Trend of HPV 16/18 Genotypes in Cervical Intraepithelial Neoplasia Grade 3: Data for 2007–2018

Abstract

Aim In the post-vaccination era, the starting age and time intervals of cervical screening could change (older age and longer screening intervals). This scenario may be achieved by significantly reducing human papillomavirus (HPV) 16/18 prevalence (genotypes included in the current vaccines). In this regard, assessing the trend over time of these HPV infections in high-grade cervical lesions can provide information on the objective. The present study aimed to evaluate the trend of HPV 16/18 over the years 2007–2018 in women with cervical intraepithelial neoplasia (CIN) grade 3. Methods This is a retrospective multi-institutional study including HPV genotyped and unvaccinated women under 30 with CIN3. The sample was divided into the following periods: 2007–2010, 2011–2014, 2015–2018. HPV genotypes were grouped in genotypes 16/18, genotypes 31/33/35/52/58/67 (genetically related to HPV16), genotypes 39/45/59/68/70 (genetically related to HPV18), genotypes 31/33/45/52/58 (high-risk types included in the nonavalent vaccine), possibly carcinogenic HPV (genotypes 26/30/53/67/70/73/82/85), low-risk HPV (genotypes 6/11/40/42/43/44/54/55/61). The trend between periods and HPV genotypes was measured using the Cochran–Armitage test for trend. Results The final analysis included 474 participants. HPV 16/18 prevalence decreased significantly over the years (77.8% vs 68.9% vs 66.0%, respectively, Ptrend=0.027). Possibly carcinogenic HPV (genotypes 26/30/53/67/70/73/82/85) showed a significant negative prevalence trend over time (4.9% vs 1.1% vs 1.3%, respectively, Ptrend=0.046). Finally, there was a significant positive trend over the years for high-risk HPV genotypes 31/33/45/52/58 in women under 25 (9.9% vs 17.0% vs 24.0%, respectively, Ptrend=0.048). Conclusion The prevalence of CIN3 lesions related to HPV 16/18 genotypes decreased over time from 2007 to 2018. These data highlight a herd effect of the HPV vaccine. However, fifteen years after HPV vaccine introduction, we are still a long way from herd immunity. The increase in high-risk types 31/33/45/52/58 will need to be reassessed when the nonavalent vaccine impact will be more reliable.

Prevalence and Distribution of Human Papillomavirus Genotypes (1997–2019) and Their Association With Cervical Cancer and Precursor Lesions in Women From Southern Mexico

“…Worldwide, HPV-16 and HPV-18 contribute to over 70% of all cervical cancer cases. HPV types 31,33,35,45,52, and 58 cause approximately 20% of cervical cancer cases worldwide. (12) The prevalence of HPV-16 and/or HPV-18 among women with no intraepithelial lesion (No-IL) is 3.9%, with low-grade squamous intraepithelial lesions (LSIL) is 25.8%, with high-grade squamous intraepithelial lesions (HSIL) is 51.9%.…”

Which is the best management for women with normal cervical cytologic findings despite positivity for non-16/18 high risk human papillomaviruses?

“…According to the literature, vaccination will not fully avert an increase in colposcopy referrals and the detection of preneoplasia in the first 2–3 years of HPV-based screening. Given the herd effect of the HPV vaccine, the amount is thought to be reduced after 5–6 years, and then by approximately 20% ( 12 , 58 ). It is also predicted that the increase in HR types 31/33/45/52/58 needs to be re-evaluated once the nanovalent vaccine effect becomes more reliable ( 12 ).…”

“…Given the herd effect of the HPV vaccine, the amount is thought to be reduced after 5–6 years, and then by approximately 20% ( 12 , 58 ). It is also predicted that the increase in HR types 31/33/45/52/58 needs to be re-evaluated once the nanovalent vaccine effect becomes more reliable ( 12 ). Consequently, because the effect of vaccination on colposcopies and cervical preneoplasia will be gradual, ways of delivering a more personalized schedule by applying risk stratification and thus improving the identification of precancerous lesions and cancer are worth exploring.…”

“…The significance of HPV genotyping in the early detection of preneoplasia has been confirmed in some regions ( 10 ), and the introduction of the HR-HPV genotyping assay could improve the detection of early-stage HSIL, thus extending the time interval to retest women who are NILM beyond 1 year ( 10 ). Possible changes in the distribution of HPV genotypes have been observed in the post-vaccination era ( 11 ); likewise, the prevalence of HSIL associated with HPV16/18 has decreased over the years ( 12 ). Consequently, it is estimated that the national rollout of HPV vaccination will reduce the number of colposcopies by 10% within the first 3–4 years in developed countries ( 12 ).…”

“…Possible changes in the distribution of HPV genotypes have been observed in the post-vaccination era ( 11 ); likewise, the prevalence of HSIL associated with HPV16/18 has decreased over the years ( 12 ). Consequently, it is estimated that the national rollout of HPV vaccination will reduce the number of colposcopies by 10% within the first 3–4 years in developed countries ( 12 ). However, due to multiple barriers, HPV vaccines remain limited in low- and middle-income countries (particularly in Africa and Asia) ( 13 ).…”