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Long-term outcomes of high-risk human papillomavirus infection support a long interval of cervical cancer screening.

Huang YK, You SL, Yuan CC, Ke YM, Cao JM, Liao CY, Wu CH, Hsu CS, Huang KF, Lu CH, Twu NF, Chu TY - Br. J. Cancer (2008)

Bottom Line: The cumulative incidences of high-grade squamous intraepithelial lesion (HSIL) and in situ/invasive cancer in HPV-positive women were 5.6 and 3.7%, respectively, and those in HPV-negative women were 0.3 and 0%.After adjusting for other risk factors, HPV-positive subjects had 24.9 (95% CI: 7.0-108.3; P<0.0001) folds of risk of developing HSIL or above cervical neoplasia as compared to HPV-negative subjects, whereas risk for low-grade intraepithelial lesion and atypical squamous cytology was not increased.The result supports an HPV test-orientated CC screening programme with intervals of at least 5 years.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan, ROC.

ABSTRACT
Knowing that infection of high-risk human papillomavirus (HPV) causes virtually all cervical cancer (CC), the long-term outcomes of HPV infection, especially the absolute risk and time lapse of developing CC, are beyond the scope of ordinary follow-up study owing to ethical concerns. The present study followed the natural history and long-term outcomes of HPV infection in a cohort of women by national health insurance care and data linkage without additional disturbance. The status of cervical HPV infection was determined in 1708 healthy women, aged 20-90 (median 43), enrolled from 10 hospitals in seven cities around the island country of Taiwan. Records of consecutive Pap smear results and cancer reports of 108 cytology-negative, HPV-positive and 1202 cytology- and HPV-negative women with no prior record of CC or abnormal cervical cytology were retrospectively analysed for a duration of up to 75 months (median 61 months). The cumulative incidences of high-grade squamous intraepithelial lesion (HSIL) and in situ/invasive cancer in HPV-positive women were 5.6 and 3.7%, respectively, and those in HPV-negative women were 0.3 and 0%. After adjusting for other risk factors, HPV-positive subjects had 24.9 (95% CI: 7.0-108.3; P<0.0001) folds of risk of developing HSIL or above cervical neoplasia as compared to HPV-negative subjects, whereas risk for low-grade intraepithelial lesion and atypical squamous cytology was not increased. The study showed that women with a prevalent infection of high-risk HPV had a 4% cumulative risk for CC in 6 years, whereas those tested negative had little risk. The result supports an HPV test-orientated CC screening programme with intervals of at least 5 years.

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Kaplan–Meier estimates of HSIL or above outcome in HPV-positive and HPV-negative subjects. Failure was defined as the occurrence of HSIL or above cervical neoplasia. The adjusted hazard ratio was 24.9 (7.01–108.27) (P<0.0001). HPV=human papillomavirus; HSIL=high-grade squamous intraepithelial lesion.
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fig3: Kaplan–Meier estimates of HSIL or above outcome in HPV-positive and HPV-negative subjects. Failure was defined as the occurrence of HSIL or above cervical neoplasia. The adjusted hazard ratio was 24.9 (7.01–108.27) (P<0.0001). HPV=human papillomavirus; HSIL=high-grade squamous intraepithelial lesion.

Mentions: The records of consecutive Pap smear results and cancer reports of 108 cytology-negative, HPV-positive and 1202 cytology- and HPV-negative women were followed for a median duration of 61 months. In the meanwhile, there were five prevalent cases of CC, who were all HPV-positive, being excluded from the follow-up. The status of HPV infection on enrolment mattered greatly to the outcomes of follow-up. In HPV-positive subjects (n=108), 12% developed cervical neoplasia, whereas only 3.8% of HPV-negative subjects (n=1202) did so. The major difference was the occurrence rate of HSIL or above neoplasia, which was 9.25% in the HPV-positive group and 0.14% in the HPV-negative group. All the four subjects with follow-up outcomes of CIS (n=2), AIS or CC were HPV-positive on enrolment (Table 3). When comparing different follow-up outcomes, the HPV prevalence at enrolment was significantly higher in the CIS/AIS/CC outcome group (100%) than in the HSIL outcome (60.0%), Atypia outcome (9.4%), Normal outcome (7.6%) and LSIL outcome (0%) groups (P<0.0001, Table 3). As shown in Figure 3, during a maximal follow-up of 74 months, the occurrence of HSIL or above cervical neoplasia was significantly higher in the HPV-positive subjects than in the HPV-negative subjects, with an adjusted hazard ratio of 24.9 (7.01–108.27) (P<0.0001). Table 4 summarises the incidence and hazard ratio of different follow-up outcomes. Compared to HPV-negative subjects, the incidence of HSIL or above neoplasia in HPV-positive subjects was significantly higher (0.0194 vs 0.0007), but this was not true in the Atypia and LSIL groups.


Long-term outcomes of high-risk human papillomavirus infection support a long interval of cervical cancer screening.

Huang YK, You SL, Yuan CC, Ke YM, Cao JM, Liao CY, Wu CH, Hsu CS, Huang KF, Lu CH, Twu NF, Chu TY - Br. J. Cancer (2008)

Kaplan–Meier estimates of HSIL or above outcome in HPV-positive and HPV-negative subjects. Failure was defined as the occurrence of HSIL or above cervical neoplasia. The adjusted hazard ratio was 24.9 (7.01–108.27) (P<0.0001). HPV=human papillomavirus; HSIL=high-grade squamous intraepithelial lesion.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2266853&req=5

fig3: Kaplan–Meier estimates of HSIL or above outcome in HPV-positive and HPV-negative subjects. Failure was defined as the occurrence of HSIL or above cervical neoplasia. The adjusted hazard ratio was 24.9 (7.01–108.27) (P<0.0001). HPV=human papillomavirus; HSIL=high-grade squamous intraepithelial lesion.
Mentions: The records of consecutive Pap smear results and cancer reports of 108 cytology-negative, HPV-positive and 1202 cytology- and HPV-negative women were followed for a median duration of 61 months. In the meanwhile, there were five prevalent cases of CC, who were all HPV-positive, being excluded from the follow-up. The status of HPV infection on enrolment mattered greatly to the outcomes of follow-up. In HPV-positive subjects (n=108), 12% developed cervical neoplasia, whereas only 3.8% of HPV-negative subjects (n=1202) did so. The major difference was the occurrence rate of HSIL or above neoplasia, which was 9.25% in the HPV-positive group and 0.14% in the HPV-negative group. All the four subjects with follow-up outcomes of CIS (n=2), AIS or CC were HPV-positive on enrolment (Table 3). When comparing different follow-up outcomes, the HPV prevalence at enrolment was significantly higher in the CIS/AIS/CC outcome group (100%) than in the HSIL outcome (60.0%), Atypia outcome (9.4%), Normal outcome (7.6%) and LSIL outcome (0%) groups (P<0.0001, Table 3). As shown in Figure 3, during a maximal follow-up of 74 months, the occurrence of HSIL or above cervical neoplasia was significantly higher in the HPV-positive subjects than in the HPV-negative subjects, with an adjusted hazard ratio of 24.9 (7.01–108.27) (P<0.0001). Table 4 summarises the incidence and hazard ratio of different follow-up outcomes. Compared to HPV-negative subjects, the incidence of HSIL or above neoplasia in HPV-positive subjects was significantly higher (0.0194 vs 0.0007), but this was not true in the Atypia and LSIL groups.

Bottom Line: The cumulative incidences of high-grade squamous intraepithelial lesion (HSIL) and in situ/invasive cancer in HPV-positive women were 5.6 and 3.7%, respectively, and those in HPV-negative women were 0.3 and 0%.After adjusting for other risk factors, HPV-positive subjects had 24.9 (95% CI: 7.0-108.3; P<0.0001) folds of risk of developing HSIL or above cervical neoplasia as compared to HPV-negative subjects, whereas risk for low-grade intraepithelial lesion and atypical squamous cytology was not increased.The result supports an HPV test-orientated CC screening programme with intervals of at least 5 years.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan, ROC.

ABSTRACT
Knowing that infection of high-risk human papillomavirus (HPV) causes virtually all cervical cancer (CC), the long-term outcomes of HPV infection, especially the absolute risk and time lapse of developing CC, are beyond the scope of ordinary follow-up study owing to ethical concerns. The present study followed the natural history and long-term outcomes of HPV infection in a cohort of women by national health insurance care and data linkage without additional disturbance. The status of cervical HPV infection was determined in 1708 healthy women, aged 20-90 (median 43), enrolled from 10 hospitals in seven cities around the island country of Taiwan. Records of consecutive Pap smear results and cancer reports of 108 cytology-negative, HPV-positive and 1202 cytology- and HPV-negative women with no prior record of CC or abnormal cervical cytology were retrospectively analysed for a duration of up to 75 months (median 61 months). The cumulative incidences of high-grade squamous intraepithelial lesion (HSIL) and in situ/invasive cancer in HPV-positive women were 5.6 and 3.7%, respectively, and those in HPV-negative women were 0.3 and 0%. After adjusting for other risk factors, HPV-positive subjects had 24.9 (95% CI: 7.0-108.3; P<0.0001) folds of risk of developing HSIL or above cervical neoplasia as compared to HPV-negative subjects, whereas risk for low-grade intraepithelial lesion and atypical squamous cytology was not increased. The study showed that women with a prevalent infection of high-risk HPV had a 4% cumulative risk for CC in 6 years, whereas those tested negative had little risk. The result supports an HPV test-orientated CC screening programme with intervals of at least 5 years.

Show MeSH
Related in: MedlinePlus