The Role of Human Papilloma Virus Testing in Cervical Cancer Prevention

Molly C. Fey, FNP, MSN; Margaret W. Beal, CNM, PhD

Disclosures

J Midwifery Womens Health. 2004;49(1) 

In This Article

HPV Infection

Almost all strains of HPV that infect the anogenital tract are capable of causing abnormal cervical cytology.[11,22,23] A clear causal relationship has been established between HPV infection and cervical cancer, and HPV is found in nearly 100% of cervical malignancies worldwide.[2,24] This link is the highest attributable fraction ever identified for a specific cause of a major human cancer worldwide.[22,24] The latency period between initial HPV exposure and development of cervical cancer may be months to years. Although rapid progression is possible, average time from initial infection to manifestation of invasive cervical cancer is estimated at up to 15 years.[9]

Genital HPV strains are divided into two groups, based on their oncogenic potential and ability to induce viral-associated tumors. Certain strains termed "high-risk strains" (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) are associated with intraepithelial neoplasia and are more likely to progress to severe lesions and cancer.[25] Of these, HPV 16 and 18 are the most carcinogenic and most prevalent.[3,8,22] HPV 16 is the predominant strain in almost all regions of the world, with the exception of Southeast Asia, where HPV 18 has the highest prevalence.[12,22] HPV 16 alone accounts for more than 50% of HPV infections, and it is estimated that almost 20% of American women are infected.[8,22,26] High-grade cervical intraepithelial lesions are most commonly associated with HPV 16 and 18, yet these strains are also frequently found to be the etiologic factor in minor lesions and mild dysplasia.[3]

Low-risk strains (HPV 6, 11, 42, 43, and 44) are associated with condylomata and low-grade cervical changes, such as mild dysplasia.[2,11] Lesions due to low-risk HPV infection have a high likelihood of regression, little potential for progression, and are considered of no or low oncogenic risk.[2,5] It is hypothesized that the different high- and low-risk HPV strains exert varying degrees of transmissibility, yet no clear data exist to define this parameter of infection.[7]

Prevalence of HPV is greatest in young, sexually active individuals. For women, prevalence peaks in the 20- to 24-year-old age group, with estimates as high as 50%. The 15- to 19-year-old age group has the next highest rates of HPV infection. Prevalence then decreases with age, dropping sharply in women over 30. This decrease is most likely due to fewer sexual partners and decreased exposure, in addition to maturational protection as ectopy decreases and the vulnerable transformation zone regresses with aging.[3,7,8]

Despite the significant correlation between high-risk HPV and cervical cancer, 80% of infections are transient, asymptomatic, and resolve without treatment (Figure 1).[5,27] When this occurs, HPV-related cervical intraepithelial lesions spontaneously regress, and HPV is no longer detectable in the cervix. Lesion clearance and reversion to a negative HPV test result is mediated by both the oncogenic risk potential of the viral strain and host immunologic factors. Spontaneous regression of HPV-related cervical lesions generally occurs if the premalignant abnormalities are at or below the level of low-grade changes. Rates of regression diminish with increased severity of the lesion.[3,5,28] Median duration of locally detectable HPV infection ranges from 6 to 14 months.[5,29] Within 2 to 4 years, only 15% to 25% of low-grade cervical intraepithelial lesions progress to high-grade severity.[7,29] Persistent high-risk HPV infection is the key attribute of high-grade cervical disease.[2,23,29]

Figure 1.

Natural history of HPV infection. *Average time from infection to invasive cervical cancer is 15 years. HPV clearance is mediated by immune status and infection cofactors.

HPV in adolescents is frequently short-lived and spontaneously regressive, whereas infection in older women tends to persist.[29,30,31,32] The correlation between age and clearance versus persistence is not fully understood. Immune and/or hormonal changes in older women may impair clearance of the virus and favor HPV-related cytologic changes, or these infections may have been acquired at a young age and have persisted into older age.[7,30]

Systemic responses to HPV infection in immunocompetent individuals are varied and currently under investigation.[33,34,35] Preliminary research indicates that many women clear HPV serologically via antibody response and acquire protective immunity to specific viral strains. For others, the infection may be eliminated locally without systemic detection or immune effects.[33,34,35] Local and systemic immune response to HPV, as well as mechanisms of viral clearance and lesion regression, demand further research.

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