Dr. Nisha Singh, MD (Obstetrics and Gynecology), FICOG.
Clinical Significance of HPV DNA Test as Primary Screening Method for Cervical Cancer in India.
Cervical cancer is the second most common cancer in India and the fourth most common cancer affecting women worldwide with a disproportionate mortality occurring in developing countries (Globcon, 2012). HPV is considered as one of the major etiological factors for cervical cancer along with other factors (Neyaz MK, et al. 2010).
Screening for cervical cancer with Pap smear test has become widely accepted. However, a number of problems with cytology test have been described including sensitivity, subjectivity of reading of slides, quality of samples leading to greater number of interpretive errors. HPV DNA testing offers a viable and validated approach for screening and management of women with/ without cytological abnormalities (Cox T, et al. 2006).
Cervical Cancer Elimination:
In November 2020, the World Health Organization (WHO) launched an initiative for cervical cancer elimination by 2030. According to Dr. Tedros Adhanom Ghebreyesus, WHO Director-General, If we don’t act, deaths from cervical cancer will rise by almost 50% by 2040.” The countries on the path towards cervical cancer elimination have three targets to be met by 2030. These are: vaccination, screening and treatment (90% of Girls are fully vaccinated against HPV by the age of 15, 70% of women are screened by high performance tests by 35-45 years of age and 90% of women with CIN (Cervical Intraepithelial Neoplasia) or cervical cancer are treated).
WHO has recently revised their guidelines for cervical cancer screening applicable to all women across the globe. This includes twenty-three recommendations and seven good clinical practice statements. The major change is the recommendation for using HPV DNA test as the primary screening modality in view of the difficulties in maintaining quality assurance with other screening methods. HPV DNA test should be used for screening all women in general population between 30 to 50 years of age.
Screen and Treat Approach:
Under screen and treat approach, positive women who are suitable for ablative procedure are screened. They are then treated and their treatment plan followed up after 12 months. VIA test with 3-5% acetic acid is recommended for deciding eligibility for ablative procedure. Those who screen positive but are not eligible for ablative procedure have to undergo LLETZ (Loop Electrosurgical Excision Procedure). Cases with obvious growth or suspected cancer must be biopsied and managed accordingly.
Women with a negative HPV test should be reassessed after 5-10 years while HIV positive women should be tested every 3-5 years. If screening is done with VIA or cytology and there is no abnormality, these women should be re-screened after 3 years. Cases with ASCUS (Atypical Squamous Cells of Undetermined Significance) should be subjected to immediate triage with HPV DNA testing, which if positive, should be followed by colposcopy. If HPV test is negative, rescreen after 3 years. For cases with abnormality, above ASCUS on cytology should undergo colposcopy.
Screen, Triage and Treat Approach:
Under screen, triage and treat approach, triage may be done with partial genotyping, colposcopy, VIA or cytology as feasible. Those positive for HPV 16/18 or VIA should be taken up for ablative or excisional procedure as per eligibility. VIA triage negative cases with positive HPV DNA should undergo repeat HPV test after two years in general population and one year in HIV positive women. Colposcopy and Cytology triage will be followed as per the respective reports.
Follow-up Tests for a Woman Treated with Ablation or LLETZ:
Follow up is must if a woman is treated with ablation or Loop Electrosurgical Excision Procedure (LLETZ) based on histopathology or without histopathology. It should be done at 12 months, if positive should be retreated with LLETZ followed by retesting within 12 months. Follow up recommendations are same for general population and HIV positive women.
Management of Abnormal Cytology Results:
Management of abnormal cytology results where HPV Test is not available for triage is as follows: Women aged 25-29 years with ASCUS/LSIL should undergo repeat cytology annually twice – If repeats reveal ASCUS or above, colposcopy and biopsy should be done. Colposcopy and biopsy should be done in case of LSIL (Low-grade Squamous Intraepithelial Lesion) in women aged 30-64 years. HSIL (High-grade Squamous Intraepithelial Lesion) should undergo colposcopy with biopsy and endocervical assessment.
HSIL in women desirous of pregnancy should undergo colposcopy and biopsy. If no CIN 2 or 3, cytology and colposcopy must be repeated 6-monthly for 2 years, if no high risk till 2 years then routine age specific follow up must be repeated. If CIN 2/3 persist for 2 years on a 6-monthly follow up, excisional procedure should be done.
In smears showing atypical endometrial cells or abnormal glandular cells, endometrial and endocervical curettage should be done first followed by colposcopy and biopsy.
As per these new guidelines, HPV DNA testing should be made available wherever new screening facilities are being started and the traditional tests like cytology and VIA should gradually be replaced by the same.
HPV Self-sampling:
Can Human Papillomavirus DNA Self-sampling be an Acceptable and Reliable Option for Cervical Cancer Screening in India?
Self-collected HPV DNA testing has been considered as an effective alternative tool among women coming from infrastructural barriers and individual barriers as nature of gynecological examination may be embarrassing and culturally unacceptable for them. Besides this most of the times Indian women do not get time to travel to physician due to having huge responsibility for home and work. In case of self-collected HPV DNA testing could prove itself a boon and it will also decrease out of pocket cost due to no need of traveling to avail these facilities.
HPV self-sampling can increase cervical cancer screening uptake compared with standard of care, with no negative effect on linkage to clinical assessment/treatment (Ogale Y, etal., 2018). HPV Self sampling could be used to increase the participation of non attenders in the cervical cancer screening program during and after COVID-19 pandemic.
Author:
Dr. Nisha Singh, MD (Obstetrics and Gynecology), FICOG.
Unit Head and In-charge, Genital Cancer Control Unit at King George’s Medical College, Lucknow, Uttar Pradesh, India.
January 9, 2022
Edited By:
Dr. Shalini Mukherjee, Ph.D (Molecular Biology), University of Manitoba, Winnipeg, Manitoba, Canada.
Scientific Editor at Aabir Bio-Services Foundation
Reference:
1. International Agency for Research on Cancer (IARC), World Health Organization (WHO). GLOBOCAN 2012: estimated cancer incidence, mortality and prevalence worldwide in 2012: cancer fact sheets: cervical cancer. Lyon: IARC; 2014.
2. Neyaz MK, Hussain S, Hassan MI, Das BC, Husain Bharadwaj M. Novel missense mutation in FHIT gene: interpreting the effect in HPV-mediated cervical cancer in Indian women. Mol Cell Biochem. 2010; 335:53–58.
3. Cox T, Cuzick J. HPV DNA testing in cervical cancer screening: from evidence to policies. Gynecol Oncol. 2006; 103(1):8–11.
4. Cervical cancer: an NCD we can overcome. Speech by WHO Director-General, 18 May 2018. Geneva: World Health Organization; 2018 (https://www.who.int/dg/speeches/detail/cervical-cancer-an-ncd-we-can-overcome, accessed 2 October 2020).
5. Yasmin Ogale, Ping Teresa Yeh, Caitlin E Kennedy, Igor Toskin and Manjulaa Narasimhan, Self-collection of samples as an additional approach to deliver testing services for sexually transmitted infections: a systematic review and meta-analysis. http://orcid.org/0000-0002-7425-0382.