National Comprehensive Cancer Network

Clinical Recommendations

JNCCN - The Journal of the National Comprehensive Cancer Network

Table of Contents - Volume 6 Number 1

• NCCN Clinical Practice Guidelines in Oncology™
• Cervical Cancer
• Cervical Cancer Screening
• Original Articles
• PET in Cervical Cancer — Implications for 'Staging', Treatment Planning, Assessment of Prognosis, and Prediction of Response
• Primary Management of Early Stage Cervical Cancer (IA1-IB) and Appropriate Selection of Adjuvant Therapy
• Chemotherapy for Advanced, Recurrent, and Metastatic Cervical Cancer
• The Potential Utility of HPV Genotyping in Screening and Clinical Management
• Cytology Versus High-Risk HPV Testing for Follow-up of HPV-Positive Women Without CIN
• Conservative Management of Adolescents With Abnormal Cytology and Histology

NCCN Clinical Practice Guidelines in Oncology™

Cervical Cancer
An estimated 11,150 new cases of cervical cancer will be diagnosed in the United States in 2007; 3670 deaths are expected from the disease. Although cervical cancer rates are decreasing among women in all racial and ethnic groups in the United States, the incidence remains high among Hispanic/Latino women and cervical cancer remains a major world health problem. The global yearly incidence of cervical cancer for 2002 was 493,243, with an annual death rate of 273,505. It is the third most common cancer in women worldwide; 78% of cases occur in developing countries, where cervical cancer is the second most frequent cause of cancer death in women. The substantial decline in incidence and mortality of cervical cancer in developed countries is believed to be from effective screening. Persistent human papillomavirus (HPV) infection is considered the most important factor contributing to the development of cervical cancer. Immunization against HPV, which prevents persistent infection with certain types of HPV, is therefore expected to prevent specific HPV cancer in women. Other epidemiologic risk factors associated with cervical cancer are a history of smoking, parity, contraceptive use, early age at onset of coitus, larger number of sexual partners, history of sexually transmitted disease, and chronic immunosuppression.

Cervical Cancer Screening
Despite a significant decrease in the incidence and mortality of cervical carcinoma in the United States, it remains a health issue for women worldwide. Cervical cytology screening is the current method for early detection, and the NCCN Cervical Cancer Screening Clinical Practice Guidelines in Oncology provide direction for evaluating and managing this screening process, including clarified and revised recommendations on screening techniques and intervals and follow-up of abnormal screening results, including colposcopy. Cervical cytology screening techniques include conventional Papanicolaou tests or liquid-based cytology. Human papillomavirus (HPV) DNA testing for primary cervical cancer has been approved by the FDA, and HPV DNA testing for high-risk virus types can also be used as a component of both primary screening and workup of abnormal cytology results. Testing for low-risk virus types is not useful. Colposcopy, along with colposcopically directed biopsies, has become the primary method for evaluating women with abnormal cervical cytologies. Special considerations for colposcopy performed during pregnancy are also discussed.

Original Articles

PET in Cervical Cancer — Implications for 'Staging', Treatment Planning, Assessment of Prognosis, and Prediction of Response
Michael A. Gold, MD

The use of functional imaging techniques such as 18-fluoro-deoxy-glucose positron emission tomography and positron emission tomography-computed tomography to manage patients with cervical cancer is constantly increasing. Current roles include pretreatment staging and the diagnosis of recurrent disease. Reports also show the ability to predict survival based on pre- and posttherapy scans. These techniques are not fool-proof, however, and reports of both false-negative and false-positive scans document some limitations. Future studies must further elucidate their exact roles in the management of this disease process.

Primary Management of Early Stage Cervical Cancer (IA1-IB) and Appropriate Selection of Adjuvant Therapy
Heidi J. Gray, MD

Cervical cancer is the third most common gynecologic malignancy in the United States; however, it is the leading gynecologic cancer worldwide. Because early-stage patients present a clinically heterogeneous group, primary treatment offered may either be surgery or radiotherapy. Standard surgery is either radical hysterectomy with lymphadenectomy (stage IA2-IB2) or simple hysterectomy for microinvasive disease (stage IA1). Interest is also growing in conservative fertility-sparing surgery via radical trachelectomy as an option for select patients with early-stage disease desiring future fertility. Using either radical surgery or radiation therapy in stage IB disease yields 5-year survival rates of 87% to 92%. The addition of postoperative adjuvant radiation with concurrent chemotherapy is recommended in patients with high- or intermediate-risk disease after radical hysterectomy to reduce risk of recurrence and improve progression-free survival.

Chemotherapy for Advanced, Recurrent, and Metastatic Cervical Cancer
David H. Moore, MD

When cervical cancer is beyond curative treatment with surgery or radiation therapy, the prognosis is poor, and palliation is the primary objective. Early prospective studies identified cisplatin as an active drug for advanced, metastatic, or recurrent cervical cancer, but study results suggest that other platinum analogues are inferior. Several phase III trials established cisplatin plus paclitaxel as standard therapy for comparison. Using pooled data from 3 Gynecologic Oncology Group (GOG) phase III studies, a predictive model was developed to better identify patients who are unlikely to respond to cisplatin-containing chemotherapy. The GOG is currently developing a phase III trial to investigate the impact of bevacizumab and a regimen containing topotecan instead of cisplatin in combination with paclitaxel chemotherapy and to externally validate the predictive model. This study has the potential to radically change standard care for cervical cancer chemotherapy. Furthermore, if the predictive model is upheld, patients with high-risk factors for treatment failure may be directed to chemotherapy regimens that do not include cisplatin or to investigational trials.

The Potential Utility of HPV Genotyping in Screening and Clinical Management
Philip E. Castle, PhD, MPH

Detection of specific human papillomavirus (HPV) genotypes, or HPV genotyping, may be useful for differentiating between women who are carcinogenic HPV-positive at lower and higher risk for cervical intraepithelial neoplasia (CIN) III or greater. Considerable evidence already exists that the absolute risk for cervical precancer and cancer (≥ CIN III) varies considerably among specific HPV genotypes, and that detection of HPV-16 and HPV-18 may have clinical usefulness, especially among women who tested positive for carcinogenic HPV and have negative cytology. Detection of persistent carcinogenic HPV is strongly associated with CIN III or greater and strongly predicts its development, and might be used to monitor the outcomes of HPV infections. However, several practical considerations must be addressed before HPV genotyping can be used in screening and clinical management.

Cytology Versus High-Risk HPV Testing for Follow-up of HPV-Positive Women Without CIN
Kristopher J. Kimball, MD, and Warner K. Huh, MD

Screening for cervical cancer is often considered the success story for cancer screening in the United States. However, much room for improvement still exists. For example, experts have yet to establish the best follow-up strategy for women with an abnormal Papanicolaou test and high-risk human papillomavirus (HPV) followed by a normal colposcopy or biopsy that is negative for cervical intraepithelial neoplasia. The incorporation of HPV testing has allowed the development of a more sensitive and cost-efficient strategy. This article presents a brief overview of related guidelines and current modalities and reviews selected studies. Future directions and a possible schema for clinical management of these patients are also included.

Conservative Management of Adolescents With Abnormal Cytology and Histology
Anna-Barbara Moscicki, MD

Adolescents remain vulnerable to human papilloma virus (HPV) infection because of certain physiologic characteristics inherent in this age group as well as common sexual behaviors, including lack of condom use. The commonness of HPV in this age group also results in frequent abnormal cytology. Fortunately, most of the infections are transient, with frequent clearance of HPV and the lesion. Current strategies for adolescents with abnormal cytology include conservative management, avoiding invasive procedures. For cytologic ASCUS or LSIL, management can be obtaining cytology only at 1-year intervals for up to 2 years before referral for colposcopy is necessary. For biopsy-proven cervical intraepithelial neoplasia (CIN) I, management is similar, with yearly cytology indefinitely or until high-grade squamous intraepithelial lesions or CIN II/III develops. CIN II in adolescents adherent to therapy can be managed with 6-month cytology and colposcopy.