years of age should not be screened by any method and that women 21 to 29 years of age should be screened by cytology alone every 3 years. For women 30 to 65 years of age, it is recommended that co-testing by cytology and HPV molecular detection occur every 5 years. In addition, the ACS/ASCCP/ASCP guidelines state that primary HPV testing in the absence of cytology for women 30 to 65 years old is not recommended. Screening can be discontinued in posthysterectomy patients and after 65 years of age if the woman has a history of adequate screening. Screening should take place as above, independent of the woman’s vaccination status. These recommendations do not apply to women who have been diagnosed with a high-grade dysplasia or cervical cancer, are immunocompromised, or were exposed to diethylstilbestrol in utero, who need more frequent screening. Diethylstilbestrol is a synthetic nonsteroidal estrogen that was used in the U.S. from 1938 to 1971 to prevent miscarriage and other pregnancy complications and has been shown to be associated with increased reproductive cancers.
TABLE 6.1 THE BETHESDA CLASSIFICATION SYSTEM FOR CERVICAL SQUAMOUS CELL DYSPLASIAa
| BETHESDA SYSTEM 1999 | BETHESDA SYSTEM 1991 | CIN SYSTEM | INTERPRETATION |
| Negative for intraepithelial lesions or malignancy | Within normal limits | Normal | No abnormal cells |
| ASC-US (atypical squamous cells of undetermined significance) | ASCUS (atypical squamous cells of undetermined significance) | Squamous cells with abnormalities greater than those attributed to reactive changes but that do not meet the criteria for a squamous intraepithelial lesion | |
| ASC-H (atypical squamous cells, cannot exclude HSIL) | |||
| LSIL (low-grade squamous intraepithelial lesions) | LSIL (low-grade squamous intraepithelial lesions) | CIN 1 | Mildly abnormal cells; changes are almost always due to HPV |
| HSIL (high-grade squamous intraepithelial lesions) with features suspicious for invasion (if invasion is suspected) | HSIL (high-grade squamous intraepithelial lesions) | CIN 2/3 | Moderately to severely abnormal squamous cells |
| Carcinoma | Carcinoma | Invasive squamous cell carcinoma; invasive glandular cell carcinoma (adenocarcinoma) | The possibility of cancer is high enough to warrant immediate evaluation but does not mean that the patient definitely has cancer |
a From reference 1.
Additional guidelines exist for managing patients with abnormal cytology results and/or a positive HPV test. In a woman with a normal Pap smear but positive high-risk HPV test, HPV genotyping should be considered. If HPV genotyping is not performed or it is not HPV 16/18, then the woman should return in a year to determine if the HPV infection is persistent. However, if the genotype is HPV 16/18, colposcopy should be considered. ASC-US with a negative HPV testing indicates only repeat testing in a year. A woman with ASC-US and a positive HPV test, LSIL, or HSIL should proceed to colposcopy. If the biopsy obtained during colposcopy is abnormal, further treatment is needed, which includes LEEP, cryotherapy, laser therapy, or cone biopsy.
6. HPV infection requires genital contact. Thus, abstinence or a monogamous relationship with an uninfected partner will prevent HPV infection. Condom use has been shown to reduce transmission, but it does not completely prevent infection. Two vaccines are available for the prevention of HPV infection. Both vaccines protect against HPV 16 and 18 which together cause ~70% of cervical and anal cancers. One of the vaccines also prevents infection with HPV types 6 and 11, which cause ~90% of genital warts. The quadrivalent vaccine requires three injections over 6 months and is approved for females and males aged 9 to 26. Likewise, the bivalent vaccine requires three injections over 6 months, but is approved only for females aged 9 to 25. Neither vaccine has been shown to provide protection against other high-risk HPV types, which is why vaccinated women should continue to get routine cervical cancer screening by Pap smear and HPV molecular detection.
The HPV vaccines are composed of HPV surface components that aggregate to form virus-like particles (VLPs). These VLPs contain no DNA, so there is no risk of developing HPV infection from vaccination. However, the VLPs stimulate antibody production, which protects the host against future HPV infections with the specific HPV types in the vaccine. Longitudinal outcome studies are still being performed on these relatively new vaccines, but the data to date indicate nearly 100% protection from persistent HPV 16/18 infections and the associated precancerous changes up to 8 years post-vaccination. HPV vaccination is recommended for 11- to 12-year-old girls and boys. In addition, females aged 13 to 26 and males aged 13 to 21 should receive the vaccine series if not previously vaccinated. Men who have sex with men should receive the vaccine through 26 years of age.
REFERENCES
1. Burd EM. 2003. Human papillomavirus and cervical cancer. Clin Microbiol Rev 16:1–17.
2. Committee on Practice Bulletins—Gynecology. 2012. ACOG Practice Bulletin No. 131: Screening for cervical cancer. Obstet Gynecol 120:1222–1238.
3. Mayrand MH, Duarte-Franco E, Rodrigues I, Walter SD, Hanley J, Ferenczy A, Ratnam S, Coutlée F, Franco EL; Canadian Cervical Cancer Screening Trial Study Group. 2007. Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Engl J Med 357:1579–1588.
4. Moyer VA; U.S. Preventative Services Task Force. 2012. Screening for cervical cancer: U.S. Preventative Services Task Force Recommendation Statement. Ann Intern Med 156:880–891.
5. Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J, Garcia FA, Moriarty AT, Waxman AG, Wilbur DC, Wentzensen N, Downs LS Jr, Spitzer M, Moscicki AB, Franco EL, Stoler MH, Schiffman M, Castle PE, Myers ER; ACS-ASCCP-ASCP Cervical Cancer Guideline Committee. 2012. American Cancer Society, American Society for Coloposcopy and Cervical Pathology, and American Society for Clinical Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer. CA Cancer J Clin 62:147–172.
6. Workowski KA, Berman S; Centers for Disease Control and Prevention. 2010. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep 59:1–110.
SECTION TWO
RESPIRATORY TRACT INFECTIONS
INTRODUCTION TO SECTION II
Respiratory tract infections are a major reason why children and the elderly seek medical care. These infections are more common in cold-weather months in locales with temperate climates. Respiratory tract infections are primarily spread by inhalation of aerosolized respiratory secretions from infected hosts. Some respiratory tract pathogens, such as rhinoviruses and respiratory