening (MECCS) study took place in the State of
Michoacán. Primary screening was by self-sampling for high-risk human
papillomavirus (HR-HPV). The objectives were to increase the specificity of
primary HPV screening by requiring 2 positive HPV tests 1 year apart in women
whose secondary screen was negative according to an acetic acid-aided visual
inspection (VIA). In addition, we postulated that the sensitivity of VIA would
be sufficient to identify large preinvasive lesions and cancers unsuitable for
cryotherapy if applied in a see-and-treat algorithm.A total of 8621 women (aged
30-50 years) were screened, and 14.3% were positive for HR-HPV. In phase 1,
11.9% of the HPV-positive women were VIA-positive and were referred for
colposcopy with directed and random biopsies. If VIA-negative, women repeated
the self-sample 1 year later to detect persistent HR-HPV (25.2% were positive).
If persistently HR-HPV-positive in phase 2, patients again had VIA, then all
women (both VIA-positive and -negative) received directed and random biopsies.
If cryotherapy had been used to treat HPV- and VIA-positive women in phase 1 or
persistent HR-HPV-positive (phase 2), the potential risk of undertreatment would
have been 4.1%, and 66.4% of the treated patients would have had normal or
cervical intraepithelial neoplasia I on biopsy. The VIA triage would refer 0.73%
of the patients to colposcopy owing to the lesion size, location, or the
presence of a cancer. On the basis of this pilot study, we are encouraged to
explore and evaluate a rapid, more sensitive, and more specific self-test.
DOI: 10.1111/IGC.0b013e318197f479
PMID: 19258937 [Indexed for MEDLINE]
2. Int J Gynecol Cancer. 2010 Nov;20(8):1415-23. doi: 10.1111/IGC.0b013e3181f58678.
Mexican Cervical Cancer Screening Study II: acceptability of human
papillomavirus self-sampler.
Arriba LN(1), Enerson CL, Belinson S, Novick L, Belinson J.
Author information:
(1)Department of Obstetrics and Gynecology, Cleveland Clinic, Cleveland, OH,
USA. lucybethnieves@hotmail.com
INTRODUCTION: Cervical cancer is the second most common cancer in women
worldwide. In countries like Mexico, cervical cancer early detection programs
have had a minimal impact on the incidence and death rates from cervical cancer.
Self-sampling for the presence of high-risk human papillomavirus is potentially
a more effective screening tool to reach women who have limited access to
community healthcare resources. The objective of this phase 2 trial was to
establish if the fourth generation Preventive Oncology International/National
Institutes of Health self-sampler device is well accepted by women of all
socioeconomic levels in Michoacán, Mexico.
METHODS: This is a prospective phase 2 trial. The patients used the
self-sampler, and then the acceptability questionnaire (14 multiple choice
questions) was completed with the assistance of nursing staff.
RESULTS: Two thousand five hundred seventeen patients completed the
questionnaire. The mean age of our patient population was 39 years. Eighty-six
percent of patients reported being comfortable when using the self-test, and 76%
preferred to do the test at the clinic. Ninety-one percent of patients said that
if their only choice was to perform the test at home they would perform it
rather than not perform the test. The major barriers for the use of self-sampler
identified by the women in the study were fear (75%), woman might not perform
the test because she does not feel ill (70%), women felt that husbands may stand
in women’s way of performing the test (66%), and lack of time (61%). Results
differed by location but not by history of Papanicolaou test.
CONCLUSIONS: Most patients reported being comfortable when using the Preventive
Oncology International/National Institutes of Health fourth generation
self-test. Most influential barriers identified by the acceptability
questionnaire were fear, lack of signs or symptoms of illness, husbands’
influence, cost, lack of time, being unable to read, and lack of trust in the
medical community.
DOI: 10.1111/IGC.0b013e3181f58678
PMID: 21051987 [Indexed for MEDLINE]
3. Int J Gynecol Cancer. 2013 Mar;23(3):513-8. doi: 10.1097/IGC.0b013e318280f3bc.
Primary cervical cancer screening and triage using an mRNA human papillomavirus assay and visual inspection.
Nieves L(1), Enerson CL, Belinson S, Brainard J, Chiesa-Vottero A, Nagore N,
Booth C, Pérez AG, Chávez-Avilés MN, Belinson J.
Author information:
(1)New Hanover Regional Medical Center, Wilmington, NC 28402, USA.
lucybethnieves@hotmail.com
OBJECTIVE: Mexican Cervical Cancer Screening Study II (MECCS II) seeks to
develop a highly sensitive and highly specific screening program able to be
adapted to all socioeconomic levels in Mexico. The objectives of MECCS II are
(1) to compare the sensitivity and specificity for cervical intraepithelial
neoplasia (CIN) 3 or cancer of self-collected vaginal specimens tested for
high-risk types of the human papillomavirus (HR-HPV) by APTIMA with those tested
for HR-HPV by Hybrid Capture 2 (HC2); and (2) determine the efficacy of
cryotherapy in the treatment of HR-HPV-positive and acetic acid-aided visual
inspection (VIA)-positive and -negative women after VIA triage.
METHODS: The study was conducted in rural Mexico. Women aged 30 to 50 years,
nonpregnant, with no history of hysterectomy or pelvic irradiation and varied
histories of screening, participated. A direct endocervical sample was tested
for cytology, HC2, and APTIMA assay (AHPV). Subjects positive on any test were
recalled for triage VIA, biopsies, and immediate cryotherapy. Tests were
compared using McNemar test.
RESULTS: Two thousand forty-nine patients have complete results. Mean age of the
patients was 39.2 years; 7.7% presented with ≥atypical squamous cells of
uncertain significance (ASCUS), 1.8% ≥low-grade squamous intraepithelial
neoplasia, and 0.5% ≥high-grade squamous intraepithelial neoplasia. Two percent
of patients had ≥CIN2, and 0.78% had ≥CIN3 (including 2 with invasive disease).
The sensitivity of ThinPrep (>ASCUS), HC2, and AHPV for >CIN3 for direct
endocervical collection was 87.5%, 100%, and 100%, respectively. The specificity
of ThinPrep (>ASCUS), HC2, and AHPV for >CIN3 was 94.1%, 92.2%, and 93.5%,
respectively. Specificities of HC2 and AHPV differed significantly. The overall
percentage of agreement among HPV assays (HC2 vs APTIMA) is 97%. Four hundred
sixty-nine women returned for VIA. Two hundred ninety-one women were treated
with cryotherapy.
CONCLUSIONS: The specificity of the APTIMA assay along with high sensitivity is
an advantage for primary screening. Follow-up evaluation will be important to
determine the true impact of potential undertreatment in the screening
algorithm. Self-sampling applications are explored.
DOI: 10.1097/IGC.0b013e318280f3bc
PMID: 23334437 [Indexed for MEDLINE]
4. J Health Care Poor Underserved. 2013 Nov;24(4):1448-59. doi:
10.1353/hpu.2013.0180.
Community health workers, social support and cervical cancer screening among high-risk groups in rural Mexico.
Elliott PF, Belinson SE, Ottolenghi E, Smyth K, Belinson JL.
BACKGROUND: Rural Mexico has a low screening prevalence and high burden of
cervical cancer. One strategy to increase screening coverage utilizes community
health workers (CHWs) to recruit high-risk women and address barriers.
METHODS: We conducted a systematic cross-sectional survey of 196 women residing
in Chiapas, Mexico who were recruited by either CHWs or traditional means for
screening. This analysis compares 110 rural women’s risk factors, attitudes and
knowledge of cervical cancer and socioeconomic factors stratified by type of
recruitment.
RESULTS: Women who were informed of screening by CHWs were more likely to be of
high risk sub-groups and report higher scores of social support but were also
more likely to endorse difficulty with access and fatalistic attitudes about
cancer.
DISCUSSION: Utilizing CWHs results in increased screening among high-risk women
and increased social support for screening among rural women, addressing a
significant barrier, but may have limited effects on other barriers.
DOI: 10.1353/hpu.2013.0180
PMID: 24185143 [Indexed for MEDLINE]
5. J Low Genit Tract Dis. 2014 Oct;18(4):333-7. doi: 10.1097/LGT.0000000000000029.
Mexican Cervical Cancer Screening Study II: 6-month and 2-year follow-up of HR-HPV women treated with cryotherapy in a low-resource setting.
Starks D(1), Arriba LN, Enerson CL, Brainard J, Nagore N, Chiesa-Vottero A,
Uribe JV, Belinson J.
Author information:
(1)1Cleveland Clinic Women’s Health Institute, Cleveland, OH; 2Prueba Para La
Vida A.C., Morelia, Mexico; 3Preventive Oncology International Inc., Cleveland
Heights, OH; 4Department of Pathology, Cleveland Clinic, Cleveland, OH;
5Department of Pathology, Hospital de la Mujer; and 6Department of Pathology,
Hospital Civil, Morelia, Mexico.
OBJECTIVE: To determine the efficacy and tolerance of cryotherapy in a visual
inspection with acetic acid (VIA) triage protocol after primary human
papillomavirus (HPV) screening in a low-resource setting.
MATERIALS AND METHODS: This continuous series conducted over 2 years enrolled
nonpregnant, high-risk HPV (HR-HPV)-positive women between the ages of 30 and 50
years, who resided in the state of Michoacán, Mexico, and had a history of no
Pap smear screening or knowledge of Pap smear results within the last 3 years.
These women were initially enrolled in the Mexican Cervical Cancer Screening
Study II (MECCS II) trial and were treated with cryotherapy after VIA triage.
They subsequently followed up at 6 months and 2 years for repeat VIA,
colposcopy, and biopsy.
RESULTS: A total of 291 women were treated with cryotherapy, of whom 226 (78%)
followed up at 6 months. Of these 226 women, 153 (68%) were HR-HPV-negative;
there were no findings of cervical intraepithelial neoplasia grade 2 (CIN2) or
worse. The remaining 73 women (32%) were HR-HPV-positive; of these women, 2 had
CIN2 and 3 had CIN3. Only 137 women followed up at 2 years. Of these 137 women,
116 were HR-HPV-negative and 21 were HR-HPV-positive. Of the 21 women positive
for HR-HPV, 9 had negative biopsy results, 11 had CIN1, and 1 had no biopsy. The
clearance rate of HR-HPV was 83% (95% confidence interval: 0.78-0.87). There
were no biopsy findings of CIN2 or worse at 2 years. Before cryotherapy, of the
226 women, 15 (6.6%) were positive for endocervical curettage (ECC) and 5 (2.2%)
were referred for surgical management. Of these 15 ECC-positive women, 10 (67%)
followed up at 6 months and it was shown that no patient was ECC positive at
that time point. Moreover, of the 15 ECC-positive women, 11 (73%) followed up at
2 years and it was shown that no patient was ECC positive at that time point. In
our study, VIA had a false-positive rate of 5%.
CONCLUSIONS: Cryotherapy was an effective, acceptable, and well-tolerated means
of treating cervical dysplasia in a low-resource setting.
DOI: 10.1097/LGT.0000000000000029
PMID: 24977628 [Indexed for MEDLINE]