Cervical cancer mortality in Chile is four times higher than in developed countries. We compared the accuracy of human papillomavirus (HPV) DNA testing and conventional Papanicolaou (Pap) testing to detect prevalent precancerous and cancerous lesions in the routine clinical practice of the public health system. Women aged 25 years and older residing in the area covered by three primary care centers of Santiago, Chile, were invited to participate. Eligible women received both HPV DNA (Hybrid Capture 2) and Pap testing. Women positive by either test (Pap: ASCUS1, HC2: RLU/CO !1.0) underwent colposcopy and biopsy, as did a sample of double-negative women with an abnormal cervix at visual inspection or with risk factors for cervical lesions. Crude and verification bias-corrected sensitivities and specificities were estimated. In total, 8,265 women (98.8% of eligible) had complete screening results. Of these, 10.7% were HPV positive, 1.7% were Pap positive and 1.1% were positive by both tests. In all, 931 (11.3%) women were screen-positive, of whom 94.3% attended colposcopy. Additionally, 295 control women were invited for colposcopy, of whom 78% attended. In all, 42 CIN2, 45 CIN3 and 9 cancers were identified. Verification bias-corrected sensitivity for CIN21 (95% confidence interval) was 92.7% (84.4-96.8) for HPV and 22.1% (16.4-29.2) for Pap; corresponding specificities were 92.0% (91.4-92.6) and 98.9% (98.7-99.0). In conclusion, in routine clinical practice in a developing country, HPV testing was four times more sensitive for CIN21 than Pap testing, identifying three times more CIN21 lesions; HPV testing was easily implemented in our established cervical cancer prevention program.In Chile, cervical cancer causes the death of more than 600 women each year, mainly of low socio-economic level, and is the second most common cause of cancer death for Chilean women aged 20-44 years.1 The current country's mortality rate of 7.6/100,000 is four times higher than that of developed countries.2,3 These facts emphasize the need to improve the effectiveness and equitability of the national cervical cancer prevention program.There is ample evidence that the detection of human papillomavirus (HPV) DNA in cervical samples has a higher sensitivity for cervical cancer and precancerous lesions than the Papanicolaou (Pap) test, 4 and high-quality HPV tests are routinely used in prevention programs in some developed countries. Although there have been many studies of implementing de novo screening methods in developing countries, [5][6][7][8]

BackgroundWe previously conducted a population-based screening trial of high-risk human papillomavirus (hrHPV) testing and conventional cytology, demonstrating higher sensitivity (92.7 % vs 22.1 % for CIN2+) but lower positive predictive value (10.5 % vs 23.9 %) of hrHPV testing. Here we report the performance of HPV16/18 genotyping to triage the hrHPV positive participants.MethodsWomen aged 25 years and older received hrHPV (Hybrid Capture 2) and Papanicolaou testing; positives by either test underwent colposcopy and directed biopsy, as did a sample of double-negatives. hrHPV positive women were reflex-tested with HPV16/18 genotyping (Digene HPV Genotyping PS Test).ResultsAmong the 8,265 participants, 10.7 % were hrHPV positive, 1.7 % had ASCUS+ cytology, 1.2 % had CIN2+; 776 (88 %) hrHPV positive women had complete results, of whom 38.8 % were positive for HPV16 (24.0 %), HPV18 (9.7 %) or both (5.1 %). CIN2+ prevalence in HPV16/18 positive women (16.3 %, 95 % CI 12.3-20.9) was twice that of HPV16/18 negative women (8.0 %, 95 % CI 5.7-10.8). HPV16/18 genotyping identified 40.5 % of CIN2, 66.7 % of CIN3 and 75.0 % of cancers. Compared to hrHPV screening alone, HPV16/18 triage significantly reduced the referral rate (10.7 % vs 3.7 %) and the number of colposcopies required to detect one CIN2+ (9 vs 6). When HPV16/18 negative women with baseline ASCUS+ cytology were also colposcopied, an additional 14 % of CIN2+ was identified; referral increased slightly to 4.2 %.ConclusionsHPV16/18 triage effectively stratified hrHPV positive women by their risk of high-grade lesions. HPV16/18 positive women must be referred immediately; referral could be deferred in HPV16/18 negative women given the slower progression of non-HPV16/18 lesions, however, they will require active follow-up.

BackgroundThe need to review cervical cancer prevention strategies has been triggered by the availability of new prevention tools linked to human papillomavirus (HPV): vaccines and screening tests. To consider these innovations, information on HPV type distribution and natural history is necessary. This is a five-year follow-up study of gynecological high-risk (HR) HPV infection among a Chilean population-based cohort of women.FindingsA population-based random sample of 969 women from Santiago, Chile aged 17 years or older was enrolled in 2001 and revisited in 2006. At both visits they answered a survey on demographics and sexual history and provided a cervical sample for HPV DNA detection (GP5+/6+ primer-mediated PCR and Reverse line blot genotyping). Follow-up was completed by 576 (59.4%) women; 45 (4.6%) refused participation; most losses to follow-up were women who were unreachable, no longer eligible or had missing samples. HR-HPV prevalence increased by 43%. Incidence was highest in women < 20 years of age (19.4%) and lowest in women > 70 (0%); it was three times higher among women HR-HPV positive versus HPV negative at baseline (25.5% and 8.3%; OR 3.8, 95% CI 1.8-8.0). Type-specific persistence was 35.3%; it increased with age, from 0% in women < 30 years of age to 100% in women > 70. An enrollment Pap result ASCUS or worse was the only risk factor for being HR-HPV positive at both visits.ConclusionsHR-HPV prevalence increased in the study population. All HR-HPV infections in women < 30 years old cleared, supporting the current recommendation of HR-HPV screening for women > 30 years.

BackgroundHuman papillomavirus (HPV) serology is a main factor for designing vaccination programs and surveillance strategies; nevertheless, there are few reports of HPV seroprevalence in the general population, especially in Latin America. This study aimed to describe high-risk HPV serological prevalence, persistence, and association with concurrent cervical infection, in Chilean women.Methods1021 women from the general population, aged 15–85 years, were studied in 2001 of whom 600 were reexamined in 2006. The assessments at both time points included cervical HPV DNA testing, HPV antibody testing, cervical cytology and a sociodemographic/behavioral questionnaire. HPV DNA and antibodies against L1 protein of types 16, 18, 31, 33, 35, 45, 52, and 58 were assessed by reverse line blot and multiplex serology, respectively.ResultsSeropositivity was high at both baseline (43.2%) and follow-up (50.2%) and increased with age (p < 0.001); corresponding DNA prevalences were 6.7% and 8.7%. DNA and seroprevalence were associated at baseline (p = 0.01 for any HPV). Early age at first sexual intercourse and having had two or more sexual partners were independently associated with seropositivity. Most (82.0%) initially seropositive women remained seropositive at follow-up; 21.6% of initially seronegative women seroconverted, reaching 17.5% among women older than 60 years of age. ASCUS or worse cytology was correlated with HPV DNA positivity but not with HPV seropositivity.ConclusionHPV seroprevalence studies are a useful tool for learning about the dynamics of HPV infection in a community. This study contributes to understanding the natural history of HPV infection and provides a baseline assessment before the incorporation of HPV vaccination into a national program.

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