HPV Screening for Cervical Cancer in Rural India

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n engl j med 360;14 nejm.org april 2, 2009 1385

Thenew englandjournalofmedicineestablished in 1812 april 2, 2009 vol. 360 no. 14

HPV Screening for Cervical Cancer in Rural India

Rengaswamy Sankaranarayanan, M.D., Bhagwan M. Nene, M.D., F.R.C.P., Surendra S. Shastri, M.D.,Kasturi Jayant, M.Sc., Richard Muwonge, Ph.D., Atul M. Budukh, Ph.D., Sanjay Hingmire, B.Sc.,

Sylla G. Malvi, M.Sc., Ph.D., Ranjit Thorat, B.Sc., Ashok Kothari, M.D., Roshan Chinoy, M.D., Rohini Kelkar, M.D.,Shubhada Kane, M.D., Sangeetha Desai, M.D., Vijay R. Keskar, M.S., Raghevendra Rajeshwarkar, M.D.,

Nandkumar Panse, B.Com., and Ketayun A. Dinshaw, M.D., F.R.C.R.

A b s t ra c t

From the International Agency for Re-search on Cancer, Lyon, France (R.S.,R.M.); and the Nargis Dutt MemorialCancer Hospital, Tata Memorial CentreRural Cancer Project, Barshi (B.M.N., K.J.,A.M.B., S.H., S.G.M., R.T., A.K., V.R.K.,R.R., N.P.), and the Tata Memorial Cen-tre, Mumbai (S.S.S., R.C., R.K., S.K., S.D.,K.A.D.) both in India. Address reprintrequests to Dr. Sankaranarayanan at theInternational Agency for Research on Can-

cer, 150 cours Albert Thomas, Lyon 69008,France, or at [email protected].

N Engl J Med 2009;360:1385-94.Copyright 2009 Massachusetts Medical Society.

Background

In October 1999, we began to measure the effect of a single round of screening bytesting for human papillomavirus (HPV), cytologic testing, or visual inspection ofthe cervix with acetic acid (VIA) on the incidence of cervical cancer and the associ-ated rates of death in the Osmanabad district in India.

Methods

In this cluster-randomized trial, 52 clusters of villages, with a total of 131,746 healthywomen between the ages of 30 and 59 years, were randomly assigned to four groupsof 13 clusters each. The groups were randomly assigned to undergo screening byHPV testing (34,126 women), cytologic testing (32,058), or VIA (34,074) or to receivestandard care (31,488, control group). Women who had positive results on screen-ing underwent colposcopy and directed biopsies, and those with cervical precancer-ous lesions or cancer received appropriate treatment.

Results

In the HPV-testing group, cervical cancer was diagnosed in 127 subjects (of whom39 had stage II or higher), as compared with 118 subjects (of whom 82 had advanceddisease) in the control group (hazard ratio for the detection of advanced cancer inthe HPV-testing group, 0.47; 95% confidence interval [CI], 0.32 to 0.69). There were34 deaths from cancer in the HPV-testing group, as compared with 64 in the control

group (hazard ratio, 0.52; 95% CI, 0.33 to 0.83). No significant reductions in thenumbers of advanced cancers or deaths were observed in the cytologic-testing groupor in the VIA group, as compared with the control group. Mild adverse events werereported in 0.1% of screened women.

Conclusions

In a low-resource setting, a single round of HPV testing was associated with a sig-nificant reduction in the numbers of advanced cervical cancers and deaths fromcervical cancer.

The New England Journal of Medicine

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Th e n e w e n g l a n d j o u r n a l o f medicine

n engl j med 360;14 nejm.org april 2, 20091386

In developing countries, there is alack of effective screening programs for cer-vical cancer. In these countries, no clinically

significant reduction in the incidence of cervicalcancer has occurred during the past three de-cades.1-4In developed countries, by contrast, therehas been a major decline in cervical-cancer mor-

tality after the introduction of large-scale cytologictesting. The limited success of such screening indeveloping countries has stimulated evaluation oftesting for human papillomavirus (HPV) and visualinspection of the cervix with acetic acid (VIA).

In October 1999, we initiated a cluster-random-ized, controlled trial to evaluate the effectivenessof a single round of HPV testing, cytologic test-ing, or VIA in reducing the incidence of cervicalcancer, as compared with a control group that re-ceived usual care in a previously unscreened, high-risk population in the Osmanabad district in the

state of Maharashtra, India.5We report the cervi-cal-cancer incidence and mortality in the fourgroups after 8 years of follow-up.

Methods

Study Design

The study design and methods have been describedin detail previously.5The scientific and ethical re-view committees of the International Agency forResearch on Cancer (IARC) and the Tata MemorialCentre (TMC) and the Nargis Dutt Memorial Can-cer Hospital (NDMCH) reviewed and approved theprotocol. Clusters of villages consisting of a totalof 497 villages in the Osmanabad district that hada primary health care center constituted the ran-domization unit. A statistician at the IARC whowas not involved in the project randomly assigned52 such clusters to four groups consisting of 13clusters each. The groups were randomly assignedto receive screening by HPV testing, cytologic test-ing, or VIA or to receive standard care (controlgroup). Although both practitioners and subjects

were aware of study-group assignments, the blind-ed outcome assessment was performed by cancer-registry personnel in the Osmanabad district. Thestudy was initiated in January 2000, and the re-sults reported here are based on follow-up throughDecember 31, 2007. The study was supported bythe Bill and Melinda Gates Foundation throughthe Alliance for Cervical Cancer Prevention.

Subjects

Eligible women were between the ages of 30 and59 years, were healthy, were currently or had beenmarried, and were not pregnant. All the womenhad an intact uterus with no prolapse, had no his-tory of cervical cancer, and were living in the studyclusters. The women were identified with the use

of household surveys. After explaining the studyand obtaining written informed consent, femalehealth workers interviewed the women in each ofthe four study groups with respect to sociodemo-graphic and reproductive characteristics, using astructured questionnaire. They also instructed allthe women about the causes of cervical cancer,signs and symptoms, prevention, early detection,and treatment.

Women in the 13 control clusters were not of-fered screening but were advised on how to seekscreening at local hospitals. Women in the clusters

who were assigned to screening were given a cardindicating the date, time, and place of screening.

Training

Screening was performed by nine auxiliary nursemidwives who were trained in a 3-week coursewith the use of IARC manuals in the collection ofcervical cells for HPV testing and cytologic test-ing and in performing VIA and cryotherapy.6,7Ninedoctors were trained to supervise the auxiliarynursemidwives and to perform colposcopy, cryo-therapy, and the loop electrosurgical excision pro-cedure (LEEP).5,7Two pathologists reviewed thereporting of cervical neoplasms at the TMC. Thetechnicians who were responsible for processingand reading Papanicolaou smears, processing bi-opsy specimens, and testing for HPV using theHybrid Capture II test (Qiagen) were trained for3 months at the TMC.

Screening, Diagnosis, and Treatment

Women were screened in village clinics that wereorganized in local primary health centers, munici-

pal off ices, or schools. The screening process, in-vestigations, and treatments were explained to thewomen.

In the HPV-testing group, cervical samples, col-lected in a special transport medium, were pro-cessed with the use of the Hybrid Capture II assayfor 13 high-risk HPV types (16, 18, 31, 33, 35, 39,45, 51, 52, 56, 58, 59, and 68) on the basis of the





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manufacturers instructions. A positive result wasrecorded for specimens with a ratio of the rela-tive light unit to a positive control (RLU/PC) of1 or more, corresponding to 5000 or more viralcopies. In the cytologic-testing group, cervical cellswere collected with the use of Cervex brushes, andthe smears were processed at NDMCH and re-

ported according to the 1991 Bethesda system.8Results for women with atypical squamous cellsof uncertain significance or higher-grade lesionswere defined as positive. In the VIA group, womenwith well-defined, dense aceto-white lesions in thecervix, close to the squamocolumnar junction orthe os, or aceto-whitening of a cervical growth1 minute after the application of 4% acetic acidwere categorized as VIA-positive.5,6Subjects in thisgroup underwent immediate colposcopy and di-rected biopsies from abnormal areas by a physi-cian in the field clinic and were given appoint-

ments for treatment at the NDMCH. Results ofHPV testing or cytologic testing were deliveredto the subjects within 2 weeks after testing, andthose with positive tests were given appointmentsfor colposcopy, biopsy, and treatment.

Women with a positive screening test wereevaluated by means of colposcopy, and doctorsreported the results as normal f indings, inflam-mation, probable low-grade or high-grade precan-cerous lesions, or invasive cancer.7The colposcopicfindings were explained to the women, and punch-biopsy specimens were obtained from abnormalareas. Biopsy specimens were processed at theNDMCH and reported according to typical termi-nology regarding cervical intraepithelial neoplasia(CIN) grade.9Women with colposcopic findingsof low-grade or high-grade lesions were offeredimmediate cryotherapy after the directed biopsy,if all the following criteria were met: the lesioncould be covered by the cryoprobe and involvedthree quadrants or less of the cervix with no ex-tension into the endocervix or vaginal walls, thesquamocolumnar junction was fully visible, and

there was no suspicion of invasive cancer. LEEP orconization was offered to women with CIN lesionsthat were unsuitable for cryotherapy. Women withCIN grade 2 or 3 lesions were brought back forcryotherapy or LEEP. Women with suspected in-vasive cancer were referred to the NDMCH or tothe hospital of their choice for investigations andtreatment with surgery, radiotherapy, or both.

Quality Assurance

Provider competency was maintained by medicalsupervision in the field and by periodic refreshercourses to monitor their performance, along withrates of positive results on screening, correlationbetween colposcopy and histologic findings, andpositive predictive values for CIN.5Internal and

external quality-control measures were in place forcolposcopy and pathological analysis.5

Outcome Measures

The primary outcomes were the incidence of cer-vical cancer and associated rates of death. Second-ary outcomes included stage distribution accord-ing to the International Federation of Gynecologyand Obstetrics (FIGO) staging system10and sur-vival and case fatality rates. Cancer-registry staffmembers who were unaware of study-group as-signments collected data on the date of diagnosis,

stage, treatment, and follow-up details for subjectswith cervical cancer, using active case-f indingmethods.11Information on all deaths among thesubjects was collected from the district death-registration offices, hospital records, and annualhouse visits. The cause of death for each subjectwith cervical cancer in the district was assessedby the cancer-registry staff after evaluation of datafrom hospital records, death certif icates, house vis-its, and interviews of relatives or friends. Thescreening-project staff then matched the subjectswho had incident cervical cancer and those whodied with the study database.

Statistical Analysis

The study was designed to have a power of 80%to detect a 50% reduction in the cumulative rateof death from cervical cancer within 15 years af-ter enrollment in one of the intervention groups,as compared with the control group. The deathrate from cervical cancer in women between theages of 30 and 59 years was assumed to be around20 per 100,000. We assumed that clusters consist-

ing of an average of 2500 women would provideabout 25,600 person-years of observation after 15years (assuming a yearly dropout rate of 2.5%).Taking into account the effect of the intraclustercorrelation, we assumed a coefficient variation of0.3 in other words, the true rates of death fromcervical cancer in the control group would vary be-tween 8 and 32 per 100,000. Since this assump-





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tion led to a design effect of 1.38, we needed torandomize at least 13 clusters in each study group.12The sample-size requirement was satisfied, sinceeach group involved 13 clusters of an average of2744 women. A P value of less than 0.05 was con-sidered to indicate statistical significance.

Data were entered in an ACCESS database and

analyzed with the use of a Stata software pack-age, version 10.0. Analysis was performed accord-ing to the intention-to-treat principle: all eligiblewomen in the randomized clusters were included,regardless of their participation in interviews orscreening visits. Since the trial used a cluster de-sign, analyses of household and individual char-acteristics were performed with the use of thecluster as the unit of analysis. Comparisons ofcluster proportions or means of household andindividual characteristics within the four study

groups were performed with the use of theKruskalWallis rank test. Multivariate analysis ofthe primary outcomes of cervical-cancer incidenceand associated mortality was performed with theuse of Cox proportional-hazards regression, takinginto account the cluster design and with adjust-ment for age.

The subjects participation in screening andtreatment, rates of positivity on screening, posi-tive predictive values, CIN grades, and cancer-detection rates and stage distribution were calcu-lated as proportions. For the calculation of theincidence of cervical cancer, the numbers of per-son-years in the intervention groups and the con-trol group were estimated from the date of thestudy initiation (January 1, 2000) to the date ofdiagnosis, death, migration, or last follow-up visit,whichever occurred f irst; for rates of death, the

52 Clusters underwentrandomization

52 Clusters were assessedfor eligibility

0 Were excluded

13 Clusters were included inintention-to-treat analysis

Median cluster size, 2316Range, 2009392134,074 Eligible women

0 Clusters were excludedfrom analysis

13 Subjects were identifiedbut died or migratedbefore study began





0 Clusters were

lost to follow-up;6934 eligible

women (20.3%)were not screened

0 Clusters were



0 Clusters were







13 Clusters were assignedto control group

13 Received assignedroutine care


13 Clusters were assignedto HPV-testing group

13 Received assignedHPV testing


13 Clusters were assigned tocytologic-testing group

13 Received assignedcytologic testing


13 Clusters were assignedto VIA group

13 Received assigned VIAMedian cluster size, 2319Range, 2011392134,087 Eligible women

0 Clusters werelost to follow-up





l

Figure 1.Enrollment and Outcomes.

HPV denotes human papillomavirus, and VIA visual inspection of the cervix with acetic acid.





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number of person-years was calculated from thetime of study initiation to the date of death, mi-gration, or last follow-up visit, whichever occurredfirst. Data were censored on December 31, 2007.

Results

Subjects

Of the 131,806 eligible women, 60 died or mi-grated before the study began; thus, complete datawere available for 131,746 eligible women (Fig. 1).The study groups were equally distributed in termsof household type, religion, education, occupation,marital status, and number of pregnancies (Ta-ble 1). Only eight of the eligible women had un-dergone previous cervical screening.

Screening and Detection Rates of CIN

Screening was initiated in January 2000 and wascompleted by April 2003. Table 2lists the num-ber of invited and screened women, the numberand proportion of positive screen results, and thenumber of women detected with CIN and cervi-

cal cancer according to age. Of the 34,126 wom-en in the HPV-testing group, 27,192 (79.7%) werescreened and 2812 (10.3%) had positive results;of the 32,058 women in the cytologic-testinggroup, 25,549 (79.7%) were screened and 1787(7.0%) had positive results; and of the 34,074 wom-en in the VIA group, 26,765 (78.5%) were screenedand 3733 (13.9%) had positive results. More than88% of subjects with positive results underwentcolposcopy. The detection rate of CIN grade 1 was

Table 1.Baseline Characteristics of the Subjects.*

VariableHPV

TestingCytologicTesting VIA Control

PValue

Subjects no.

All 34,126 32,058 34,074 31,488

Range 19993549 17143315 20093921 11743168

Living in traditional home with thatched roof 0.77

Subjects no. 8089 10,291 10,082 8453

Average proportion in clusters % (range) 26 (472) 33 (387) 28 (183) 28 (


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higher in the VIA group than in either the HPV-testing group or the cytologic-testing group(P


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group, 1946 (6.2%) requested screening and weretested with cytologic testing; of these subjects,15 CIN grade 2 or 3 lesions were detected, and 41subjects had invasive cancer (18% in stage I and58% in stage III).

Cervical Cancer Incidence and Mortality

The numbers of cervical cancers that were detect-ed on screening (i.e., those that were diagnosedwithin 3 months after positive results) were 73 inthe HPV-testing group, 83 in the cytologic-testing

Table 3.Distribution of Clinical Stages and Rates of Death, According to Study Group (20002007).*

Stage at Diagnosis and Deathfrom Cervical Cancer HPV Testing

CytologicTesting VIA Control

no./total no. (%)

Subjects with positive screening results NA

Stage at diagnosis

IA 45/87 (51.7) 58/88 (65.9) 34/91 (37.4)

IB 25/87 (28.7) 20/88 (22.7) 19/91 (20.9)

II 14/87 (16.1) 10/88 (11.4) 35/91 (38.5)

Unknown 3/87 (3.4) 0 3/91 (3.3)

Death from cervical cancer 12/87 (13.8) 18/88 (20.5) 27/91 (29.7)

Subjects with negative screening results NA

Stage at diagnosis

IA 0 2/22 (9.1) 1/25 (4.0)

IB 2/8 (25.0) 4/22 (18.2) 4/25 (16.0)

II 5/8 (62.5) 15/22 (68.2) 19/25 (76.0)

Unknown 1/8 (12.5) 1/22 (4.5) 1/25 (4.0)

Death from cervical cancer 0 9/22 (40.9) 8/25 (32.0)

Subjects not screened NA

Stage at diagnosis

IA 2/32 (6.2) 0 0

IB 6/32 (18.8) 5/42 (11.9) 8/41 (19.5)

II 20/32 (62.5) 33/42 (78.6) 32/41 (78.0)

Unknown 4/32 (12.5) 4/42 (9.5) 1/41 (2.4)


All subjects assigned to undergo screening NA

Stage at diagnosis

IA 47/127 (37.0) 60/152 (39.5) 35/157 (22.3)

IB 33/127 (26.0) 29/152 (19.1) 31/157 (19.7)

II 39/127 (30.7) 58/152 (38.2) 86/157 (54.8)

Unknown 8/127 (6.3) 5/152 (3.3) 5/157 (3.2)


Subjects with symptoms at diagnosis NA NA NA

Stage at diagnosis

IA 7/118 (5.9)

IB 26/118 (22.0)

II 82/118 (69.5)Unknown 3/118 (2.5)

Death from cervical cancer 64/118 (54.2)

* HPV denotes human papillomavirus, NA not applicable, and VIA visual inspection of the cervix with acetic acid.





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group, and 82 in the VIA group. The numbers ofsubsequent incident cancers (i.e., those that werediagnosed 3 months after positive results onscreening or among women who had received neg-ative results) were 22 in the HPV-testing group, 27in the cytologic-testing group, and 34 in the VIAgroup. The proportions of cancers that were de-tected in stage I were about 60% in the HPV-test-ing and cytologic-testing groups, 42% in the VIAgroup, and 28% in the control group (Table 3).

There were 34 deaths from cervical cancer inthe HPV-testing group, 54 in the cytologic-testinggroup, 56 in the VIA group, and 64 in the controlgroup (Table 3). The incidence rate of cervicalcancer of stage II or higher and death rates fromcervical cancer were signif icantly higher in thecytologic-testing group and the VIA group thanin the HPV-testing group. In the HPV-testinggroup, the hazard ratio for the detection of ad-

vanced cancer was 0.47 (95% confidence interval[CI], 0.32 to 0.69) and the hazard ratio for deathwas 0.52 (95% CI, 0.33 to 0.83), as compared withthe control group (Table 4). During the 8-yearfollow-up period, invasive cervical cancer devel-oped in 8 of 24,380 HPV-negative women, in 22of 23,762 women who had negative results on cy-tologic testing, and in 25 of 23,032 women whohad negative results on VIA, with age-standard-ized rates of 3.7, 15.5, and 16.0 cases of invasive

cervical cancer per 100,000 person-years, respec-tively.

Figure 2shows the cumulative incidence ofcervical cancer, rates of stage II or higher disease,and cumulative mortality. The cumulative inci-dence of advanced cervical cancer and the cumu-lative rate of death were lower in the HPV-testinggroup than in the control group, and the gap wid-ened throughout the follow-up period. There wasno significant reduction in the rate of death fromany cause in the intervention groups, as comparedwith the control group (data not shown).

Among the women who were screened andtreated, mild adverse events were reported in 123women, and a severe adverse event of uncontrolledbleeding after LEEP that resulted in hysterectomywas reported in 1 woman.

Discussion

In our cluster-randomized, controlled trial, ascreening program for the detection of cervicalcancer was accomplished in a low-resource setting.Since there is little screening for cervical cancerin India, women who did not undergo screening(control group) were considered to receive the stan-dard of care. The inclusion of this control groupwas approved by the IARC and Indian institutionalethics committees.

Table 4.Incidence of Cervical Cancer and Rates of Death.*

Variable HPV Testing Cytologic Testing VIA Control

Incidence of all cervical cancer no. 127 152 157 118

Person-yr of follow-up no. 268,185 250,523 267,326 247,895

Rate per 100,000 person-yr 47.4 60.7 58.7 47.6

Hazard ratio (95% CI) 1.05 (0.771.43) 1.34 (0.991.82) 1.30 (0.951.78) 1.00Incidence of stage II or higher cervical cancer

no.39 58 86 82



Hazard ratio (95% CI) 0.47 (0.320.69) 0.75 (0.511.10) 1.04 (0.721.49) 1.00

Death no. 34 54 56 64



Hazard ratio (95% CI) 0.52 (0.330.83) 0.89 (0.621.27) 0.86 (0.601.25) 1.00

* Rates and hazard ratios have been adjusted for age. Hazard ratios are for the comparison between each interventiongroup and the control group. CI denotes confidence interval, HPV human papillomavirus, and VIA visual inspection ofthe cervix with acetic acid.





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The difference in the number of eligible wom-en that were reported previously5and the numberreported here was due to the erroneous inclusionof ineligible women in the original report andupdates of data. The randomization of groups ofwomen in clusters minimized the possibility thatthose assigned to one study group would receive

the intervention provided to another study group.Our study found that a single round of HPV

testing was associated with a significant declinein the rate of advanced cervical cancers and as-sociated deaths, as compared with the unscreenedcontrol group. By contrast, there was no signifi-cant reduction in the rate of death in either thecytologic-testing group or the VIA group, as com-pared with the control group. The age-standard-ized rate of invasive cancer among women whohad negative results on cytologic testing or VIAwas more than four times the rate among HPV-

negative women, indicating a high negative pre-dictive value associated with a negative HPV test.The reduction in the incidence of advanced can-cers and deaths associated with HPV testing prob-ably reflects the higher sensitivity of HPV testingto detect lesions with a high potential for malig-nant transformation than that of cytologic test-ing or VIA.

No reduction in the rate of cervical cancer wasobserved in the VIA group in our study, whereasthe procedure was associated with a 25% reduc-tion in cervical-cancer incidence and a 35% reduc-tion in mortality in a randomized trial in SouthIndia.13The reason for these differences in out-comes between the two studies is unknown butmay be due to the higher rate of treatment in theSouth Indian trial.

We found that HPV testing was the most ob-jective and reproducible of all cervical screeningtests and was less demanding in terms of train-ing and quality assurance. In low-resource settingswith no capacity for colposcopy and histopatho-logical analysis (e.g., many countries in sub-Saha-

ran Africa), HPV-positive women without clini-cal evidence of invasive cancer could receiveimmediate treatment, such as cryotherapy.14How-ever, since most HPV infect ions in young womenregress rapidly without causing clinically signifi-cant disease, such an approach raises a legitimateconcern. Hence, HPV testing should not be usedfor primary screening of women under 30 yearsof age.

A drawback to HPV testing is that it is moreexpensive ($20 to $30 per test, in U.S. dollars) and

time-consuming than other screening tests, andit requires a sophisticated laboratory infrastruc-ture. A simple, affordable, and accurate HPV test

5.0

Rate/1000Women

4.0

4.5

3.53.0

2.0

1.5

0.5

2.5

1.0

0.00 1 2 3 4 5 6 7 8

Year

B Cumulative Incidence of Stage II or Higher

A Cumulative Incidence

l

3.0

Rate/1000Women

2.0

1.5

0.5

2.5

1.0

0.00 1 2 3 4 5 6 7 8

Year

C Cumulative Mortality2.5

Rate/1000Women

1.5

2.0

1.0

0.5

0.00 1 2 3 4 5 6 7 8

Year

VIA Cytologictesting

HPV testing Control

Figure 2.Cumulative Incidence of Cervical Cancerof Any Stage (Panel A) and Stage II or Higher (Panel B)

and Cumulative Mortality (Panel C).

HPV denotes human papillomavirus, and VIA visual

inspection of the cervix with acetic acid.





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HPV Screening for Cervical Ca ncer in Rural India

(careHPV test, Qiagen) that provides results with-in 3 hours was evaluated in China, and its ac-curacy was similar to that of the Hybrid Capture IItest that we used in our study. The careHPV testhad higher sensitivity than VIA (90.2% vs. 41.4%)but a lower specificity (84.2% vs. 94.5%).15ThecareHPV test is expected to be commercially avail-

able in developing countries in the near future.Our results, combined with those of the Chinesestudy of the new HPV test, indicate that HPV test-ing is appropriate as a primary screening approachin low-resource settings for women who are atleast 30 years of age.15

Supported by the Bill and Melinda Gates Foundation, throughthe Alliance for Cervical Cancer Prevention.

No potential conflict of interest relevant to this article wasreported.

We thank the women who participated in this study and theirfamilies; the Ministry of Health, Government of Maharashtra;the Department of Atomic Energy, Government of India; theOsmanabad district collectors, Zilla Parishad chief executive of-

ficers, district health officers, and other administrative authori-ties; staff members of local health services, numerous womensorganizations, voluntary organizations, and civic leaders in theproject area who facilitated the conduct of the study; Dr. PeterBoyle, IARC director from 2004 through 2008; Dr. Ren Lam-bert, IARC visiting scientist; Dr. Catherine Sauvaget, IARC scien-tist; Drs. Stephen Duff y, Peter Sasieni, and Jack Cuzick of CancerResearch U.K., Wolfson Institute of Preventive Medicine, Lon-don, for their useful advice and comments on early versions of

the manuscript; Dr. D.M. Parkin of the Clinical Trial ServiceUnit and Epidemiological Studies Unit, University of Oxford,Oxford, United Kingdom, for his support and assistance in thedesign and the monitoring of the study and for his useful com-ments; Dr. John Sellors of the Program for Appropriate Technol-ogy in Health (PATH), Seattle; Drs. Ramani Wesley and Somana-than Thara of the Regional Cancer Centre, Trivandrum, India;Dr. Partha Basu of the Chittaranjan National Cancer Institute,Kolkata, India; Dr. Daniel Seigneurin of University Hospital,Grenoble, France; Dr. L. Frappart of the Edouard Herriot Hospi-tal and Dr. B. Fontanire of the Centre Leon Berard (both inLyon, France) for their assistance in training and qualit y controlof various study inputs; our colleagues in TMC, NDMCH, andIARC who helped us in several project-related inputs; and Mrs.Evelyn Bayle of the IARC Screening Group for her help in thepreparation of the manuscript.

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HPV Screening for Cervical Cancer in Rural India

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