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.

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.

Primary cervical cancer screening and triage using an mRNA human papillomavirus assay and visual inspection.

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.

The Mexican Cervical Cancer Screening Trial: self-sampling for human papillomavirus with unaided visual inspection as a secondary screen.

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.