Diagnostic Techniques for Cervical Cancer (Human Papillomavirus) Detection

Cervical Cancer is one of the most common cancers among women worldwide. Every year, around 14 million women are diagnosed with cervical cancer, with an estimated 8 million deaths. One-fourth of the worldwide burden of cervical cancer is borne by India alone (Bobdey et al., 2016). Cervical cancer is caused due to the persistent infection with the oncogenic Human Papillomavirus (HPV) (Di Paola et al., 2017). This is a sexually transmitted virus that causes vulvar cancer, vaginal cancer, penile cancer, anal cancer, and rectal cancer, among other malignancies.

HPV is divided into two categories:
1. High risk HPV
2. Low risk HPV

HPV 16 and HPV 18 are high-risk HPV types that are responsible for the majority (70%) of cervical cancer occurrences worldwide. The HPV types 31, 33, 35,45,52 and 58 account for approx. 20% of cervical cancers (Eklund et al., 2010a).

Risk Factors (Lobo et al., 2017):
Risk factors of cervical cancer include:
a) Early sexual activity: Early sexual activity increases the risk of cervical cancer and sexually transmitted diseases.
b) Multiple sex partners: having sex with many partners increases the risk of developing HPV infection.
c) Other sexually transmitted infections (STIs). Other STIs, like gonorrhoea, chlamydia, HIV/AIDS, and syphilis, enhances the risk of HPV infection.
d) A weakened immune system. The likelihood of developing cervical cancer increases in immunocompromised (week immune system) people.

Stages of Cervical Cancer (Bhatla et al., 2018):
Cervical cancer has four stages:
Stage 1: This is the earliest stage of cancer. In this stage, cancer is confined to cervix only. Lymph nodes and other body parts are not affected.
Stage 2: The cancer has spread beyond the uterus, but not to the lower third of the vaginal canal or the pelvic wall.
Stage 3: The malignancy has spread to the pelvis and to the lower part of the vagina. It may be blocking the transfer of urine from the kidneys to the bladder. Kidneys become dysfunctional.
Stage 4: The disease has spread to other organs like the lungs, bones, liver.

Laboratory Diagnosis:
Cervical cancer can be detected by:
1. Pap Smear:
Also known as the pap test. In this, method cervix is screened for the presence of precancerous and cancerous cells. Infections with human papilloma virus are self-curable. Only an untreated chronic infection may turn into cervical cancer after many years (Tsikouras et al., n.d.).
In pap smear, outer cells of cervix are collected and examined under a microscope to look for abnormalities. This is a widely used method for early detection of precancer and cervical cancer. Pap test however has some limitations like, insufficient samples received and false negative test results (Eklund et al., 2010b).

2. Liquid Based Cytology (LBC):
This is a microscopic evaluation technique similar to the Pap Smear test except that the sample is collected using a brush which is then placed in the LBC container which has special media for cell preservation and transportation. The Pap Smear test is now replaced with the LBC method as this technique yields a far better picture of the cells and the diagnosis can be made by the pathologist with greater confidence. Additional benefit of LBC is that the same sample can be used further for molecular testing and confirmation thereby avoiding the need for re-sampling.

3. Molecular Diagnosis:
The current gold standard for detection of cervical cancer is identification of HPV DNA or RNA using polymerase chain reaction (PCR). This method of detection offers a high sensitivity and specificity (Tsikouras et al., n.d.). The presence of cancer cells in the cervical samples can be identified by amplification of the single stranded viral RNA using reverse transcriptase (RT) PCR (Tsikouras et al., n.d.).



1 Bhatla, N., Aoki, D., Sharma, D.N., Sankaranarayanan, R., 2018. Cancer of the cervix uteri. Int J Gynecol Obstet 143, 22–36. https://doi.org/10.1002/ijgo.12611

2 Bobdey, S., Sathwara, J., Jain, A., Balasubramaniam, G., 2016. Burden of cervical cancer and role of screening in India. Indian Journal of Medical and Paediatric Oncology 37, 278–285. https://doi.org/10.4103/0971-5851.195751

3 Di Paola, M., Sani, C., Clemente, A.M., Iossa, A., Perissi, E., Castronovo, G., Tanturli, M., Rivero, D., Cozzolino, F., Cavalieri, D., Carozzi, F., De Filippo, C., Torcia, M.G., 2017. Characterization of cervico-vaginal microbiota in women developing persistent high-ris Human Papillomavirus infection. Sci Rep 7, 10200. https://doi.org/10.1038/s41598-017-09842-6

4 Eklund, C., Zhou, T., Dillner, J., 2010a. Global Proficiency Study of Human Papillomavirus Genotyping. J Clin Microbiol 48, 4147–4155. https://doi.org/10.1128/JCM.00918-10

5 Lobo, R.A., Gershenson, D.M., Lentz, G.M., Valea, F.A., 2017. Comprehensive gynecology, 7th edition. ed, ClinicalKey. Elsevier, Philadelphia.

6 Tsikouras, P., Zervoudis, S., Manav, B., Tomara, E., Romanidis, C., Bothou, A., Galazios, G., n.d. Cervical cancer: screening, diagnosis and staging