Introduction

HIV and cervical cancer are intersecting epidemics that disproportionately affect one of the most vulnerable populations in the world: women in low- and middle-income countries (LMICs). Historically, the disparity in cervical cancer risk for women in LMICs has been due to the lack of organized screening and prevention programmes. In recent years, this risk has been augmented by the severity of the HIV epidemic in LMICs. HIV-positive women are at increased risk for developing cervical precancer and cancer, and while the introduction of antiretroviral therapy has dramatically improved life expectancies among HIV-positive women it has not been shown to improve cancer-related outcomes. Therefore, an increasing number of HIV-positive women are living in LMICs with limited or no access to cervical cancer screening programmes. In this commentary, we describe the gaps in cervical cancer prevention, the state of evidence for integrating cervical cancer prevention into HIV programmes and future directions for programme implementation and research.

Discussion

Despite the biologic, behavioural and demographic overlap between HIV and cervical cancer, cervical cancer prevention has for the most part been left out of sexual and reproductive health (SRH) services for HIV-positive women. Lower cost primary and secondary prevention strategies for cervical cancer are becoming more widely available in LMICs, with increasing evidence for their efficacy and cost-effectiveness. Going forward, cervical cancer prevention must be considered a part of the essential package of SRH services for HIV-positive women. Effective cervical cancer prevention programmes will require a coordinated response from international policymakers and funders, national governments and community leaders. Leveraging the improvements in healthcare infrastructure created by the response to the global HIV epidemic through integration of services may be an effective way to make an impact to prevent cervical cancer among HIV-positive women, but more work remains to determine optimal approaches.

Conclusions

Cervical cancer prevention is an essential part of comprehensive HIV care. In order to ensure maximal impact and cost-effectiveness, implementation strategies for screening programmes must be adapted and rigorously evaluated through a framework that includes equal participation with policymakers, programme planners and key stakeholders in the target communities.

Introduction

HIV-infected women may have higher rates of recurrent cervical precancer after treatment. Knowledge about rates and predictors of recurrence could impact guidelines and program planning, especially in low-resource settings.

Methods

In this prospective cohort study in Western Kenya, we followed HIV-infected women at 6 and 12 months after treatment for cervical intraepithelial neoplasia 2 or greater (CIN2+) after treatment with loop electrosurgical excision procedure (LEEP). All women underwent follow-up colposcopy with biopsy as indicated for the diagnosis of CIN2+. We calculated the incidence and predictors of primary disease recurrence after treatment.

Results

Among the 284 women who underwent LEEP and had at least 1 follow-up visit, there were 37 (13%) cases of CIN2+ detected by 12-month follow-up. Four (10.8%) of the recurrences were invasive cancer, all stage IA1. The 6- and 12-month rates of recurrence were 13.7 and 12.8 cases per 100 person-years of follow-up, respectively. Antiretroviral therapy use did not significantly impact the rate of recurrence (hazard ratio: 1.24, 95% confidence interval: 0.59 to 2.79). The only significant predictor of recurrence in the multivariate analysis was CD4(+) nadir <200 cells per cubic millimeter (adjusted hazard ratio: 3.14, 95% confidence interval: 1.22 to 8.08).

Discussion

The overall rate of treatment failure within a year of LEEP was low in this cohort of HIV-infected women. Among the women with recurrence, there was a significant amount of invasive cancer. The relatively high rate of cancer after treatment suggests that HIV-infected women merit continued close follow-up after treatment.

HIV and cervical cancer are intersecting epidemics in many low-resource settings, yet there are few accurate estimates of the scope of this public health challenge. To understand disease prevalence and risk factors for cervical intraepithelial neoplasia 2 or greater (CIN2+), we conducted a cross-sectional study of women undergoing cervical cancer screening as part of routine HIV care in Kisumu, Kenya. Women were offered screening with visual inspection with acetic acid, followed by confirmation with colposcopy and biopsy as needed. Univariable and multivariable analyses were carried out to determine clinical and demographic predictors of prevalent CIN2+. Among 3,241 women screened, 287 (9%) had an initial diagnosis of biopsy-confirmed CIN2+. On multivariable analysis, combined oral contraceptives remained significantly associated with detection of CIN2+ among women on HAART (AOR 1.84, CI 1.20-2.82), and not on HAART (AOR 1.72, 95% CI 1.08-2.73), while use of a progesterone implant was associated with increased detection of CIN2+ (AOR 9.43, 95% CI 2.85-31.20) only among women not on HAART. CD4+ nadir over 500 cells/mm(3) was associated with reduced detection of CIN2+ (AOR 0.61, CI 0.38, 0.97) in the overall group, but current CD4+ was only associated with reduced detection of CIN2+ among women not on HAART (AOR 0.42, CI 0.22, 0.80). In conclusion, a history of less severe immunosuppression appeared to reduce the risk of CIN2+ detection, but current CD4+ count was significant only in non-HAART users. The association of CIN2+ with hormonal contraception should be explored more in prospective studies designed to better control for confounding factors.

HIV-infected women are at increased risk for recurrence of cervical dysplasia after treatment. Short-term recurrence rates may reflect treatment efficacy and therefore impact screening protocols and follow-up planning. We conducted a prospective study of 297 HIV-infected women undergoing loop electrosurgical excision procedure for cervical intraepithelial neoplasia 2+ (CIN2+) in an HIV clinic in Kisumu, Kenya. By 6 months after the procedure, 20 (7.1%) of women had recurrent CIN2+. Recurrence was significantly associated with CD4 nadir but not with highly active antiretroviral therapy use. Longer-term follow-up of this cohort will illustrate the potential impact of highly active antiretroviral therapy and immune status on CIN2/3 disease recurrence.

Background

The incidence of cervical cancer in Kenya is among the highest in the world. Few Kenyan women are able to access screening, thus fueling the high cervical cancer burden. Self-collected human papilloma Virus (HPV) tests, administered during community-health campaigns in rural areas may be a way to expand access to screening.

Methods

In December 2015, we carried out a four-day community health campaign (CHC) to educate participants about cervical cancer prevention and offer self-administered HPV screening. Community enumeration, outreach and mobilization preceded the CHC. Samples were sent to Migori County Hospital for HPV DNA testing using careHPV Test Kits. Women were notified of results through their choice of short message service (SMS), phone call, home visit or clinic visit. HPV positive women were referred for cryotherapy following a screen-and-treat strategy.

Results

Door-to-door enumeration identified approximately 870 eligible women in Ngodhe Community in Migori County. Among the 267 women attending the campaign, 255 women enrolled and collected samples: 243 tests were successfully resulted and 12 were indeterminate. Of the 243 resulted tests, 47 (19%) were positive for HPV, with young age being the only significant predictor of positivity. In multivariate analysis, each additional year of age conferred about a 4% decrease in the odds of testing positive (95% CI 0.1 to 7%, p = 0.046). Just over three-quarters of all women (195/255), were notified of their results. Those who were unable to be reached were more likely to prefer receiving results from clinic (54/60, 90%) and were less likely to have mobile phones (24/60, 73%). Although 76% of HPV positive women were notified of their results, just half (51%) of those testing positive presented for treatment. HPV positive women who successfully accessed the treatment facility did not differ from their non-presenting counterparts by demographics, health history, desired route of notification or access to a mobile phone.

Conclusion

Nearly a third of eligible women in Ngodhe Community attended the CHC and were screened for cervical cancer. Nearly all women who attended the CHC underwent cervical cancer screening by self-collected HPV tests. Three-quarters of all participants received results, but just half of HPV positive participants presented for treatment in a timely fashion, suggesting that linkage to treatment remains a major challenge.

Trial registration

NCT02124252 , Registered 25 April 2014.

Objective

To determine the prevalence of invasive cervical cancer (ICC) and assess access to, and outcomes of, treatment for ICC among HIV-infected women in Kisumu, Kenya.

Methods

We performed a retrospective chart review to identify women diagnosed with ICC between October 2007 and June 2012, and to examine the impact of a change in the referral protocol. Prior to June 2009, all women with ICC were referred to a regional hospital. After this date, women with stage IA1 disease were offered treatment with loop electrosurgical excision procedure (LEEP) in-clinic.

Results

Of 4308 women screened, 58 (1.3%) were diagnosed with ICC. The mean age at diagnosis was 34years (range, 22-50years). Fifty-four (93.1%) women had stage IA1 disease, of whom 36 (66.7%) underwent LEEP, 7 (12.9%) had a total abdominal hysterectomy, and 11 (20.4%) had unknown or no treatment. At 6, 12, and 24months after LEEP, 8.0% (2/25), 25.0% (6/24), and 41.2% (7/17) of women had a recurrence of cervical intraepithelial neoplasia 2 or worse, respectively.

Conclusion

Most HIV-positive women diagnosed with ICC through screening had early-stage disease. The introduction of LEEP in-clinic increased access to treatment; however, recurrence was high, indicating the need for continued surveillance.

Visual inspection with acetic acid (VIA) is becoming a more widely recommended and implemented screening tool for cervical cancer prevention programs in low-resource settings. Many of these settings have a high prevalence of HIV-infected women. We carried out a cross-sectional validation study to define the sensitivity, specificity and predictive values of VIA among HIV-infected women. Women enrolled in HIV care at the Family AIDS Care and Education Services clinic in Kisumu, Kenya, were recruited for participation. All participants underwent VIA followed by colposcopy performed by a second blinded clinician. At colposcopy, lesions suspicious for cervical intraepithelial neoplasia 2 or greater (CIN2+) were biopsied. Disease status was determined by final histopathologic diagnosis in women who underwent biopsies. A satisfactory colposcopy with no lesions was considered a negative result. From October 2010 to June 2012, 1,432 women underwent VIA and colposcopy. A total of 514 (35.7%) women had a positive VIA, and 179 (12.2%) had CIN2+ confirmed by colposcopically directed biopsy. Sensitivity, specificity, positive and negative predictive values of VIA for CIN2+ were 86.6, 71.6, 30.3 and 97.4%, respectively. Specificity, but not sensitivity, increased with older age. Among older women, sensitivity was affected by CD4+ count and use of antiretroviral therapy. Although they are impacted by age and immune status, test characteristics for VIA among HIV-infected women are similar to what has been reported for general populations. Recommendations to use VIA as a screening tool should not vary by HIV status.

Objective

To determine the optimal strategy for cervical cancer screening in women with human immunodeficiency virus (HIV) infection by comparing two strategies: visual inspection of the cervix with acetic acid (VIA) and VIA followed immediately by visual inspection with Lugol's iodine (VIA/VILI) in women with a positive VIA result.

Methods

Data from a cervical cancer screening programme embedded in two HIV clinic sites in western Kenya were evaluated. Women at a central site underwent VIA, while women at a peripheral site underwent VIA/VILI. All women positive for cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) on VIA and/or VILI had a confirmatory colposcopy, with a biopsy if necessary. Overall test positivity, positive predictive value (PPV) and the CIN 2+ detection rate were calculated for the two screening methods, with biopsy being the gold standard.

Findings

Between October 2007 and October 2010, 2338 women were screened with VIA and 1124 with VIA/VILI. In the VIA group, 26.4% of the women tested positive for CIN 2+; in the VIA/VILI group, 21.7% tested positive (P < 0.01). Histologically confirmed CIN 2+ was detected in 8.9% and 7.8% (P = 0.27) of women in the VIA and VIA/VILI groups, respectively. The PPV of VIA for biopsy-confirmed CIN 2+ in a single round of screening was 35.2%, compared with 38.2% for VIA/VILI (P = 0.41).

Conclusion

The absence of any differences between VIA and VIA/VILI in detection rates or PPV for CIN 2+ suggests that VIA, an easy testing procedure, can be used alone as a cervical cancer screening strategy in low-income settings.

Objective

A biomarker with increased specificity for cervical dysplasia compared with human papillomavirus (HPV) testing would be an attractive option for cervical cancer screening among HIV-infected women in resource-limited settings. p16(INK4a) has been explored as a biomarker for screening in general populations.

Design

A 2-year cross-sectional study.

Setting

2 large HIV primary care clinics in western Kenya.

Participants

1054 HIV-infected women in western Kenya undergoing cervical cancer screening as part of routine HIV care from October 2010 to November 2012.

Interventions

Participants underwent p16(INK4a) specimen collection and colposcopy. Lesions with unsatisfactory colposcopy or suspicious for cervical intraepithelial neoplasia 2+ (CIN2+; including CIN2/3 or invasive cervical cancer) were biopsied. Following biopsy, disease status was determined by histopathological diagnosis.

Primary and secondary outcome measures

We measured the sensitivity, specificity and predictive values of p16(INK4a) ELISA for CIN2+ detection among HIV-infected women and compared them to the test characteristics of current screening methods used in general as well as HIV-infected populations.

Results

Average p16(INK4a) concentration in cervical samples was 37.4 U/mL. After colposcopically directed biopsy, 127 (12%) women were determined to have CIN2+. Receiver operating characteristic analysis showed an area under the curve of 0.664 for p16(INK4a) to detect biopsy-proven CIN2+. At a p16(INK4a) cut-off level of 9 U/mL, sensitivity, specificity, positive and negative predictive values were 89.0%, 22.9%, 13.6% and 93.8%, respectively. The overall p16(INK4a) positivity at a cut-off level of 9 U/mL was 828 (78.6%) women. There were 325 (30.8%) cases of correct p16(INK4a) prediction to detect or rule out CIN2+, and 729 (69.2%) cases of incorrect p16(INK4a) prediction.

Conclusions

p16(INK4a) ELISA did not perform well as a screening test for CIN2+ detection among HIV-infected women due to low specificity. Our study contributes to the ongoing search for a more specific alternative to HPV testing for CIN2+ detection.