Abstract
Introduction
Pap cytology and high-risk human papillomavirus (HPV) DNA co-testing for women aged 30 and older are recommended for cervical cancer prevention. Our purpose was to evaluate the efficacy of this co-testing for predicting the risk of high-grade cervical intraepithelial neoplasia (CIN3) during a 3-year follow-up period.
Methods
A retrospective database search identified women aged 30 years or older who had baseline HPV and Pap cytology co-testing results in 2007 or 2008 and for whom 3-year follow-up results were available. The cumulative 3-year risks of CIN3 were calculated.
Results
Three-year follow-up data after baseline Pap/HPV co-testing were available for 1,986 women (mean age, 53 years). Of the 1,668 who had a baseline Pap-negative (Pap−)/HPV− co-testing result, 1,561 (93.6%) had a negative for intraepithelial lesions or malignancy follow-up Pap cytology result. Of 1,530 women who had follow-up Pap/HPV co-testing, 1,504 (98.3%) had a Pap−/HPV− result. The 3-year cumulative risk for CIN3 was highest for women with a baseline Pap+/HPV+ co-testing result (12.5%); the CIN3 risk was lower in those with a Pap−/HPV+ result (1.5%, P=0.0032) or a Pap−/HPV− result (0.06%; P<0.0001). The 3-year cumulative risk of CIN3 was significantly greater for women with a HPV+ result (4.8%) than for those with a HPV− result (0.06%; P<0.0001).
Conclusions
Pap cytology and HPV co-testing is valuable for stratifying CIN3 risk. Pap cytology and HPV co-screening at a 3-year screening interval carries a low risk of CIN3 for women who have a baseline Pap−/HPV− co-testing result.
Keywords: Papanicolaou test, Human Papillomavirus, Cervical Intraepithelial Neoplasia, Follow-up studies, Cancer screening tests
Introduction
High-risk genotypes of human papillomavirus (HPV) are responsible for the development of more than 99% of cervical carcinomas.1 Cervical cancer screening with Pap cytology and HPV DNA co-testing has demonstrated either increased detection of high-grade cervical intraepithelial neoplasms (CIN2/3) at the initial screening round or decreased rate of cervical cancer at the second screening round or both compared to Pap cytology testing alone, confirming that Pap and HPV co-testing has greater sensitivity than Pap testing alone in the detection of CIN3+.2–4
Pap cytology and high-risk HPV co-testing for cervical cancer prevention in women aged 30 years and older has been recommended in the United States by the American Society for Colposcopy and Cervical Pathology (ASCCP). In the 2002 and the 2004 interim guidelines for cervical cancer screening5, 6, a 3-year screening interval was recommended for women with negative Pap (Pap−) and negative HPV (HPV−) test results.5,6 The current guidelines, issued in 2012 by the American Cancer Society, ASCCP, and the American Society for Clinical Pathology, recommend a 5-year screening interval for women aged 30 years and older with Pap−/HPV− co-testing results.7 This recommendation is based on published data demonstrating that the risks of CIN2+ and cervical carcinoma in women with Pap−/HPV− co-testing results for a 5-year interval are comparable to those in women with a Pap− cytology result for a 3-year interval. Therefore, the risk of co-screening with Pap and HPV at the longer interval is considered small and acceptable.8, 9
Although Pap cytology and HPV co-screening has been increasingly adopted by hospitals and cervical cancer screening programs in the U.S. for women aged 30 years and older, the practice is still relatively underused.10, 11 Published studies on Pap/HPV co-testing are limited.12–15 Therefore, observation of Pap/HPV co-screening in diverse samples/cohorts is required to document the risk involved in the longer screening interval for Pap/HPV co-screening in women aged 30 years and older. Furthermore, knowledge of the risks of CIN2/3 stratified by HPV/Pap co-screening results can be valuable for clinical triage and follow up for women at high risk for high-grade CIN, especially CIN3. To evaluate the risk of CIN3 in women with Pap and HPV co-screening results over greater screening intervals, we conducted a 3-year follow-up study of women who visited our Cancer Prevention Center for cervical cancer screening in 2007 and 2008.
Patients and Methods
Patient population
From the institutional patient database of The University of Texas MD Anderson Cancer Center, we retrospectively retrieved 10,302 Pap/HPV co-testing results from 8,206 women who visited the Cancer Prevention Center from January 2007 to December 2011. From the women who underwent screening in 2007 and 2008, we identified 1,986 women who had baseline Pap cytology and HPV co-testing results and were aged 30 years or older at the time of the baseline co-testing, and for whom follow-up results up to 3 years after the baseline HPV and Pap co-testing were available. These women ranged in age from 30 to 81 years (mean, 53 years, median, 54 years), and their ethnic backgrounds comprised white (1,520; 76.5%), Hispanic (180; 9.0%), African American (168; 8.5 %), Asian (105; 5.3%), and other or unspecified (13; 0.7%). The protocol for this study was approved by our Institutional Review Board.
Pap cytology and HPV co-testing
Pap cytology specimens were collected using the SurePath Pap collecting device (BD Diagnostics, TriPath Imaging, Burlington, NC, USA). The Pap specimens were prepared at the cytopathology laboratory of our institution and screened by cytotechnologists according to the Bethesda System for reporting Pap test results.16 Each Pap specimen classified as abnormal was reviewed by a cytopathologist.
HPV testing also was done in the Pap specimens. The residual SurePath specimen was sent to Quest Diagnostics (Houston, TX) for HPV DNA testing. HPV DNA was detected by the Hybrid Capture 2 assay (HC2; Qiagen, Valencia, CA), which collectively tests for 13 high-risk HPV types.
Follow-up biopsy
Women with an abnormal follow-up Pap and/or HPV result underwent colposcopy and/or biopsy in the Cancer Prevention Center according to the guidelines issued by ASCCP.13 The follow-up biopsy specimens were processed and interpreted by Department of Pathology pathologists at our institution.
Data analysis
The baseline Pap/HPV co-testing results were stratified according to Pap and/or HPV testing results. Cumulative risks (incidence) of CIN3 during the 3-year follow-up period were calculated, and descriptive statistics were used to compare groups. The Fisher’s exact test was used to assess the association between categorical variables. Tests with a P-value (2-sided test) less than 0.05 were considered significant. All computations were carried out using SAS version 9.4 (SAS Institute, Cary, NC).
Results
Baseline Pap cytology and HPV co-screening results
A total of 6,357 women underwent baseline Pap cytology and HPV co-testing at the Cancer Prevention Center during the 2007–2008 study period, 4,392 in 2007 and 1,965 in 2008. The baseline Pap and HPV co-testing results for these women are summarized in Table 1. Of the 6,044 (95.1%) women who had a baseline Pap− cytology testing result, 5,851 (96.8%, or 92.0% of the total cohort) had a HPV− result and 193 (3.2%, or 3.0% of the total cohort) had an HPV+ result. Among the total cohort of 6,357 women, 272 (4.3%) had an abnormal Pap testing result, including atypical squamous cells of undetermined significance (ASC-US); atypical squamous cells, cannot rule out high-grade squamous intraepithelial lesion (ASC-H); atypical glandular cells of undetermined significance (AGC); low-grade squamous intraepithelial lesion (LSIL); or high-grade squamous intraepithelial lesion (HSIL). Forty Pap cytology specimens (0.6%) were unsatisfactory. Another revealed endometrial carcinoma. The distribution of HPV results in Pap specimens with abnormal Pap results is summarized in Table 1. After exclusion of the 40 Pap specimens with unsatisfactory results and the one with endometrial adenocarcinoma, the baseline Pap/HPV co-testing results were divided into four categories: Pap−/HPV−, 5,851 (92.6%); Pap−/HPV+, 193 (3.1%); Pap+/HPV−, 185 (2.9%); and Pap+/HPV+, 87 (1.4%).
Table 1.
Baseline Pap Cytology and HPV Testing Results for Women Aged 30 Years and Older
| Pap Cytology | Pap cases (%) | HPV+ (%) |
|---|---|---|
| NILM | 6,044 (95.1) | 193 (3.2) |
| ASC-US | 171 (2.7) | 28 (16.4) |
| ASC-H | 14 (0.2) | 6 (42.9) |
| AGC | 14 (0.2) | 1 (0.7) |
| LSIL | 66 (1.0) | 45 (68.2) |
| HSIL | 7 (0.1) | 7 (100.0) |
| Adenocarcinoma* | 1 (0.02) | 0 |
| Unsatisfactory | 40 (0.6) | 4 (10.0) |
| Total | 6,357 (100.0) | 284 (4.5) |
Endometrial carcinoma
NILM, negative for intraepithelial lesion or malignancy; ASC-US, abnormal squamous cells of undetermined significance; ASC-H, abnormal squamous cells—cannot rule out high-grade squamous intraepithelial lesion; AGC, abnormal glandular cells of undetermined significance; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion.
Follow-up data were available for 1,986 women who had a baseline Pap/HPV co-testing result, including 1,896 Pap cytology results and 183 biopsy findings. The age distribution for these women is provided in Table 2. Pap−/HPV+ (31.6%) or Pap+/HPV+ (39.3%) baseline co-testing results were observed more frequently in the 40–49 year age group. A Pap+/HPV− baseline co-testing result was seen more frequently in the 50–59 year age group.
Table 2.
Age Distribution of Women with Baseline Pap/HPV Co-testing
| Age, years | ||||||
|---|---|---|---|---|---|---|
| Baseline Co-testing | 30–39 (%) | 40–49 (%) | 50–59 (%) | 60–69 (%) | ≥70 (%) | Total |
| Pap−/HPV− | 128 (7.7) | 570 (34.2) | 778 (46.6) | 162 (9.7) | 30 (1.8) | 1,668 |
| Pap−/HPV+ | 9 (6.8) | 42 (31.6) | 35 (26.3) | 34 (25.5) | 13 (9.8) | 133 |
| Pap+/HPV− | 12 (9.3) | 42 (32.5) | 53 (41.1) | 13 (10.1) | 9 (7.0) | 129 |
| Pap+/HPV+ | 7 (12.5) | 22 (39.3) | 16 (28.6) | 8 (14.3) | 3 (5.3) | 56 |
| Total | 156 (7.9) | 676 (34.0) | 882 (44.4) | 217 (10.9) | 55 (2.8) | 1,986 |
Three-year Pap/HPV cytology follow up
Of the 1,896 women who underwent a follow-up Pap test within 3 years after baseline Pap/HPV co-testing, 1,668 (88.0%) had a baseline Pap−/HPV− co-testing result, 132 (7.0%) a baseline Pap−/HPV+ result, 89 (4.6%) a baseline Pap+/HPV− result, and 7 (0.4%) a baseline Pap+/HPV+ co-testing result. The Pap cytology follow-up results for women with a baseline Pap/HPV co-test result are summarized in Table 3.
Table 3.
Follow-up Pap Cytology within 3 years of Baseline Pap/HPV Co-testing
| Follow-up Pap Cytology Result | |||||||
|---|---|---|---|---|---|---|---|
| Baseline Co-testing | NILM (%) | ASC-US (%) | AGC (%) | ASC-H (%) | LSIL (%) | HSIL (%) | Total |
| Pap−/HPV− | 1,561 (93.6) | 81 (4.9) | 6 (0.4) | 4 (0.2) | 15 (0.9) | 1 (0.1) | 1,668 |
| Pap−/HPV+ | 106 (80.3) | 15 (11.4) | 0 - | 3 (2.3) | 7 (5.3) | 1 (0.8) | 132 |
| Pap+/HPV− | 82 (92.1) | 3 (3.4) | 0 - | 0 - | 4 (4.5) | 0 - | 89 |
| Pap+/HPV+ | 3 (42.9) | 0 - | 0 - | 0 - | 4 (57.1) | 0 - | 7 |
| Total | 1,752 (92.4) | 99 (5.2) | 6 (0.3) | 7 (0.4) | 30 (1.6) | 2 (0.1) | 1,896 |
NILM, negative for intraepithelial lesion or malignancy; ASC-US, abnormal squamous cells of undetermined significance; ASC-H, abnormal squamous cells—cannot rule out high-grade squamous intraepithelial lesion; AGC, abnormal glandular cells of undetermined significance; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion
Pap+: ASC-US and higher
Of these 1,896 women, 1,752 (93.4%) had a negative for intraepithelial lesions of malignancy (NILM) Pap result. Of the 1,668 women with a baseline Pap−/HPV− co-testing result and a follow-up result available, 1,561 (93.6%) had a NILM Pap follow-up result. Of these 1,668 women, 1,530 had a follow-up Pap/HPV co-testing result, which was Pap−/HPV− in 1,504 (98.3%). The 3-year cumulative new HPV infection rate in women with a baseline Pap−/HPV− co-testing result and a follow-up co-testing result was 1.7% (26/1,530). The 3-year cumulative rate of abnormal follow-up Pap results was 6.4% (107/1,668) in women with a baseline Pap−/HPV− co-testing result, including 15 women with a LSIL result and one with a HSIL result.
In women with a baseline Pap−/HPV+ co-testing result, the 3-year cumulative HPV+ rate was 23.8% (24/101) and the 3-year cumulative rate of abnormal follow-up Pap results was 19.7% (26/132), including 7 LSIL and one HSIL. In women with a baseline Pap+/HPV− result, the 3-year cumulative HPV+ rate was 2.6% (2/77) and the 3-year cumulative rate of abnormal follow-up Pap results was 7.9% (7/89).
Three-year follow-up biopsy
During the 3-year follow-up period, 183 women with a baseline Pap/HPV co-testing result underwent cervical biopsy. CIN was diagnosed in 58 of these (34 cases of CIN1, 14 cases of CIN2, and 10 cases of CIN3). The cumulative risk of CIN was stratified and calculated by the number of women in each baseline Pap/HPV co-testing category (Table 4) or by baseline Pap cytology or HPV testing category (Table 5) with all available follow-up results, including both Pap and biopsy results. Table 4 illustrates the risks of CIN in women with a baseline Pap/HPV co-testing result. The highest 3-year cumulative risk for CIN3 was observed in women with a baseline Pap+/HPV+ co-testing result (12.5%); the rates were lower in women with a baseline Pap−/HPV+ (1.5%) or Pap−/HPV− (0.06%) co-testing result. None of the women with a baseline Pap+/HPV− result was shown to have a CIN3 result on follow-up biopsy (Table 4). The risk of CIN3 was significantly different between women with a baseline Pap−/HPV− co-testing result and those with a baseline Pap−/HPV+ co-testing result (P=0.0155) or those with a baseline Pap+/HPV+ co-testing result (P<0.0001). Similarly, the highest 3-year cumulative risks for CIN2 or CIN1 were observed in women with a baseline Pap+/HPV+ co-testing result; these risks were successively lower in women with a baseline Pap−/HPV+, Pap+/HPV−, or Pap−/HPV− co-testing result (Table 4). Age stratification demonstrated similar CIN3 risk level in women in the 30–39 year age group (1/156, 0.64%), in 40–49 year age group (4/676, 0.59) or in 50–59 year age group (5/882, 0.57%). No CIN3 cases were observed in women aged 60 or older.
Table 4.
Three-year Follow-up Biopsy Results in Women with Baseline Pap/HPV Co-testing
| Biopsy Result | |||||
|---|---|---|---|---|---|
| Baseline Co-testing | <CIN1 | CIN1 (%) | CIN2 (%) | CIN3 (%) | All women with follow-up |
| Pap−/HPV− | 46 | 6 (0.36) | 2 (0.12) | 1 (0.06) | 1,668 |
| Pap−/HPV+ | 21 | 11 (8.3) | 3 (2.3) | 2 (1.5) | 133 |
| Pap+/HPV− | 35 | 5 (3.9) | 2 (1.6) | 0 - | 129 |
| Pap+/HPV+ | 23 | 12 (21.4) | 7 (12.5) | 7 (12.5) | 56 |
| Total | 125 | 34 (1.8) | 14 (0.7) | 10 (0.5) | 1,986 |
CIN, cervical intraepithelial neoplasm
Table 5.
Three-year Follow-up Biopsy Results in Women with Baseline Pap or HPV Testing
| Biopsy Result | |||||
|---|---|---|---|---|---|
| Baseline Testing | <CIN1 | CIN1 (%) | CIN2 (%) | CIN3 (%) | All women with follow-up |
| Pap− | 67 | 17 (0.9) | 5 (0.28) | 3 (0.17) | 1,801 |
| Pap+ | 58 | 17 (9.2) | 9 (4.9) | 7 (3.8) | 185 |
| HPV− | 81 | 11 (0.6) | 4 (0.2) | 1 (0.06) | 1,797 |
| HPV+ | 44 | 23 (12.2) | 10 (5.3) | 9 (4.8) | 189 |
CIN, cervical intraepithelial neoplasm
When the baseline results were analyzed separately by individual test, that is, HPV or Pap, women with a baseline HPV+ testing result had a significantly higher risk for CIN3 (4.8%) than those with a baseline HPV-testing result (0.06%, P<0.0001). Similarly, women with a baseline Pap+ testing result had a significantly higher risk for CIN3 (3.8%) than those with a baseline Pap-testing result (0.17%, P<0.0001). The risks of CIN2 or CIN1 showed similar patterns (Table 5).
Discussion
In this retrospective study, we reviewed the 3-year follow-up data, including Pap cytology, Pap/HPV co-testing, and biopsy, for women who underwent baseline Pap/HPV co-testing screening in the Cancer Prevention Center of our institution over a 2-year period. We observed a very low 3-year cumulative risk of CIN3+ (0.06%) in women with a baseline Pap−/HPV− co-testing result. The highest cumulative risk of CIN3 was seen in women with a baseline Pap+/HPV+ co-testing result, with lower risks for women with a baseline Pap−/HPV+ or Pap+/HPV− co-testing result. Our findings indicate that Pap/HPV co-testing has a high efficacy in screening the population of women aged 30 and older and support using Pap/HPV co-testing for cervical cancer prevention as recommended by the current guidelines. Our findings also suggest that stratifying risk by Pap/HPV co-testing results may help optimize patient triage and follow up.
In 2007, we adopted the recommendation of the U.S. guidelines for cervical cancer prevention and began using Pap/HPV co-testing routinely for women aged 30 years and older. While 4,392 women underwent Pap/HPV co-testing at our Cancer Prevention Center during 2007, that number dropped to 1,965 in 2008 because of adoption of the 3-year screening interval, representing a 65.3% decline. For the same reason, only 5.3% of women who had a baseline Pap−/HPV− co-testing result came back during the first year for follow-up co-testing.
The fact that only 1,986 of the 6,357 women who underwent baseline screening at our center during the 2-year study period had follow-up testing results, either Pap cytology or biopsy, during the 3-year follow-up period may be attributed to the patient population screened at our cancer center. Many of the patients visiting our center for cancer diagnosis or therapy come from other regions or states, and most received follow-up screening for cervical cancer prevention near their home. Therefore, our study cohort represents a predominantly local, low-risk population similar to that previously reported in the Houston area.17 Furthermore, the women in our study cohort were from the cervical cancer screening population seen in our Cancer Prevention Center, and therefore were separate from patients with cervical dysplastic lesions, who were treated and monitored in the Gynecology Clinics of our institution. The baseline Pap/HPV co-testing results in our study are similar to the published data on the Kaiser Permanente Northern California (KPNC) cohort (Pap−/HPV−, 92.6% vs 92.5%; Pap−/HPV+, 3.1% vs 3.7%; Pap+/HPV−, 2.9% vs 2.5%, and Pap+/HPV+, 1.4%, vs 1.4%).13 The main difference between the two studies is the older age of the women in our study cohort (median, 54 years, while the median age of the KPNC cohort was 46 years). Consequently, the HPV positivity rate in women with ASC-US was relatively low, which is consistent with the data reported from a large study cohort in the U.S.10 In our study cohort, no cervical or endocervical carcinoma cases were identified during the 3-year follow-up period, most likely because of the low-risk and relatively older screening population. Therefore, we used CIN3 as an end disease for risk assessment during the 3-year follow-up period after baseline Pap/HPV co-testing.
Several published studies have examined Pap/HPV co-testing for women aged 30 years and older in the U.S. Katki et al. investigated co-testing in a large cohort of KPNC patients.9 Using the HC2 HPV assay to identify HPV, they reported a 3-year cumulative risk for CIN3+ of 0.047% and a 5-year cumulative risk of 0.16% in women with a baseline Pap−/HPV− co-testing result. In another published study of Pap/HPV co-testing that used the HC2 HPV assay, Zhao et al. reported a cumulative risk of 0.17% for CIN3+ in women with a baseline Pap−/HPV− co-testing result, but the follow-up period in that study was longer than 3 years (mean, 44 months).18 In a published study of a large cohort (ATHENA, Addressing the Need for Advanced HPV Diagnostics), Wright et al. reported a 3-year cumulative risk of 0.3% for CIN3+ in women with a baseline Pap−/HPV− co-testing result.19 Thus the 3-year cumulative risk of 0.06% for CIN3 in women with a baseline Pap−/HPV− co-testing result in our study is in the lower range of the risks reported in the published studies. The reason for the differences in the reported cumulative risk of CIN3 among the ATHENA and KPNC studies and our study is not clear. Although a different HPV assay was used in the ATHENA study (Cobas HPV assay, Roche Diagnostics, Indianapolis, IN), the differences in cumulative CIN3+ risk of these studies may reflect differences in the study population rather than in the testing method. The baseline HPV+ rate was higher (10.5%) in the ATHENA study cohort than in our study cohort (4.5%). The rate of abnormal baseline Pap cytology testing results (ASC-US and higher) was also higher in the ATHENA study cohort (6.4%) than in ours (4.3%), indicating that the ATHENA study cohort represented a higher risk population while ours represented a low-risk population.19 Nevertheless, the ATHENA study demonstrated that the 3-year cumulative risk for CIN3+ was significantly lower in women with a baseline Pap−/HPV− co-testing result (0.3%) than in women with a Pap− cytology testing result alone (0.8%), supporting the recommendation that integrating HPV testing into cervical cancer screening can significantly improve the efficacy of the screening for cervical cancer prevention.19 Blatt et al, in a retrospective study of Pap/HPV co-testing results in women undergoing cervical biopsies, reported that a positive Pap/HPV co-testing result had a higher efficacy for CIN3+ than either a positive HPV-only result or a positive Pap-only result. However, the cumulative risk of CIN3 in women with Pap−/HPV− cannot be assessed because of the study design. 15
The screening interval for Pap/HPV co-testing for women aged 30 years and older was extended from 3 years to 5 years in the revised U.S. guidelines issued in 2012.7 Even though Pap/HPV co-testing has been increasingly adopted in the U.S., rescreening within 3 years is still common.10, 11, 13 This may reflect the reluctance of clinicians or women to wait 5 years for rescreening. Recently, the increased cervical cancer risk associated with longer screening intervals has drawn concerns about the 5-year screening interval now recommended. The report by Katki et al. that the cumulative CIN3+ risk in the KPNC study over a 5-year screening interval (0.16%) was 3-fold higher than that over a 3-year interval (0.047%) and the report by Gage et al. that cancer risk doubled from 0.007% at 3 years to 0.014% at 5 years after a Pap−/HPV− co-testing result highlight the question of whether a 5-year rescreening interval is as safe as a 3-year rescreening interval for cervical cancer prevention.9, 20 In a more recent study, Gage et al. also reported a greater overall cumulative risk of CIN3 when the rescreening interval was extended from 3 years (0.39% in the New Mexico HPV Pap Registry [NMHPVPR], 0.46% in KPNC) to 5 years (0.54% in NMHPVPR, 0.59% in KPNC) for women with a Pap−/HPV− co-testing result.14 The clinical implication of prolonged rescreening interval after Pap/HPV co-testing remains uncertain because the published data on a 5-year follow-up interval are very limited. Luyten et al. compared CIN3+ rates at baseline Pap/HPV co-testing and at 5-year follow-up screening and found a significant decrease of CIN3+ rate from the baseline screening (0.87%) to the 5-year follow-up screening (0.05%).21 Although it was not clear whether the decline in CIN3+ rate was age-associated, as documented in published studies,14, 22 the study demonstrated a very low risk of CIN3+ after Pap/HPV co-testing even at a 5-year screening interval.
Our observations support the use of HPV testing results for risk stratification (Figure 1). An HPV+ result predicted a higher risk of CIN3 than a Pap+ cytology result. Our 3-year follow-up biopsy data showed a significantly lower risk of CIN3 (0.06%) in women with a HPV− test result than in women with a HPV+ result (4.8%). Our findings also indicate that risk stratification by Pap/HPV co-testing result is more accurate for risk prediction of CIN3+ than Pap test alone, a conclusion in keeping with the findings from large study cohorts such as the KPNC.9
Figure 1. Three-year Risk of CIN in Women with Baseline Pap and HPV Co-testing.
CIN, cervical intraepithelial neoplasm
When using high-risk HPV testing as a primary screening method for cervical cancer prevention, a 3-year rescreening interval is preferred because the prospective U.S. data are insufficient to support rescreening intervals beyond 3 years.23, 24 Our data show that if HPV testing were used as a primary screening tool, the CIN3 risk associated with a HPV− result would be the same as that associated with a Pap−/HPV− co-testing result (Table 4). However, the risk for CIN2 would be increased from 0.12% in women with a Pap−/HPV− co-testing result to 0.2% in women with a HPV− testing result. Our data are limited, however, in that they represent a relatively small cohort with low numbers of end diseases (>CIN3) in a low-risk population.
With the U.S. Food and Drug Administration approval of the Cobas HPV testing assay for primary cervical cancer screening and the new guidelines recommending HPV-based cervical cancer screening, further clinical studies are required to compare the efficacy of HPV alone and Pap/HPV co-testing for cervical cancer prevention.
Acknowledgments
The authors thank Ms. Kathryn L. Hale for editing the manuscript.
Footnotes
The authors have no conflicts to disclose or financial interests in the commercial products mentioned in this report.
Author Contributions:
Ming Guo: Conceptualization, Methodology, Validation, Formal analysis, Investigation, Resources, Data curation, Writing – original draft, Writing – review and editing, Visualization, Supervision, Project administration
Abha Khanna: Validation, Investigation, Resources, Data curation
Jianping Wang: Methodology, Validation, Investigation
Marilyn Dawlett: Investigation, Resources, Writing – review and editing
Teresa Kologinczak: Investigation
Genevieve Lyons: Formal analysis, Data curation, Writing – review and editing
Roland Bassett Jr.: Software, Formal analysis, Writing – review and editing
Nour Sneige: Conceptualization, Methodology, Writing – review and editing, Supervision
Yun Gong: Conceptualization, Methodology
Therese Bevers: Conceptualization, Formal analysis, Writing – review and editing
This study was presented in part at the 60th Annual Conference of the American Society of Cytopathology, Las Vegas, NV, November 2–6, 2012, and the 62nd Annual Conference of the American Society of Cytopathology, Dallas, TX, November 14–18, 2014. The study was supported in part by the Department of Pathology of The University of Texas MD Anderson Cancer Center and in part by the NIH/NCI under award number P30 CA016672.
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