OBJECTIVES: To explore the implications of cervical conization specimens lacking the targeted high-grade squamous intraepithelial lesions (negative cone). METHODS: We studied 540 conization procedures: 400 positive cones and 140 negative cones. Clinicopathologic features and 2-year follow-up results were reported. RESULTS: Negative cones comprised 22% of procedures triggered by CIN2 or higher biopsies. Procedures triggered by cytology produced much higher percentages of negative cones (37% high-grade squamous intraepithelial lesion [HSIL], 46% atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion [ASC-H], and 76% low-grade squamous intraepithelial lesion-cannot exclude high-grade squamous intraepithelial lesion [LSIL-H]). Upon reviewing negative excision-triggering biopsy and cytology, we downgraded 24 (24%) CIN2 biopsies, three (14%) HSIL, five (83%) ASC-H, and 12 (92%) LSIL-H. One-third of our negative cones can be attributed to overdiagnosis either on biopsy or cytology. Patients with negative cones were older and had smaller excisions, negative colposcopic findings, and negative/equivocal high-risk human papillomavirus (HR-HPV). Within 2 years, 35 (25%) women with negative cones experienced ASCUS or LSIL. Only one (0.7%) recurred as CIN3, a significantly lower percentage than women with positive cones (13%). CONCLUSIONS: We advocate careful review of all excision-triggering biopsy and cytology, especially in cases of LSIL-H. Patients with negative cones should be surveyed with cytology and HR-HPV testing.

BACKGROUND: Pap test (PT) interpretations of low-grade squamous intraepithelial lesion (LSIL), cannot exclude high-grade squamous intraepithelial lesion (HSIL), or LSIL-H, are used in many laboratories; however monitoring its usage for quality assurance purposes is understudied. METHODS: PTs from 2005 to 2010 were collected, and yearly frequencies of LSIL, HSIL, LSIL-H, and atypical squamous cells, cannot exclude HSIL (ASC-H) as a function of total PTs and total squamous intraepithelial lesions (SILs) were calculated. Two-year risk of cervical intraepithelial neoplasia 2 (CIN2) or worse (CIN2+) and CIN 3 or worse (CIN3+) was calculated. RESULTS: A total of 352,220 PTs were identified including 17,301 abnormal PTs. LSIL-H usage increased from 2005 to 2010 (from 0.28% of total PTs in 2005 to 0.61% in 2010, P < .01; from 5.8% of total SILs in 2005 to 12% in 2010, P < .001). HSIL usage decreased significantly from 2005 to 2010 (from 0.7% of total PTs in 2005 to 0.48% in 2010, P = .048; from 14.5% of total SILs in 2005 to 9.5% in 2010, P < .01). Usage of LSIL and ASC-H did not change. Two-year risk of CIN2+ and CIN3+ for HSIL increased significantly from 2005 to 2010 (P < .01). Two-year risk of CIN2+ and CIN3+ for LSIL-H did not change significantly from 2005 to 2010. CONCLUSIONS: The frequency of LSIL-H interpretations is significantly increasing at our institution, with a significant decrease in HSIL interpretations over the same period. Two-year risk of CIN2+ and CIN3+ for HSIL increased significantly as usage of LSIL-H increased and that of HSIL decreased. Laboratories using LSIL-H may benefit from monitoring its frequency to ensure its appropriate use. Cancer (Cancer Cytopathol) 2014;122:123-7. (c) 2013 American Cancer Society.

Background: High risk human papillomavirus (HR HPV), including types 16 and 18, has been proven a causative factor of cervical cancer (Bosch et al., 2002). Recent guidelines allow for the option of HR HPV DNA testing as an adjunct to cervical cytology screening in women 30 years and older (ACOG Practice Bulletin, Number 45, 2003). Several worldwide studies demonstrate that HR HPV DNA testing is able to detect 85-100% of underlying high grade dysplasia (CIN 2,3) and cancer (Cuzick et al., 2006). HR HPV DNA testing using Hybrid Capture© 2 increases the sensitivity of detecting high grade dysplasia and cervical cancer over that of Pap smears alone. Negative predictive values when both screening tools are utilized ranged from 0.9888 to 1.000 (Sherman et al., 2003). Prospective studies indicate that women whose screening tests are both negative are at very low risk for developing high grade dysplasia or cervical cancer over the next three to five years. The cumulative incidence of biopsy-confirmed CIN 3 was 4.4% in HR HPV DNA positive women over 45 months versus 0.24% in HR HPV DNA negative women (Sherman et al., 2003). Thus, women who are HR HPV negative and have a negative Pap smear can wait three years until their next screening. It is known that the news of an abnormal Pap smear leads to heightened anxiety in women (Bell et al., 1995), but that education can reduce anxiety (Freeman-Wang et al., 2001). Common questions that women have about HPV have been studied, as well as what information they wish to receive about HPV (Anhang et al., 2004; Gilbert et al., 2003). This information becomes helpful when talking to women and providing educational materials on HPV and Pap smears. We hypothesize that news of being HR HPV positive will cause anxiety and questions among women. Recommended guidelines are to test for HR HPV with routine Pap smear screening in women 30 and older. Our concern is that women who are older and may be in a monogamous relationship may be reluctant to learn their HPV status. Because HPV is sexually transmitted, many women may be uncomfortable with being tested or even discussing HPV. How does an older, married woman feel about being tested for HPV when she comes in for her Pap smear? Do her feelings change after education on HPV and cervical cancer? These are the questions that the investigators wished to answer. Objectives: This study seeks to assess women’s knowledge, feelings, anxieties, and willingness for adjunct HR HPV testing along with their annual cervical cancer screening via Pap smear. It aims to determine whether education plays a role in improving knowledge, in relieving anxiety, and in willingness to be tested for HR HPV DNA as an adjunct to their Pap smear. Methods: Women age 30 years and older who presented for their annual gynecologic exam and Pap smear were asked to complete a pre-education and post-education questionnaire concerning HPV, cervical cancer, Pap smears, feelings about being tested for HPV, and whether these feelings change if cervical cancer detection is improved. The questionnaire asked about their concerns if they were to test positive for HR HPV. It asked about adherence regarding annual gynecologic exam if they did not need another Pap smear and HPV testing for three years. Between pre-education and post-education questionnaires, the participants were given educational material to read followed by a verbal discussion and opportunity to ask questions with one of the investigators. The pre-education and post-education questionnaires were identical, except for demographic questions on the pre-education version. When analyzing data trends, the questions were grouped into two categories: objective and subjective. The objective questions included those that tested knowledge base, whereas the subjective questions included questions aimed at ascertaining patients’ feelings, beliefs, and anxieties. All women who entered the study were being seen in a hospital-based obstetrics and gynecology faculty practice at the UMass Memorial Health Care (UMMHC)-Memorial Campus. The data was collated on an Excel spread sheet and questionnaires were assigned random identifiers for confidentiality purposes. Analysis was conducted utilizing SAS 9.1 (Copyright © 2002-2003 by SAS Institute Inc., Cary, NC, USA). Demographic characteristics were summarized using frequency measures. Comparisons between pre-education and post-education questionnaires were performed using Fisher’s Exact test. A p-value of <0.05 was used to identify relationships deemed to be statistically significant. Results: A total of 51 patients presenting for their annual gynecologic exams at the UMMHC Ob/Gyn faculty practice volunteered to complete pre-education and post-education questionnaires over the course of one visit. Of those 51 patients, 1 patient withdrew from the study after completing the consent form and prior to completing any questionnaires or receiving education. Among the remaining patients, 44% described themselves as Caucasian, 23% were in the age range of 40-49 years old, and 26% were college educated. Furthermore, 25% had a history of an abnormal Pap smear, while 39% reported they had never been diagnosed with HPV. The most common age for first vaginal intercourse was 15-18 years old (25%) and 26% of women reported having 2-5 sexual partners since becoming sexually active. Finally, 40% of women surveyed described their current relationship as she and her partner having sex with only each other and no participant reported she or her partner was having intercourse with someone else in addition to each other. When comparing correct answers on the pre-education versus post-education questionnaires, eight of the eleven knowledge based, multiple choice questions reached statistical significance at a level of p<0.0001. One additional question reached statistical significance to 0.0027. Only two of the knowledge based, multiple choice questions did not reach statistical significance. These two questions, which asked what a Pap is and why is it recommended, did not reach statistical significance because most women initially answered correctly on the pre-education questionnaire. Among the subjective questions, only one question reached statistical significance. This particular question asked if a woman were to test positive for HPV to what extent would she be concerned or not concerned. Pre-education, most women indicated that they would be concerned, with 30% reporting they would be somewhat concerned and 60% reporting that they would be very concerned. In comparison, post-education answers still reflected that women would be concerned, but showed a decrease in the degree of concern, with the largest percentage (58%) in the somewhat concerned category and less (27%) in the very concerned. Furthermore, when asked what specific concerns a woman may have if she were to test positive for HPV, 48% reported that she would be most worried that she might get cervical cancer, whereas none of the participants expressed primary concern that her partner was having sex with someone else. The remaining questions, while not statistically significant, showed interesting trends that provide valuable clinical information. After education, 77% of women were very likely to agree to be tested for HPV and 67% would be very likely to return for annual gynecologic exams even if a Pap smear were required only every three years. Discussion: Our study was limited by a small patient population that represented a mostly Caucasian and educated group of women. The results reflect the opinions of women already participating in health care maintenance activities and screening evaluations as those surveyed were presenting for their annual exams. Their knowledge about Pap smears and HPV may be greater than the general population since all those surveyed had previously had a Pap smear, with approximately half having had an abnormal Pap in the past. Future studies could be improved by clarifying the specific kind of abnormal Pap in the past, i.e. ASCUS, LGSIL. Assessment of the role of education was also limited by the short time duration between completion of pre-education and post-education questionnaires. Follow-up surveys in six months or one year would evaluate for long-term retention and further elucidate the effectiveness of education. The degree to which testing positive for HPV would make women concerned about monogamy may be less in our study than the general population as no participant reported that she or her partner was having sexual intercourse with anyone outside of their relationship. Finally, knowledge regarding HPV and its association with cervical cancer may have recently increased due to current mass media campaigns and this increased awareness may have affected the results of our study. Conclusion: Our study showed that education did play a role in improving women’s knowledge about HPV and its causal relationship with cervical cancer. In contrast to previous studies of this nature, most women surveyed did in fact know what a Pap smear was. Most women would be willing to get an HPV test and, while they would not feel particularly anxious about getting tested, most would be concerned if they were to test positive. Causing the highest amount of anxiety would be the concern that they might get cervical cancer. Interestingly, none of the women surveyed would be primarily concerned that her partner is having sex with someone else if she were to test positive. While most pre-education and post-education subjective answers were not statistically significant, the trend showed that education indeed reduced women’s anxiety about testing positive for HPV. Also, the majority of women reported that if they had a normal Pap smear and tested negative for HPV, they would still return for annual gynecologic exams even if they no longer needed a yearly Pap. This addresses current concerns among gynecologic providers that women’s adherence to annual exams may decrease if a yearly Pap smear is no longer required. This study highlights the importance of communication between physician and patient and emphasizes the role of education in increasing knowledge, decreasing anxiety, and addressing concerns women have about their health.