Levi S. Downs

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age‐appropriate screening strategies, including the use of cytology and high‐risk human papillomavirus (HPV) testing, follow‐up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. CA Cancer J Clin 2012.

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer.

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections.

A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer

BACKGROUND Natural killer (NK) cells derived from patients with cancer exhibit diminished cytotoxicity compared with NK cells from healthy individuals. We evaluated the tumor response and in vivo expansion of allogeneic NK cells in recurrent ovarian and breast cancer. METHODS Patients underwent a lymphodepleting preparative regimen: fludarabine 25 mg/m(2) × 5 doses, cyclophosphamide 60 mg/kg × 2 doses, and, in seven patients, 200 cGy total body irradiation (TBI) to increase host immune suppression. An NK cell product, from a haplo-identical related donor, was incubated overnight in 1000 U/mL interleukin (IL)-2 prior to infusion. Subcutaneous IL-2 (10 MU) was given three times/week × 6 doses after NK cell infusion to promote expansion, defined as detection of ≥100 donor-derived NK cells/μL blood 14 days after infusion, based on molecular chimerism and flow cytometry. RESULTS Twenty (14 ovarian, 6 breast) patients were enrolled. The median age was 52 (range 30-65) years. Mean NK cell dose was 2.16 × 10(7)cells/kg. Donor DNA was detected 7 days after NK cell infusion in 9/13 (69%) patients without TBI and 6/7 (85%) with TBI. T-regulatory cells (Treg) were elevated at day +14 compared with pre-chemotherapy (P = 0.03). Serum IL-15 levels increased after the preparative regimen (P = <0.001). Patients receiving TBI had delayed hematologic recovery (P = 0.014). One patient who was not evaluable had successful in vivo NK cell expansion. CONCLUSIONS Adoptive transfer of haplo-identical NK cells after lymphodepleting chemotherapy is associated with transient donor chimerism and may be limited by reconstituting recipient Treg cells. Strategies to augment in vivo NK cell persistence and expansion are needed.

American cancer society, american society for colposcopy and cervical pathology, and american society for clinical pathology screening guidelines for the prevention and early detection of cervical cancer

Abstract An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from six working groups, and a recent symposium co-sponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16/18 infections.

The disparity of cervical cancer in diverse populations

Significant disparities in cervical cancer incidence and mortality rates among minority groups have been documented in the United States, despite an overall decline in these rates for the population as a whole. Differences in cervical cancer screening practices have been suggested as an explanation for these disparities, as have differences in treatment among various racial and ethnic groups. A number of factors are attributed to these observed differences. As minority populations continue to grow in size over the next 50 years, persistent disparities will place an ever increasing burden on these populations and on the national healthcare system. Strategies to reduce cervical cancer disparities need to be employed in order to reverse these trends.

Etiologic heterogeneity in endometrial cancer: Evidence from a Gynecologic Oncology Group trial☆

OBJECTIVE Although the epidemiology of typical endometrial carcinomas (grades 1-2 endometrioid or Type I) is well established, less is known regarding higher grade endometrioid or non-endometrioid carcinomas (Type II). Within a large Gynecologic Oncology Group trial (GOG-210), which included central pathology review, we investigated the etiologic heterogeneity of endometrial cancers by comparing risk factors for different histologic categories. METHODS Based on epidemiologic questionnaire data, risk factor associations, expressed as odds ratios (OR) with 95% confidence intervals (CI), were estimated comparing grade 3 endometrioid and Type II cancers (including histologic subtypes) to grades 1-2 endometrioid cancers. RESULTS Compared with 2244 grades 1-2 endometrioid cancers, women with Type II cancers (321 serous, 141 carcinosarcomas, 77 clear cell, 42 mixed epithelial with serous or clear cell components) were older; more often non-white, multiparous, current smokers; and less often obese. Risk factors for grade 3 endometrioid carcinomas (n=354) were generally similar to those identified for Type II cancers, although patients with grade 3 endometrioid tumors more often had histories of breast cancer without tamoxifen exposure while those with Type II tumors were more frequently treated with tamoxifen. Patients with serous cancers and carcinosarcomas more frequently had breast cancer histories with tamoxifen treatment compared to patients with other tumors. CONCLUSIONS Risk factors for aggressive endometrial cancers, including grade 3 endometrioid and non-endometrioid tumors, appear to differ from lower grade endometrioid carcinomas. Our findings support etiologic differences between Type I and II endometrial cancers as well as additional heterogeneity within Type II cancers.

Optimization of primary and secondary cervical cancer prevention strategies in an era of cervical cancer vaccination: A multi-regional health economic analysis

With the recent advent of cervical cancer vaccines, many questions relating to the best overall prevention methods for cervical disease are beginning to arise. A Markov model was used across five geographic regions (Canada, The Netherlands, Taiwan, UK, US) to examine the clinical benefits and cost-effectiveness of: (1) vaccination combined with screening, considering changes to screening-related parameters and (2) vaccination combined with screening, considering changes to screening policy. Given the assumptions used in this analysis, adding vaccination to current screening is likely to be cost-effective in the regions studied. When considering vaccination with several plausible changes to screening programmes, locations with the most frequent Papanicolaou smear testing may achieve the most efficiency gains by adopting a less frequent screening interval or incorporating HPV testing into their screening practices. Although it may be beneficial to change screening to maximize efficiency, the most cost-effective strategies for vaccination and screening combinations may not lead to the greatest reductions in cervical cancer; therefore such policy decisions may vary depending on region-specific goals. Finally, new screening paradigms such as primary HPV testing should be considered in future analyses.

A phase II study of fulvestrant in the treatment of multiply-recurrent epithelial ovarian cancer

Objective. The goal of treating recurrent ovarian cancer is disease control while minimizing toxicity. Fulvestrant, a novel estrogen receptor (ER) antagonist, has proven clinically beneficial and well-tolerated in treating recurrent breast cancer. Ovarian cancer often expresses ER and may respond to anti-estrogen therapy. We evaluated fulvestrant in women with recurrent ovarian or primary peritoneal cancer. Methods. Patients with ER-positive, multiply recurrent ovarian or primary peritoneal carcinoma and either measurable disease according to RECIST criteria or an abnormal and rising CA-125 were eligible for enrollment. Treatment consisted of single agent fulvestrant, 500 mg IM on Day 1, 250 mg IM on Day 15, and 250 mg IM on Day 29 and every 28 days thereafter until either intolerance or disease progression. Disease response was assessed by monthly physical exams and CA-125 levels as well as CT scans bimonthly. The primary endpoint was clinical benefit (CB=complete response (CR)+partial response (PR)+stable disease (SD)) at 90 days. Results. Thirty-one women were enrolled and 26 women (median age of 61) met inclusion criteria and received at least one dose. Patients had received a median of 5 prior chemotherapeutic regimens (range: 2-13). We observed one CR (4%), one PR (4%), and 9 patients with SD (35%) using modified-Rustin criteria (CA-125 level). Using modified-RECIST criteria 13 patients (50%) achieved SD. The median time to disease progression was 62 days (mean 86 days). Grade 1 toxicity included headache (1 patient) and bromidrosis (2 patients). Conclusions. Fulvestrant is well-tolerated and efficacious. Objective response rates are low, but disease stabilization was common.

Initial lessons learned in HPV vaccination.

In the recent period following the approval of the first vaccine targeted against human papillomavirus, it is imperative that we re-evaluate the past, present, and future of cervical cancer prevention. It is clear that the subject of vaccinating young women against a sexually transmitted infection has incited a candid debate among all groups involved. Therefore, we must make the most appropriate and accurate information available to the public and medical communities. The development of vaccines targeted against oncogenic human papillomavirus (HPV) types has made it possible to eliminate approximately 70% of all invasive cervical cancers in women worldwide. However, knowledge about HPV infection and cervical cancer, as well as the need to vaccinate against oncogenic HPV infection, is still lacking among women and physicians. This deficiency could be a key reason why some parents continue to have reservations about vaccinating their daughters. In order for HPV vaccination programs to be highly successful, multiple barriers must be overcome. Review of lessons learned to date has demonstrated that continued tailored and targeted educational and awareness initiatives are required for healthcare professionals, media, patients, and parents. This article also examines the impact of the HPV vaccination awareness campaign on media and public policy dynamics.

Anal human papillomavirus infection and abnormal anal cytology in women with genital neoplasia.

OBJECTIVES Describe the type-specific prevalence of anal HPV infection in women with lower genital tract intraepithelial neoplasia and cancer. Describe the prevalence of abnormal anal cytology and identify risk factors for anal HPV infection and abnormal anal cytology in this population. METHODS We performed a cross-sectional study of women attending 2 university-based colposcopy clinics with high-grade lower genital tract intraepithelial neoplasia or cancer. Participants received anal HPV testing/typing, anal cytology and completed a questionnaire detailing medical history and sexual behavior. RESULTS Of the 102 women enrolled, 92 (90%) had adequate beta-globin for analysis of HPV DNA status, and 47/92 women (51%) had detectable anal HPV. Of the 15 HPV types identified, 9 (60%) were oncogenic types and 6 (40%) were non-oncogenic or undetermined risk types. Overall, 9 women (9%) had abnormal anal cytology, and 7 of those had corresponding anal intraepithelial neoplasia grade I (AIN I). Women with vulvar disease had the highest proportion of abnormal anal cytology (21%) compared to women with cervical disease alone (7%), but this difference was not statistically significant (p=0.10). Neither anal HPV infection nor abnormal cytology was significantly associated with anal sex practices, smoking or number of sexual partners. CONCLUSIONS Anal infection with high-risk HPV types is common in women with high-grade genital neoplasia, but was not associated with known risk factors for genital HPV infection. Other unidentified risk factors may play a role in the anal HPV infection in this population. Abnormal anal cytology was rare and larger studies are needed to identify risk factors associated with abnormal cytology and anal intraepithelial neoplasia in this population.